NSCLC, Non Small Cell Lung Cancer, RCC, Renal Cell Cancer, Pancreatic Cancer, Urothelial Cancer, Head and Neck Cancer, DLBCL, Diffused Large B Cell Lymphoma, MSS, Microsatellite Stable Colon Cancer, TNBC, Triple Negative Breast Cancer, Melanoma, mCRPC, Metastatic Castration Resistant Prostate Cancer
Conditions
Keywords
Immunotherapy, A2aR, PDR001, NIR178, NSCLC, solid tumors
Brief summary
The purpose of this phase 2 study is to evaluate the efficacy and safety of NIR178 in combination with PDR001 in multiple solid tumors and diffuse large B-cell lymphoma (DLBCL) and further explore schedule variations of NIR178 to optimize immune activation through inhibition of A2aR.
Detailed description
This is an open-label multi-part, phase II study evaluating the combination of NIR178 and PDR001 in patients with advanced solid tumors and diffuse large B cell lymphoma (DLBCL). The study has three parts: * Part 1: Multi-arm Bayesian adaptive signal finding design in solid tumors and diffuse large B cell lymphoma (DLBCL) with continuous dosing of NIR178 in combination with PDR001. * Part 2: Exploration of continuous and intermittent NIR178 schedules in combination with PDR001 in patients with advanced non-small cell lung cancer (NSCLC). * Part 3: Further evaluation of optimal intermittent or continuous schedule of NIR178 in combination with PDR001 (if selected based on results of Part 2). As of protocol amendment 6, Part 3 explored the safety and pharmacokinetics of the film-coated tablet (FCT) formulation of NIR178 continuous dosing in combination with PDR001 in tiple negative breast cancer (TNBC) patients. In addition, a separate safety run-in part was conducted in Japan in order to adequately characterize the safety and pharmacokinetic profiles of NIR178 as a single-agent and in combination with PDR001. Patients enrolled in this study received NIR178 either twice daily (BID) continuously or based on the assigned intermittent schedule within 60 minutes prior to PDR001 infusion. PDR001 400 mg was administered via IV infusion over 30 minutes once every 4 weeks. Each treatment cycle was 28 days. Patients enrolled in the Japanese safety run-in part received NIR178 as single agent for the first cycle (28 days). If the patients completed Cycle 1 without experiencing dose limiting toxicities (DLTs), they initiated combination therapy with PDR001 starting Cycle 2 onwards, and continued at the same dose of NIR178. An additional cohort in the Japanese safety run-in part of the study received NIR178 in combination with PDR001 starting with Cycle 1. If the patients complete Cycle 1 without experiencing DLTs, they continued to receive combination treatment. Patients received treatment with the combination until disease progression (assessed by investigator per immune-related response criteria (iRECIST) or Cheson 2014), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment.
Interventions
DRUGNIR178
NIR178, a new, non-xanthine based compound, is a potent oral adenosine A2a receptor against antagonist being developed by Novartis. NIR178 was administered orally twice daily (BID) as a capsule (Part 1, Part 2 and Japanese safety run-in) and as a film-coated table (Part 3). There were up to 3 dose levels assessed: 80, 160 and 240 mg. Three alternative dosing schedules were evaluated: continuous (Part 1, Part 2, Part 3, Japanese safety run-in), 2 weeks on/2 weeks off (Part 2) and 1 week on/1 week off (Part 2). Each cycle consisted of 28 days.
DRUGPDR001
PDR001 is a human monoclonal antibody (MAb) administered on Day 1 of each cycle. PDR001 400 mg was administered via intravenous (i.v.) infusion over 30 minutes every 4 weeks (Q4W).
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1, Part 3 and the Japanese safety run-in part were not randomized. In Part 2, patients were randomized to one of the 3 treatment arms in a ratio of 1:1:1.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients ≥18 years of age. For Japan only: written consent is necessary both from the patient and his/her legal representative if he/she is under the age of 20 years. * Histologically documented advanced or metastatic solid tumors or lymphomas Part 1: histologically confirmed renal cell carcinoma (RCC), pancreatic cancer, urothelial cancer, head and neck cancer, diffuse large B-cell lymphoma (DLBCL), microsatellite stable (MSS) colon cancer, triple negative breast cancer (TNBC), melanoma, metastatic castration resistant prostate cancer (mCRPC) Part 2: histologically confirmed diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be a predominant histology Part 3: histologically confirmed diagnosis of selected advanced/metastatic malignancies. Part 3 will be opened to further assess TNBC patients with a PD-L1 SP-142 IC score of 0 (\<1%). A second tumor group will be considered for Part 3 after completion of Part 1. * Patient (except for those participating in Japanese safety run-in) must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and again during therapy on this study. * Safety run-in part in Japanese patients can enroll any tumor type included in part 1, 2 and 3. The collection of recent sample is permitted under the following conditions (both must be met): Biopsy was collected ≤ 6 months before 1st dose of study treatment and available at the site. No immunotherapy was given to the patient since collection of biopsy. \- Part 1 - 3 only: Patients (other than those with DLBCL) must previously have received at least 1 and no more than 3 prior lines of therapy for their disease (with the exception of IO-pretreated cutaneous melanoma, HNSCC and RCC), unless considered inappropriate for the patient (e.g. safety concern, label contraindication): Patients with NSCLC must have received a prior platinum-based combination. Patients with EGFR positive NSCLC with a T790M mutation must have progressed on osimertinib or discontinued due to toxicity. Patients with head and neck cancer must have received a prior platinum-containing regimen. Patients with bladder cancer must have received a prior platinum-containing regimen or be ineligible for cisplatin. Patients with renal cell carcinoma must have received a prior VEGF tyrosine kinase inhibitor (TKI). Patients with MSS colorectal cancer must have received (or be intolerant to) prior therapy with fluoropyrimidine-oxaliplatin- and irinotecan- based regimens. Patients with triple negative breast cancer:. Part 1: must have received a prior taxane-containing regimen Part 3: should have received no more than 2 prior lines of therapy including taxane-based chemotherapy and should have a known PD-L1 status as per local available testing as determined by VENTANA PD-L1 SP142 Assay with IC score of 0 (\<1%) Patients with DLBCL should be limited to those with no available therapies of proven clinical benefit Patients should have had prior autologous hematopoietic stem cell transplantation (auto-HSCT) or determined to be ineligible for auto-HSCT. Patients with melanoma: BRAF V600E wild type patients: must have received anti-PD-1/PD-L1 single agent, or in combination with anti-CTLA-4 therapy BRAF V600E mutant patients: must have received prior anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy. In addition, subjects must have received prior BRAF V600E inhibitor therapy, either single-agent or in combination with a MEK inhibitor Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC): * Of the 1-3 prior lines of therapy, patients must have received and failed at least one line of treatment after emergence of castration resistant disease * Patients must not have received prior immunotherapy (previous immune checkpoint inhibitors; single agent and/or combination therapy with anti-CTLA-4, anti-PD-1, anti-PD-L1), except for NSCLC patients enrolled in part 3 and Japanese safety run-in part. * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral computer tomography (CT) scan, Magnetic Resonance Imaging (MRI), or calipers by clinical exam.
Exclusion criteria
* Ongoing or prior treatment with A2aR inhibitors. Patients previously treated with A2aR inhibitors for non-oncologic indications (e.g. Parkinson's disease) may be considered for enrollment on a case by case basis. * Current or prior use of immunosuppressive medication within 28 days before the first dose of PDR001, with the exception of intranasal/inhaled corticosteroids or systemic corticosteroids at physiological doses (not exceeding equivalent of 10 mg/day of prednisone) * History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of study drug and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease * Active or prior documented autoimmune disease within the past 2 years. Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. * More than 3 prior lines of therapy except for Japanese safety run-in part. * History of interstitial lung disease or non-infectious pneumonitis * Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 6 weeks is indicated as washout period. For patients receiving anticancer immunotherapies, 4 weeks is indicated as the washout period. GnRH therapy to maintain effective testosterone suppression levels is allowed for mCRPC patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | Up to 3.9 years | ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Part 1: Overall Response Rate (ORR) Per Cheson 2014 for DLBCL | Up to 2.5 years | ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL). For Cheson 2014 criteria, CR= Target nodes/nodal masses must regress to ≤1.5 cm in longest diameter (LDi), no extralymphatic sites of disease, absent non-measured lesions, organ enlargement regress to normal, no new lesions, and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative); PR= ≥50% decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes, absent or regressed non-measured lesions, spleen must have regressed by \>50% in length beyond normal, and no new lesions. |
| Part 2: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | Up to 4.7 years | ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Part 3: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | Up to 0.5 years | ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Mean Percentage Change in PSA From Baseline | Baseline, up to 0.8 years | Prostate-specific antigen (PSA) levels were assessed in serum. Rising PSA is generally a manifestation of progression of prostate cancer. |
| Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | Up to 3.9 years | DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST). |
| Part 1: Disease Control Rate (DCR) Per Cheson 2014 for DLBCL | Up to 2.5 years | DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL). |
| Part 2: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | Up to 4.7 years | DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. |
| Part 2: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | Up to 4.7 years | DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST). |
| Part 3: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | Up to 0.5 years | DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. |
| Part 3: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | Up to 0.5 years | DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST). |
| Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | Up to 3.9 years | DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors | Up to 3.9 years | DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 1: Duration Of Response (DOR) Per Cheson 2014 for DLBCL | Up to 2.5 years | DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per Cheson 2014 criteria for DLBCL. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 2: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | Up to 4.7 years | DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 2: Duration Of Response (DOR) Per iRECIST for Solid Tumors | Up to 4.7 years | DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 3: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | Up to 0.5 years | DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 3: Duration Of Response (DOR) Per iRECIST for Solid Tumors | Up to 0.5 years | DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | Up to 3.9 years | PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | Up to 3.9 years | PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 1: Progression-Free Survival (PFS) Per Cheson 2014 for DLBCL | Up to 2.5 years | PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per Cheson 2014 for DLBCL. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 2: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | Up to 4.7 years | PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 2: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | Up to 4.7 years | PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 3: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | Up to 0.5 years | PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 3: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | Up to 0.5 years | PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan. |
| Part 1: 2-year Overall Survival (OS) | 2 years | OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan (SAP). |
| Part 2: 2-year Overall Survival (OS) | 2 years | OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan. |
| Part 3: 2-year Overall Survival (OS) | 2 years | OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan. |
| Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days. | The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy. |
| Part 2: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days. | The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy. |
| Part 3: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days. | The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy. |
| Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Up to 4 years (Part 1), 4.8 years (Part 2) and 0.6 years (Part 3) | Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration. |
| Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3) | Number of participants with at least one dose reduction of NIR178 and number of participants with at least one dose interruption of NIR178. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule. |
| Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3) | Number of participants with at least one dose reduction of PDR001 and number of participants with at least one dose interruption of PDR001. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule. Dose reductions were not permitted for PDR001. |
| Part 1, 2 and 3: Dose Intensity of NIR178 | Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3) | Dose intensity of NIR178 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days. |
| Part 1, 2 and 3: Dose Intensity of PDR001 | Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3) | Dose intensity of PDR001 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and then multiplied by 28 days. |
| All Study Parts: Maximum Observed Serum Concentration (Cmax) of PDR001 | First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days | PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose. |
| Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Up to approximately 5 years | PDR001 immunogenicity was evaluated in serum samples. Patient anti-drug antibodies (ADA) status was defined as follows: * ADA-negative at baseline: ADA-negative sample at baseline * ADA-positive at baseline: ADA-positive sample at baseline * ADA-negative post-baseline: ADA-negative sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples * Treatment-reduced ADA-positive: ADA-positive sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples * Treatment-induced ADA-positive: ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample * Treatment-boosted ADA-positive: ADA-positive sample at baseline and at least 1 treatment-boosted ADA-positive sample * ADA-inconclusive: patient who does not qualify for any of the above definitions or a patient for which the baseline sample is missing |
| Japan Safety Run-in: Number of Participants With Dose-Limiting Toxicities (DLTs) | 28 days | A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 28 days of treatment with NIR178 as single agent or in combination with PDR001 during the Japan safety run-in part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher. |
| Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Up to 0.7 years | Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration. |
| All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days | Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose. |
| All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days | Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations. |
| All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days | PK parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation. |
| All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days | NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose. |
| All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days | NJI765 is a NIR178 metabolite. Pharmacokinetic (PK) parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations. |
| Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | Up to 3.9 years | DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. |
| All Study Parts: Time to Reach Maximum Serum Concentration (Tmax) of PDR001 | First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days | PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations. |
| All Study Parts: Area Under the Serum Concentration-time Curve From Time Zero to 28 Days Post Dose (AUC0-28day) of PDR001 | First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days | PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-28day calculation. |
| All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days | NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation. |
| Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | Up to 3.9 years | ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST). |
| Part 2: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | Up to 4.7 years | ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST). |
| Part 3: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | Up to 0.5 years | ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST). |
Countries
Argentina, Australia, Austria, Belgium, Czechia, France, Germany, Italy, Japan, Netherlands, Singapore, Spain, Switzerland, Taiwan, United States
Participant flow
Recruitment details
Participants took part in 21 investigative sites in 15 countries.
Pre-assignment details
The screening period began once patients had signed the study informed consent. Screening evaluations had to be completed within 21 days prior to the first dose of treatment except for the radiological tumor assessment which had to be performed within 28 days prior to the first dose. After screening, the treatment period started on Cycle 1 Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: RCC naïve 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with renal cell carcinoma (RCC) who had not been previously treated with immuno-oncology therapy | 11 |
| Part 1: RCC naïve 240 mg NIR178 240 mg twice daily continuous in combination with PDR001 in patients with renal cell carcinoma (RCC) who had not been previously treated with immuno-oncology therapy | 12 |
| Part 1: RCC Pre 240 mg NIR178 240 mg twice daily continuous in combination with PDR001 in patients with renal cell carcinoma (RCC) who had been pretreated with immuno-oncology therapy | 11 |
| Part 1: Pancreatic 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with pancreatic cancer | 14 |
| Part 1: Urothelial 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with urothelial cancer | 14 |
| Part 1: H-N naïve 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with squamous cell carcinoma of head and neck (HNSCC) who had not been previously treated with immuno-oncology therapy | 15 |
| Part 1: H-N Pre 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with squamous cell carcinoma of head and neck (HNSCC) who had been pretreated with immuno-oncology therapy | 11 |
| Part 1: H-N Pre 240 mg NIR178 240 mg twice daily continuous in combination with PDR001 in patients with squamous cell carcinoma of head and neck (HNSCC) who had been pretreated with immuno-oncology therapy | 12 |
| Part 1: MSS CRC wt 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with microsatellite stable colorectal cancer (MSS CRC) with RAS wildtype | 27 |
| Part 1: MSS CRC mu 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with microsatellite stable colorectal cancer (MSS CRC) with RAS mutant | 29 |
| Part 1: MSS CRC Unk 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with microsatellite stable colorectal cancer (MSS CRC) with unknown RAS status | 2 |
| Part 1: TNBC 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with triple negative breast cancer (TNBC) | 30 |
| Part 1: Melanoma naïve 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with cutaneous melanoma who had not been previously treated with immuno-oncology therapy | 3 |
| Part 1: Melanoma Pre 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with cutaneous melanoma who had been pretreated with immuno-oncology therapy | 13 |
| Part 1: DLBCL 160 mg NIR178 160 mg twice daily continuous in combination with PDR001 in patients with diffuse large B-cell lymphoma (DLBCL) | 13 |
| Part 1: DLBCL 240 mg NIR178 240 mg twice daily continuous in combination with PDR001 in patients with diffuse large B-cell lymphoma (DLBCL) | 6 |
| Part 1: mCRPC 240 mg NIR178 240 mg twice daily continuous in combination with PDR001 in patients with metastatic castration resistant prostate cancer (mCRPC) | 15 |
| Part 2: NSCLC 160 mg Cont NIR178 160 mg twice daily continuous in combination with PDR001 in patients with non-small cell lung cancer (NSCLC) | 22 |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off NIR178 160 mg twice daily 2 weeks on/2 weeks off in combination with PDR001 in patients with non-small cell lung cancer (NSCLC) | 20 |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off NIR178 160 mg twice daily 1 week on/1 week off in combination with PDR001 in patients with non-small cell lung cancer (NSCLC) | 20 |
| Part 3: TNBC 160 mg Cont NIR178 160 mg twice daily continuous in combination with PDR001 in patients with triple negative breast cancer (TNBC) | 6 |
| JSR: 80 mg Cont NIR178 80 mg twice daily continuous in combination with PDR001 (starting Cycle 2 Day 1) in the Japan safety run-in | 3 |
| JSR: 160 mg Cont NIR178 160 mg twice daily continuous in combination with PDR001 (starting Cycle 2 Day 1) in the Japan safety run-in | 3 |
| JSR: 240 mg Cont NIR178 140 mg twice daily continuous in combination with PDR001 (starting Cycle 1 Day 1) in the Japan safety run-in | 3 |
| Total | 315 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 0 | 0 | 2 | 1 | 1 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 2 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 1 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Patient/guardian Decision | 0 | 0 | 1 | 1 | 1 | 2 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 1 | 3 | 4 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 3 | 5 | 0 | 3 | 2 | 0 | 0 | 0 | 4 | 2 | 0 | 4 | 0 | 0 | 2 | 1 | 1 | 2 | 1 | 3 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 7 | 7 | 9 | 10 | 11 | 10 | 9 | 8 | 19 | 23 | 2 | 24 | 3 | 11 | 9 | 5 | 10 | 14 | 13 | 14 | 6 | 3 | 3 | 3 |
Baseline characteristics
| Characteristic | Part 1: RCC naïve 160 mg | Part 1: RCC naïve 240 mg | Part 1: RCC Pre 240 mg | Part 1: Pancreatic 160 mg | Part 1: Urothelial 160 mg | Part 1: H-N naïve 160 mg | Part 1: H-N Pre 160 mg | Part 1: H-N Pre 240 mg | Part 1: MSS CRC wt 160 mg | Part 1: MSS CRC mu 160 mg | Part 1: MSS CRC Unk 160 mg | Part 1: TNBC 160 mg | Part 1: Melanoma naïve 160 mg | Part 1: Melanoma Pre 160 mg | Part 1: DLBCL 160 mg | Part 1: DLBCL 240 mg | Part 1: mCRPC 240 mg | Part 2: NSCLC 160 mg Cont | Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 3: TNBC 160 mg Cont | JSR: 80 mg Cont | JSR: 160 mg Cont | JSR: 240 mg Cont | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 10.86 | 60.0 years STANDARD_DEVIATION 11.96 | 60.6 years STANDARD_DEVIATION 8.54 | 60.4 years STANDARD_DEVIATION 8.98 | 66.9 years STANDARD_DEVIATION 9.63 | 61.6 years STANDARD_DEVIATION 7.13 | 59.4 years STANDARD_DEVIATION 9.05 | 60.2 years STANDARD_DEVIATION 7.07 | 56.5 years STANDARD_DEVIATION 9.04 | 58.1 years STANDARD_DEVIATION 11.21 | 46.0 years STANDARD_DEVIATION 15.56 | 49.8 years STANDARD_DEVIATION 10.81 | 50.3 years STANDARD_DEVIATION 20.65 | 54.2 years STANDARD_DEVIATION 14.87 | 55.0 years STANDARD_DEVIATION 18.65 | 61.5 years STANDARD_DEVIATION 13.1 | 68.3 years STANDARD_DEVIATION 8.14 | 65.0 years STANDARD_DEVIATION 9.02 | 61.8 years STANDARD_DEVIATION 9.51 | 64.2 years STANDARD_DEVIATION 8.94 | 58.5 years STANDARD_DEVIATION 16.16 | 61.3 years STANDARD_DEVIATION 10.69 | 57.0 years STANDARD_DEVIATION 9.54 | 44.3 years STANDARD_DEVIATION 8.33 | 59.5 years STANDARD_DEVIATION 11.59 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 8 Participants | 0 Participants | 0 Participants | 8 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 4 Participants | 6 Participants | 2 Participants | 11 Participants | 13 Participants | 12 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 78 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 7 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 21 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 3 Participants | 10 Participants | 13 Participants | 5 Participants | 14 Participants | 9 Participants | 12 Participants | 20 Participants | 23 Participants | 2 Participants | 21 Participants | 1 Participants | 13 Participants | 7 Participants | 0 Participants | 13 Participants | 10 Participants | 7 Participants | 7 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 200 Participants |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 2 Participants | 6 Participants | 5 Participants | 2 Participants | 3 Participants | 3 Participants | 9 Participants | 8 Participants | 1 Participants | 30 Participants | 1 Participants | 3 Participants | 7 Participants | 3 Participants | 0 Participants | 7 Participants | 7 Participants | 8 Participants | 6 Participants | 3 Participants | 1 Participants | 1 Participants | 119 Participants |
| Sex: Female, Male Male | 8 Participants | 12 Participants | 9 Participants | 8 Participants | 9 Participants | 13 Participants | 8 Participants | 9 Participants | 18 Participants | 21 Participants | 1 Participants | 0 Participants | 2 Participants | 10 Participants | 6 Participants | 3 Participants | 15 Participants | 15 Participants | 13 Participants | 12 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 196 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk | EG027 affected / at risk | EG028 affected / at risk | EG029 affected / at risk | EG030 affected / at risk | EG031 affected / at risk | EG032 affected / at risk | EG033 affected / at risk | EG034 affected / at risk | EG035 affected / at risk | EG036 affected / at risk | EG037 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 11 | 6 / 23 | 10 / 14 | 6 / 14 | 8 / 26 | 4 / 12 | 22 / 58 | 9 / 30 | 7 / 16 | 9 / 13 | 2 / 6 | 2 / 15 | 6 / 22 | 4 / 20 | 6 / 20 | 4 / 6 | 2 / 3 | 0 / 3 | 1 / 3 | 3 / 7 | 7 / 17 | 3 / 4 | 4 / 8 | 12 / 18 | 4 / 8 | 22 / 36 | 12 / 21 | 8 / 9 | 2 / 4 | 3 / 4 | 7 / 13 | 8 / 16 | 9 / 16 | 7 / 14 | 1 / 2 | 0 / 0 | 0 / 0 | 1 / 1 |
| other Total, other adverse events | 10 / 11 | 22 / 23 | 14 / 14 | 14 / 14 | 25 / 26 | 12 / 12 | 52 / 58 | 29 / 30 | 14 / 16 | 13 / 13 | 5 / 6 | 14 / 15 | 22 / 22 | 16 / 20 | 17 / 20 | 6 / 6 | 3 / 3 | 2 / 3 | 3 / 3 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 3 / 11 | 7 / 23 | 9 / 14 | 7 / 14 | 16 / 26 | 5 / 12 | 28 / 58 | 14 / 30 | 4 / 16 | 7 / 13 | 0 / 6 | 5 / 15 | 11 / 22 | 9 / 20 | 7 / 20 | 3 / 6 | 2 / 3 | 1 / 3 | 1 / 3 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Part 1: Overall Response Rate (ORR) Per Cheson 2014 for DLBCL
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL). For Cheson 2014 criteria, CR= Target nodes/nodal masses must regress to ≤1.5 cm in longest diameter (LDi), no extralymphatic sites of disease, absent non-measured lesions, organ enlargement regress to normal, no new lesions, and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative); PR= ≥50% decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes, absent or regressed non-measured lesions, spleen must have regressed by \>50% in length beyond normal, and no new lesions.
Time frame: Up to 2.5 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected lymphoma group defined in the study protocol for efficacy assessment: DLBCL 160 mg
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Overall Response Rate (ORR) Per Cheson 2014 for DLBCL | 15.4 percentage of participants |
Primary
Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to 3.9 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected advanced solid tumors groups defined in the study protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg and mCRPC 240 mg
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 27.3 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 25.0 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 0 percentage of participants |
| Part 1: Pancreatic 160 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 0 percentage of participants |
| Part 1: Urothelial 160 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 7.1 percentage of participants |
| Part 1: H-N naïve 160 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 13.3 percentage of participants |
| Part 1: H-N Pre 160 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 0 percentage of participants |
| Part 1: MSS CRC wt 160 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 0 percentage of participants |
| Part 1: MSS CRC mu 160 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 3.4 percentage of participants |
| Part 1: TNBC 160 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 10.0 percentage of participants |
| Part 1: Melanoma Pre 160 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 0 percentage of participants |
| Part 1: mCRPC 240 mg | Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 0 percentage of participants |
Primary
Part 2: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to 4.7 years
Population: All patients from Part 2 who were randomized to the study treatment dosing schedule.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 9.1 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 2: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 0 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 2: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 10.0 percentage of participants |
Primary
Part 3: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1. For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to 0.5 years
Population: All patients from Part 3 who received at least 1 full or partial dose of assigned combination of study drugs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors | 16.7 percentage of participants |
Secondary
All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178
PK parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Population: Patients in the pharmacokinetic analysis set (PAS) who received NIR178 and had an available value for the outcome measure at each timepoint. PAS consists of all patients who received one of the planned treatments, provided at least one PK parameter and did not vomit within 4 hours after dosing with NIR178. Patients from the same ethnicity (Non-Japanese, Japanese) treated with the same formulation (capsule, tablet) at the same NIR178 dose level are pooled together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 1 (all regimens) | 295 hr*ng/mL | Geometric Coefficient of Variation 198.3 |
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 7 (1 wk-on/1 wk-off) | 1260 hr*ng/mL | Geometric Coefficient of Variation 63.2 |
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 14 (2 wk-on/2 wk-off) | 1680 hr*ng/mL | Geometric Coefficient of Variation 94.4 |
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 28 (continuous) | 918 hr*ng/mL | Geometric Coefficient of Variation 187.5 |
| Part 1: RCC naïve 240 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 1 (all regimens) | 487 hr*ng/mL | Geometric Coefficient of Variation 126.3 |
| Part 1: RCC naïve 240 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 28 (continuous) | 1620 hr*ng/mL | Geometric Coefficient of Variation 147.9 |
| Part 1: RCC Pre 240 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 28 (continuous) | 938 hr*ng/mL | Geometric Coefficient of Variation 412.2 |
| Part 1: RCC Pre 240 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 1 (all regimens) | 232 hr*ng/mL | Geometric Coefficient of Variation 437.4 |
| Part 1: Pancreatic 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 28 (continuous) | 697 hr*ng/mL | Geometric Coefficient of Variation 131.8 |
| Part 1: Pancreatic 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 1 (all regimens) | 170 hr*ng/mL | Geometric Coefficient of Variation 124.9 |
| Part 1: Urothelial 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 1 (all regimens) | 63.3 hr*ng/mL | Geometric Coefficient of Variation 88 |
| Part 1: Urothelial 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 28 (continuous) | 242 hr*ng/mL | Geometric Coefficient of Variation 13.5 |
| Part 1: H-N naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 28 (continuous) | 12800 hr*ng/mL | — |
| Part 1: H-N naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178 | Cycle 1 Day 1 (all regimens) | 550 hr*ng/mL | — |
Secondary
All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite)
NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Population: Patients in the pharmacokinetic analysis set (PAS) who received NIR178 and had an available value for the outcome measure at each timepoint. PAS consists of all patients who received one of the planned treatments, provided at least one PK parameter and did not vomit within 4 hours after dosing with NIR178. Patients from the same ethnicity (Non-Japanese, Japanese) treated with the same formulation (capsule, tablet) at the same NIR178 dose level are pooled together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 98.2 hr*ng/mL | Geometric Coefficient of Variation 87.1 |
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 7 (1 wk-on/1 wk-off) | 243 hr*ng/mL | Geometric Coefficient of Variation 57.5 |
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 14 (2 wk-on/2 wk-off) | 288 hr*ng/mL | Geometric Coefficient of Variation 23.7 |
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 214 hr*ng/mL | Geometric Coefficient of Variation 76.6 |
| Part 1: RCC naïve 240 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 382 hr*ng/mL | Geometric Coefficient of Variation 43.7 |
| Part 1: RCC naïve 240 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 122 hr*ng/mL | Geometric Coefficient of Variation 75.6 |
| Part 1: RCC Pre 240 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 226 hr*ng/mL | Geometric Coefficient of Variation 147 |
| Part 1: RCC Pre 240 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 77.1 hr*ng/mL | Geometric Coefficient of Variation 35.9 |
| Part 1: Urothelial 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 117 hr*ng/mL | Geometric Coefficient of Variation 68.2 |
| Part 1: Urothelial 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 277 hr*ng/mL | Geometric Coefficient of Variation 69 |
| Part 1: H-N naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 362 hr*ng/mL | — |
| Part 1: H-N naïve 160 mg | All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 119 hr*ng/mL | — |
Secondary
All Study Parts: Area Under the Serum Concentration-time Curve From Time Zero to 28 Days Post Dose (AUC0-28day) of PDR001
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-28day calculation.
Time frame: First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days
Population: Patients in the pharmacokinetic analysis set (PAS) who received PDR001 and had an available value for the outcome measure at each timepoint. PAS consists of all patients who received one of the planned treatments, provided at least one PK parameter and did not vomit within 4 hours after dosing with NIR178. Patients from the same ethnicity (Non-Japanese, Japanese) treated at the same PDR001 dose level are pooled together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Serum Concentration-time Curve From Time Zero to 28 Days Post Dose (AUC0-28day) of PDR001 | First dose (Cycle 1 Day 1 or Cycle 2 Day 1) | 1140 day*µg/mL | Geometric Coefficient of Variation 31.2 |
| Part 1: RCC naïve 160 mg | All Study Parts: Area Under the Serum Concentration-time Curve From Time Zero to 28 Days Post Dose (AUC0-28day) of PDR001 | Cycle 3 Day 1 | 2030 day*µg/mL | Geometric Coefficient of Variation 41.3 |
| Part 1: RCC naïve 240 mg | All Study Parts: Area Under the Serum Concentration-time Curve From Time Zero to 28 Days Post Dose (AUC0-28day) of PDR001 | First dose (Cycle 1 Day 1 or Cycle 2 Day 1) | 1110 day*µg/mL | Geometric Coefficient of Variation 13.9 |
Secondary
All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178
Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Population: Patients in the pharmacokinetic analysis set (PAS) who received NIR178 and had an available value for the outcome measure at each timepoint. PAS consists of all patients who received one of the planned treatments, provided at least one PK parameter and did not vomit within 4 hours after dosing with NIR178. Patients from the same ethnicity (Non-Japanese, Japanese) treated with the same formulation (capsule, tablet) at the same NIR178 dose level are pooled together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 129 ng/mL | Geometric Coefficient of Variation 335 |
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 14 (2 wk-on/2 wk-off) | 392 ng/mL | Geometric Coefficient of Variation 212.7 |
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 7 (1 wk-on/1 wk-off) | 576 ng/mL | Geometric Coefficient of Variation 83.1 |
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 28 (continuous) | 297 ng/mL | Geometric Coefficient of Variation 291.4 |
| Part 1: RCC naïve 240 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 160 ng/mL | Geometric Coefficient of Variation 247.8 |
| Part 1: RCC naïve 240 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 28 (continuous) | 622 ng/mL | Geometric Coefficient of Variation 154.3 |
| Part 1: RCC Pre 240 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 28 (continuous) | 723 ng/mL | Geometric Coefficient of Variation 295.5 |
| Part 1: RCC Pre 240 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 75.1 ng/mL | Geometric Coefficient of Variation 382.3 |
| Part 1: Pancreatic 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 28 (continuous) | 311 ng/mL | Geometric Coefficient of Variation 91.5 |
| Part 1: Pancreatic 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 81.8 ng/mL | Geometric Coefficient of Variation 99.9 |
| Part 1: Urothelial 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 28 (continuous) | 167 ng/mL | Geometric Coefficient of Variation 40.9 |
| Part 1: Urothelial 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 30.1 ng/mL | Geometric Coefficient of Variation 32.9 |
| Part 1: H-N naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 28 (continuous) | 3760 ng/mL | Geometric Coefficient of Variation 39.6 |
| Part 1: H-N naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 234 ng/mL | Geometric Coefficient of Variation 70.9 |
Secondary
All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite)
NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Population: Patients in the pharmacokinetic analysis set (PAS) who received NIR178 and had an available value for the outcome measure at each timepoint. PAS consists of all patients who received one of the planned treatments, provided at least one PK parameter and did not vomit within 4 hours after dosing with NIR178. Patients from the same ethnicity (Non-Japanese, Japanese) treated with the same formulation (capsule, tablet) at the same NIR178 dose level are pooled together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 25.5 ng/mL | Geometric Coefficient of Variation 85.2 |
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 7 (1 wk-on/1 wk-off) | 62.9 ng/mL | Geometric Coefficient of Variation 39.4 |
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 14 (2 wk-on/2 wk-off) | 71.3 ng/mL | Geometric Coefficient of Variation 43.3 |
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 42.6 ng/mL | Geometric Coefficient of Variation 82.2 |
| Part 1: RCC naïve 240 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 33.7 ng/mL | Geometric Coefficient of Variation 64.2 |
| Part 1: RCC naïve 240 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 77.3 ng/mL | Geometric Coefficient of Variation 49.9 |
| Part 1: RCC Pre 240 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 54.1 ng/mL | Geometric Coefficient of Variation 102.4 |
| Part 1: RCC Pre 240 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 20.1 ng/mL | Geometric Coefficient of Variation 99.2 |
| Part 1: Pancreatic 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 45.6 ng/mL | Geometric Coefficient of Variation 74 |
| Part 1: Urothelial 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 25.9 ng/mL | Geometric Coefficient of Variation 77 |
| Part 1: Urothelial 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 53.9 ng/mL | Geometric Coefficient of Variation 64.2 |
| Part 1: H-N naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 111 ng/mL | Geometric Coefficient of Variation 36.6 |
| Part 1: H-N naïve 160 mg | All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 28.5 ng/mL | Geometric Coefficient of Variation 99.9 |
Secondary
All Study Parts: Maximum Observed Serum Concentration (Cmax) of PDR001
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Time frame: First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days
Population: Patients in the pharmacokinetic analysis set (PAS) who received PDR001 and had an available value for the outcome measure at each timepoint. PAS consists of all patients who received one of the planned treatments, provided at least one PK parameter and did not vomit within 4 hours after dosing with NIR178. Patients from the same ethnicity (Non-Japanese, Japanese) treated at the same PDR001 dose level are pooled together.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Serum Concentration (Cmax) of PDR001 | Cycle 3 Day 1 | 126 µg/mL | Geometric Coefficient of Variation 37.4 |
| Part 1: RCC naïve 160 mg | All Study Parts: Maximum Observed Serum Concentration (Cmax) of PDR001 | First dose (Cycle 1 Day 1 or Cycle 2 Day 1) | 93.2 µg/mL | Geometric Coefficient of Variation 30.8 |
| Part 1: RCC naïve 240 mg | All Study Parts: Maximum Observed Serum Concentration (Cmax) of PDR001 | First dose (Cycle 1 Day 1 or Cycle 2 Day 1) | 85.0 µg/mL | Geometric Coefficient of Variation 12.8 |
| Part 1: RCC naïve 240 mg | All Study Parts: Maximum Observed Serum Concentration (Cmax) of PDR001 | Cycle 3 Day 1 | 119 µg/mL | — |
Secondary
All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178
Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Population: Patients in the pharmacokinetic analysis set (PAS) who received NIR178 and had an available value for the outcome measure at each timepoint. PAS consists of all patients who received one of the planned treatments, provided at least one PK parameter and did not vomit within 4 hours after dosing with NIR178. Patients from the same ethnicity (Non-Japanese, Japanese) treated with the same formulation (capsule, tablet) at the same NIR178 dose level are pooled together.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 28 (continuous) | 2.00 hours |
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 2.00 hours |
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 7 (1 wk-on/1 wk-off) | 1.45 hours |
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 14 (2 wk-on/2 wk-off) | 1.97 hours |
| Part 1: RCC naïve 240 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 2.13 hours |
| Part 1: RCC naïve 240 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 28 (continuous) | 2.02 hours |
| Part 1: RCC Pre 240 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 28 (continuous) | 1.52 hours |
| Part 1: RCC Pre 240 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 1.50 hours |
| Part 1: Pancreatic 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 28 (continuous) | 1.43 hours |
| Part 1: Pancreatic 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 1.50 hours |
| Part 1: Urothelial 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 28 (continuous) | 1.45 hours |
| Part 1: Urothelial 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 1.50 hours |
| Part 1: H-N naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 1 (all regimens) | 3.00 hours |
| Part 1: H-N naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178 | Cycle 1 Day 28 (continuous) | 2.87 hours |
Secondary
All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite)
NJI765 is a NIR178 metabolite. Pharmacokinetic (PK) parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
Time frame: Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Population: Patients in the pharmacokinetic analysis set (PAS) who received NIR178 and had an available value for the outcome measure at each timepoint. PAS consists of all patients who received one of the planned treatments, provided at least one PK parameter and did not vomit within 4 hours after dosing with NIR178. Patients from the same ethnicity (Non-Japanese, Japanese) treated with the same formulation (capsule, tablet) at the same NIR178 dose level are pooled together.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 7 (1 wk-on/1 wk-off) | 1.50 hours |
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 14 (2 wk-on/2 wk-off) | 1.98 hours |
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 2.00 hours |
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 2.00 hours |
| Part 1: RCC naïve 240 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 2.08 hours |
| Part 1: RCC naïve 240 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 2.10 hours |
| Part 1: RCC Pre 240 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 0.750 hours |
| Part 1: RCC Pre 240 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 2.10 hours |
| Part 1: Pancreatic 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 2.23 hours |
| Part 1: Urothelial 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 1.95 hours |
| Part 1: Urothelial 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 1.45 hours |
| Part 1: H-N naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 1 (all regimens) | 3.00 hours |
| Part 1: H-N naïve 160 mg | All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite) | Cycle 1 Day 28 (continuous) | 2.87 hours |
Secondary
All Study Parts: Time to Reach Maximum Serum Concentration (Tmax) of PDR001
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Time frame: First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days
Population: Patients in the pharmacokinetic analysis set (PAS) who received PDR001 and had an available value for the outcome measure at each timepoint. PAS consists of all patients who received one of the planned treatments, provided at least one PK parameter and did not vomit within 4 hours after dosing with NIR178. Patients from the same ethnicity (Non-Japanese, Japanese) treated at the same PDR001 dose level are pooled together.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Serum Concentration (Tmax) of PDR001 | Cycle 3 Day 1 | 1.50 hours |
| Part 1: RCC naïve 160 mg | All Study Parts: Time to Reach Maximum Serum Concentration (Tmax) of PDR001 | First dose (Cycle 1 Day 1 or Cycle 2 Day 1) | 1.50 hours |
| Part 1: RCC naïve 240 mg | All Study Parts: Time to Reach Maximum Serum Concentration (Tmax) of PDR001 | First dose (Cycle 1 Day 1 or Cycle 2 Day 1) | 1.50 hours |
| Part 1: RCC naïve 240 mg | All Study Parts: Time to Reach Maximum Serum Concentration (Tmax) of PDR001 | Cycle 3 Day 1 | 1.65 hours |
Secondary
Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period
Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.
Time frame: Up to 0.7 years
Population: All patients from the Japan safety run-in who received at least 1 dose of NIR178 or PDR001.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: RCC naïve 160 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 2 Participants |
| Part 1: RCC naïve 160 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
| Part 1: RCC naïve 160 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 3 Participants |
| Part 1: RCC naïve 160 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 0 Participants |
| Part 1: RCC naïve 160 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 0 Participants |
| Part 1: RCC naïve 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 1 Participants |
| Part 1: RCC naïve 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
| Part 1: RCC naïve 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 2 Participants |
| Part 1: RCC naïve 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: RCC naïve 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 3 Participants |
| Part 1: RCC naïve 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 1 Participants |
| Part 1: RCC Pre 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 1 Participants |
| Part 1: RCC Pre 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 3 Participants |
| Part 1: RCC Pre 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 1 Participants |
| Part 1: RCC Pre 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: RCC Pre 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 0 Participants |
| Part 1: RCC Pre 240 mg | Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
Secondary
Japan Safety Run-in: Number of Participants With Dose-Limiting Toxicities (DLTs)
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 28 days of treatment with NIR178 as single agent or in combination with PDR001 during the Japan safety run-in part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Time frame: 28 days
Population: All patients in the Japan safety run-in who either met the minimum exposure criterion defined in the protocol and had sufficient safety evaluations, or had experienced a DLT during Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Japan Safety Run-in: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: RCC naïve 240 mg | Japan Safety Run-in: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: RCC Pre 240 mg | Japan Safety Run-in: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Part 1, 2 and 3: Dose Intensity of NIR178
Dose intensity of NIR178 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days.
Time frame: Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
Population: All patients from Part 1, 2 and 3 who received at least 1 dose of NIR178 or PDR001. For the safety endpoints, patients at each study part with the same type of cancer who are treated at the same dose level and dosing schedule are pooled together, independently of the immune-oncology (IO) pretreatment status and RAS mutation status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 316.7 mg/day |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 477.3 mg/day |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 320.0 mg/day |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 295.7 mg/day |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 309.8 mg/day |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 480.0 mg/day |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 320.0 mg/day |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 320.0 mg/day |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 320.0 mg/day |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 320.0 mg/day |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 480.0 mg/day |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 480.0 mg/day |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Dose Intensity of NIR178 | 320.0 mg/day |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Dose Intensity of NIR178 | 160.0 mg/day |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Dose Intensity of NIR178 | 160.0 mg/day |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Dose Intensity of NIR178 | 320.0 mg/day |
Secondary
Part 1, 2 and 3: Dose Intensity of PDR001
Dose intensity of PDR001 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and then multiplied by 28 days.
Time frame: Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
Population: All patients from Part 1, 2 and 3 who received at least 1 dose of NIR178 or PDR001. For the safety endpoints, patients at each study part with the same type of cancer who are treated at the same dose level and dosing schedule are pooled together, independently of the immune-oncology (IO) pretreatment status and RAS mutation status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 394.2 mg/28 days |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 396.2 mg/28 days |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 393.1 mg/28 days |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 398.2 mg/28 days |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Dose Intensity of PDR001 | 400.0 mg/28 days |
Secondary
Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period
Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.
Time frame: Up to 4 years (Part 1), 4.8 years (Part 2) and 0.6 years (Part 3)
Population: All patients from Part 1, 2 and 3 who received at least 1 dose of NIR178 or PDR001. For the safety endpoints, patients at each study part with the same type of cancer who are treated at the same dose level and dosing schedule are pooled together, independently of the immune-oncology (IO) pretreatment status and RAS mutation status.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 3 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 0 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 7 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 10 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 1 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 2 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 16 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 22 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 7 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 9 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 14 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 1 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 9 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 2 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 1 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 14 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 7 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 9 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 15 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 16 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 26 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 2 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 3 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 12 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 5 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 1 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 2 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 9 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 3 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 7 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 34 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 57 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 28 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 1 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 29 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 23 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 11 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 2 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 6 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 0 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 15 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 3 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 2 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 11 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 6 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 13 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 1 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 2 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 5 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 14 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 4 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 2 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 12 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 1 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 6 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 11 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 15 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 22 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 7 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 3 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 14 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 2 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 18 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 9 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 7 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 18 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 0 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related AEs | 4 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 3 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related fatal SAEs | 0 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Fatal SAEs | 0 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs | 6 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Treatment-related SAEs | 0 Participants |
Secondary
Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies
PDR001 immunogenicity was evaluated in serum samples. Patient anti-drug antibodies (ADA) status was defined as follows: * ADA-negative at baseline: ADA-negative sample at baseline * ADA-positive at baseline: ADA-positive sample at baseline * ADA-negative post-baseline: ADA-negative sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples * Treatment-reduced ADA-positive: ADA-positive sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples * Treatment-induced ADA-positive: ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample * Treatment-boosted ADA-positive: ADA-positive sample at baseline and at least 1 treatment-boosted ADA-positive sample * ADA-inconclusive: patient who does not qualify for any of the above definitions or a patient for which the baseline sample is missing
Time frame: Up to approximately 5 years
Population: All patients from Part 1, 2 and 3 who received at least 1 dose of NIR178 or PDR001 and had a determinant baseline immunogenicity (IG) sample and at least 1 determinant post-baseline IG sample for assessing anti-PDR001 antibodies. For the safety endpoints, patients at each study part with the same type of cancer who are treated at the same dose level and dosing schedule are pooled together, independently of the immune-oncology (IO) pretreatment status and RAS mutation status.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 10 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 11 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 1 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 23 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 0 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 23 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 1 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 12 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 11 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 1 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 13 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 12 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 24 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 22 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 2 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 11 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 11 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 0 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 49 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 1 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 3 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 48 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 1 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 2 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 25 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 27 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 2 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 13 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 13 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 0 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 0 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 10 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 10 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 6 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 6 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 11 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 13 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 2 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 21 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 21 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 19 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 14 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 5 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 3 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 14 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 17 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative at baseline | 6 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-reduced ADA-positive | 0 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-boosted ADA-positive | 0 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-inconclusive | 0 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-positive at baseline | 0 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | Treatment-induced ADA-positive | 1 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies | ADA-negative post-baseline | 5 Participants |
Secondary
Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178
Number of participants with at least one dose reduction of NIR178 and number of participants with at least one dose interruption of NIR178. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
Time frame: Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
Population: All patients from Part 1, 2 and 3 who received at least 1 dose of NIR178 or PDR001. For the safety endpoints, patients at each study part with the same type of cancer who are treated at the same dose level and dosing schedule are pooled together, independently of the immune-oncology (IO) pretreatment status and RAS mutation status.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 2 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 6 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 1 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 9 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 0 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 2 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 2 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 8 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 12 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 8 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 3 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 1 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 7 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 20 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 3 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 9 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 3 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 1 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 1 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 3 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 1 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 2 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 5 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 2 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 8 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 5 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 1 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 1 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 4 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose reduction | 0 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178 | At least one dose interruption | 0 Participants |
Secondary
Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001
Number of participants with at least one dose reduction of PDR001 and number of participants with at least one dose interruption of PDR001. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule. Dose reductions were not permitted for PDR001.
Time frame: Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
Population: All patients from Part 1, 2 and 3 who received at least 1 dose of NIR178 or PDR001. For the safety endpoints, patients at each study part with the same type of cancer who are treated at the same dose level and dosing schedule are pooled together, independently of the immune-oncology (IO) pretreatment status and RAS mutation status.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: RCC naïve 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 6 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: RCC naïve 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 7 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: RCC Pre 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 1 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: Pancreatic 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 6 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 9 Participants |
| Part 1: Urothelial 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 1 Participants |
| Part 1: H-N naïve 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: H-N Pre 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 13 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: MSS CRC wt 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 8 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 2 Participants |
| Part 1: MSS CRC mu 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: TNBC 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: Melanoma Pre 160 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 2 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 1: mCRPC 240 mg | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 6 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 4 Participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 2 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose reduction | 0 Participants |
| Part 3: TNBC 160 mg Cont | Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001 | At least one dose interruption | 0 Participants |
Secondary
Part 1: 2-year Overall Survival (OS)
OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan (SAP).
Time frame: 2 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected cancer groups defined in the protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg, DLBCL 160 mg and mCRPC 240 mg
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: 2-year Overall Survival (OS) | 63.6 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 1: 2-year Overall Survival (OS) | 42.1 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 1: 2-year Overall Survival (OS) | 27.3 percentage of participants |
| Part 1: Pancreatic 160 mg | Part 1: 2-year Overall Survival (OS) | NA percentage of participants |
| Part 1: Urothelial 160 mg | Part 1: 2-year Overall Survival (OS) | 36.1 percentage of participants |
| Part 1: H-N naïve 160 mg | Part 1: 2-year Overall Survival (OS) | 33.3 percentage of participants |
| Part 1: H-N Pre 160 mg | Part 1: 2-year Overall Survival (OS) | 15.3 percentage of participants |
| Part 1: MSS CRC wt 160 mg | Part 1: 2-year Overall Survival (OS) | 22.1 percentage of participants |
| Part 1: MSS CRC mu 160 mg | Part 1: 2-year Overall Survival (OS) | 14.3 percentage of participants |
| Part 1: TNBC 160 mg | Part 1: 2-year Overall Survival (OS) | 30.8 percentage of participants |
| Part 1: Melanoma Pre 160 mg | Part 1: 2-year Overall Survival (OS) | NA percentage of participants |
| Part 1: mCRPC 240 mg | Part 1: 2-year Overall Survival (OS) | 23.1 percentage of participants |
| Part 1: mCRPC 240 mg | Part 1: 2-year Overall Survival (OS) | 31.4 percentage of participants |
Secondary
Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue
The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
Time frame: Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days.
Population: All patients from Part 1 who received any study drug, had paired tumor samples, had a valid assessment for the outcome measure and were included in the selected cancer groups defined in the protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg, DLBCL 160 mg and mCRPC 240 mg
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 10.93 CD8 percent marker area | Standard Deviation 14.227 |
| Part 1: RCC naïve 240 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 10.53 CD8 percent marker area | Standard Deviation 12.456 |
| Part 1: RCC Pre 240 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 0.70 CD8 percent marker area | Standard Deviation 2.645 |
| Part 1: Pancreatic 160 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | -0.81 CD8 percent marker area | Standard Deviation 0.537 |
| Part 1: Urothelial 160 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 0.96 CD8 percent marker area | Standard Deviation 1.345 |
| Part 1: H-N naïve 160 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 1.63 CD8 percent marker area | Standard Deviation 2.372 |
| Part 1: H-N Pre 160 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | -0.42 CD8 percent marker area | Standard Deviation 1.477 |
| Part 1: MSS CRC wt 160 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 0.70 CD8 percent marker area | Standard Deviation 1.141 |
| Part 1: MSS CRC mu 160 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | -0.01 CD8 percent marker area | Standard Deviation 1.164 |
| Part 1: TNBC 160 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 4.86 CD8 percent marker area | Standard Deviation 3.751 |
| Part 1: Melanoma Pre 160 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 0.16 CD8 percent marker area | Standard Deviation 0.54 |
| Part 1: mCRPC 240 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 7.84 CD8 percent marker area | — |
| Part 1: mCRPC 240 mg | Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 2.67 CD8 percent marker area | Standard Deviation 4.156 |
Secondary
Part 1: Disease Control Rate (DCR) Per Cheson 2014 for DLBCL
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL).
Time frame: Up to 2.5 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected lymphoma group defined in the study protocol for efficacy assessment: DLBCL 160 mg
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Disease Control Rate (DCR) Per Cheson 2014 for DLBCL | 23.1 percentage of participants |
Secondary
Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 3.9 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected advanced solid tumors groups defined in the study protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg and mCRPC 240 mg
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 63.6 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 66.7 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 18.2 percentage of participants |
| Part 1: Pancreatic 160 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 0 percentage of participants |
| Part 1: Urothelial 160 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 35.7 percentage of participants |
| Part 1: H-N naïve 160 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 40.0 percentage of participants |
| Part 1: H-N Pre 160 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 54.5 percentage of participants |
| Part 1: MSS CRC wt 160 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 25.9 percentage of participants |
| Part 1: MSS CRC mu 160 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 13.8 percentage of participants |
| Part 1: TNBC 160 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 36.7 percentage of participants |
| Part 1: Melanoma Pre 160 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 0 percentage of participants |
| Part 1: mCRPC 240 mg | Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 46.7 percentage of participants |
Secondary
Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
Time frame: Up to 3.9 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected advanced solid tumors groups defined in the study protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg and mCRPC 240 mg
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 54.5 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 66.7 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 18.2 percentage of participants |
| Part 1: Pancreatic 160 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 0 percentage of participants |
| Part 1: Urothelial 160 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 28.6 percentage of participants |
| Part 1: H-N naïve 160 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 40.0 percentage of participants |
| Part 1: H-N Pre 160 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 63.6 percentage of participants |
| Part 1: MSS CRC wt 160 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 25.9 percentage of participants |
| Part 1: MSS CRC mu 160 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 17.2 percentage of participants |
| Part 1: TNBC 160 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 33.3 percentage of participants |
| Part 1: Melanoma Pre 160 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 0 percentage of participants |
| Part 1: mCRPC 240 mg | Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 46.7 percentage of participants |
Secondary
Part 1: Duration Of Response (DOR) Per Cheson 2014 for DLBCL
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per Cheson 2014 criteria for DLBCL. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 2.5 years
Population: All patients from Part 1 for whom best overall response was CR or PR and were included in the selected lymphoma group defined in the study protocol for efficacy assessment: DLBCL 160 mg
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Duration Of Response (DOR) Per Cheson 2014 for DLBCL | NA months |
Secondary
Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 3.9 years
Population: All patients from Part 1 for whom best overall response was iCR or iPR and were included in the selected advanced solid tumors groups defined in the study protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg and mCRPC 240 mg
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
| Part 1: RCC naïve 240 mg | Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
| Part 1: Urothelial 160 mg | Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
| Part 1: H-N naïve 160 mg | Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
| Part 1: MSS CRC mu 160 mg | Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
| Part 1: TNBC 160 mg | Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
Secondary
Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 3.9 years
Population: All patients from Part 1 for whom best overall response was CR or PR and were included in the selected advanced solid tumors groups defined in the study protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg and mCRPC 240 mg
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA months |
| Part 1: RCC naïve 240 mg | Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA months |
| Part 1: Urothelial 160 mg | Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA months |
| Part 1: H-N naïve 160 mg | Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA months |
| Part 1: MSS CRC mu 160 mg | Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA months |
| Part 1: TNBC 160 mg | Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA months |
Secondary
Part 1: Mean Percentage Change in PSA From Baseline
Prostate-specific antigen (PSA) levels were assessed in serum. Rising PSA is generally a manifestation of progression of prostate cancer.
Time frame: Baseline, up to 0.8 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the prostate cancer group defined in the study protocol for efficacy assessment: mCRPC 240 mg
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Mean Percentage Change in PSA From Baseline | 214.46 percentage change in PSA from baseline | Standard Deviation 329.459 |
Secondary
Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 3.9 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected advanced solid tumors groups defined in the study protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg and mCRPC 240 mg
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 36.4 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 25.0 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 0 percentage of participants |
| Part 1: Pancreatic 160 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 0 percentage of participants |
| Part 1: Urothelial 160 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 7.1 percentage of participants |
| Part 1: H-N naïve 160 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 13.3 percentage of participants |
| Part 1: H-N Pre 160 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 0 percentage of participants |
| Part 1: MSS CRC wt 160 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 0 percentage of participants |
| Part 1: MSS CRC mu 160 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 3.4 percentage of participants |
| Part 1: TNBC 160 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 10.0 percentage of participants |
| Part 1: Melanoma Pre 160 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 0 percentage of participants |
| Part 1: mCRPC 240 mg | Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 0 percentage of participants |
Secondary
Part 1: Progression-Free Survival (PFS) Per Cheson 2014 for DLBCL
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per Cheson 2014 for DLBCL. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 2.5 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected lymphoma group defined in the study protocol for efficacy assessment: DLBCL 160 mg
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Progression-Free Survival (PFS) Per Cheson 2014 for DLBCL | 1.7 months |
Secondary
Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 3.9 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected advanced solid tumors groups defined in the study protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg and mCRPC 240 mg
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 8.7 months |
| Part 1: RCC naïve 240 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 7.2 months |
| Part 1: RCC Pre 240 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 1.9 months |
| Part 1: Pancreatic 160 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 1.7 months |
| Part 1: Urothelial 160 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 2.1 months |
| Part 1: H-N naïve 160 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 2.0 months |
| Part 1: H-N Pre 160 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 3.5 months |
| Part 1: MSS CRC wt 160 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 1.8 months |
| Part 1: MSS CRC mu 160 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 1.9 months |
| Part 1: TNBC 160 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 1.8 months |
| Part 1: Melanoma Pre 160 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 1.8 months |
| Part 1: mCRPC 240 mg | Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 3.7 months |
Secondary
Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 3.9 years
Population: All patients from Part 1 who received at least 1 full or partial dose of assigned combination of study drugs and were included in the selected advanced solid tumors groups defined in the study protocol for efficacy assessment: RCC naïve 160 mg, RCC naïve 240 mg, RCC pre 240 mg, pancreatic 160 mg, urothelial 160 mg, H-N naïve 160 mg, H-N pre 160 mg, MSS CRC wt 160 mg, MSS CRC mu 160 mg, TNBC 160 mg, melanoma pre 160 mg and mCRPC 240 mg
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 3.5 months |
| Part 1: RCC naïve 240 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 7.2 months |
| Part 1: RCC Pre 240 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.9 months |
| Part 1: Pancreatic 160 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.7 months |
| Part 1: Urothelial 160 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.9 months |
| Part 1: H-N naïve 160 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 2.0 months |
| Part 1: H-N Pre 160 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 3.5 months |
| Part 1: MSS CRC wt 160 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.7 months |
| Part 1: MSS CRC mu 160 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.9 months |
| Part 1: TNBC 160 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.7 months |
| Part 1: Melanoma Pre 160 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.8 months |
| Part 1: mCRPC 240 mg | Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 3.7 months |
Secondary
Part 2: 2-year Overall Survival (OS)
OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan.
Time frame: 2 years
Population: All patients from Part 2 who were randomized to the study treatment dosing schedule.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: 2-year Overall Survival (OS) | 33.6 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 2: 2-year Overall Survival (OS) | 22.7 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 2: 2-year Overall Survival (OS) | 39.7 percentage of participants |
Secondary
Part 2: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue
The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
Time frame: Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days.
Population: All patients from Part 2 who received any study drug, had paired tumor samples and had a valid assessment for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 3.81 CD8 percent marker area | Standard Deviation 4.551 |
| Part 1: RCC naïve 240 mg | Part 2: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | -2.35 CD8 percent marker area | Standard Deviation 5.586 |
| Part 1: RCC Pre 240 mg | Part 2: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 1.23 CD8 percent marker area | Standard Deviation 2.955 |
Secondary
Part 2: Disease Control Rate (DCR) Per iRECIST for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 4.7 years
Population: All patients from Part 2 who were randomized to the study treatment dosing schedule.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 36.4 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 2: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 45.0 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 2: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 45.0 percentage of participants |
Secondary
Part 2: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
Time frame: Up to 4.7 years
Population: All patients from Part 2 who were randomized to the study treatment dosing schedule.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 36.4 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 2: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 40.0 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 2: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 35.0 percentage of participants |
Secondary
Part 2: Duration Of Response (DOR) Per iRECIST for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 4.7 years
Population: All patients from Part 2 for whom best overall response was iCR or iPR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
| Part 1: RCC naïve 240 mg | Part 2: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
| Part 1: RCC Pre 240 mg | Part 2: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
Secondary
Part 2: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 4.7 years
Population: All patients from Part 2 for whom best overall response was CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA months |
| Part 1: RCC Pre 240 mg | Part 2: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA months |
Secondary
Part 2: Overall Response Rate (ORR) Per iRECIST for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 4.7 years
Population: All patients from Part 2 who were randomized to the study treatment dosing schedule.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 9.1 percentage of participants |
| Part 1: RCC naïve 240 mg | Part 2: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 5.0 percentage of participants |
| Part 1: RCC Pre 240 mg | Part 2: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 15.0 percentage of participants |
Secondary
Part 2: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 4.7 years
Population: All patients from Part 2 who were randomized to the study treatment dosing schedule.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 2.1 months |
| Part 1: RCC naïve 240 mg | Part 2: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 2.2 months |
| Part 1: RCC Pre 240 mg | Part 2: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 2.8 months |
Secondary
Part 2: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 4.7 years
Population: All patients from Part 2 who were randomized to the study treatment dosing schedule.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 2: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 2.0 months |
| Part 1: RCC naïve 240 mg | Part 2: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 2.1 months |
| Part 1: RCC Pre 240 mg | Part 2: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.9 months |
Secondary
Part 3: 2-year Overall Survival (OS)
OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan.
Time frame: 2 years
Population: All patients from Part 3 who received at least 1 full or partial dose of assigned combination of study drugs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: 2-year Overall Survival (OS) | NA percentage of participants |
Secondary
Part 3: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue
The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
Time frame: Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days.
Population: All patients from Part 3 who received any study drug, had paired tumor samples and had a valid assessment for the outcome measure
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue | 0.26 CD8 percent marker area |
Secondary
Part 3: Disease Control Rate (DCR) Per iRECIST for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 0.5 years
Population: All patients from Part 3 who received at least 1 full or partial dose of assigned combination of study drugs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: Disease Control Rate (DCR) Per iRECIST for Solid Tumors | 16.7 percentage of participants |
Secondary
Part 3: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors
DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
Time frame: Up to 0.5 years
Population: All patients from Part 3 who received at least 1 full or partial dose of assigned combination of study drugs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors | 16.7 percentage of participants |
Secondary
Part 3: Duration Of Response (DOR) Per iRECIST for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 0.5 years
Population: All patients from Part 3 for whom best overall response was iCR or iPR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: Duration Of Response (DOR) Per iRECIST for Solid Tumors | NA months |
Secondary
Part 3: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 0.5 years
Population: All patients from Part 3 for whom best overall response was CR or PR
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors | NA months |
Secondary
Part 3: Overall Response Rate (ORR) Per iRECIST for Solid Tumors
ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
Time frame: Up to 0.5 years
Population: All patients from Part 3 who received at least 1 full or partial dose of assigned combination of study drugs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: Overall Response Rate (ORR) Per iRECIST for Solid Tumors | 16.7 percentage of participants |
Secondary
Part 3: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 0.5 years
Population: All patients from Part 3 who received at least 1 full or partial dose of assigned combination of study drugs.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors | 1.6 months |
Secondary
Part 3: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1. PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
Time frame: Up to 0.5 years
Population: All patients from Part 3 who received at least 1 full or partial dose of assigned combination of study drugs.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: RCC naïve 160 mg | Part 3: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors | 1.6 months |
Post Hoc
All-Collected Deaths
On-treatment and post-treatment safety follow-up deaths were collected from first dose of study medication to 150 days after last dose of NIR178+PDR001. Survival follow-up deaths were collected from 151 days after last dose of NIR178+PDR001 until end of study. All deaths refer to the sum of on-treatment and post-treatment safety follow-up deaths plus survival follow-up deaths.
Time frame: On-treatment and safety follow-up (FU) deaths: up to 4.3 years (Part 1), 5.1 years (Part 2), 0.9 years (Part 3) and 0.9 years (JSR). Survival FU deaths: up to 4.3 years (Part 1), 5.1 years (Part 2) and 0.9 years (Part 3) and 0.9 years (JSR)
Population: All patients who received at least one dose of study treatment. Patients at each study part with the same type of cancer who are treated at the same dose level and dosing schedule are pooled together, independently of the immune-oncology (IO) pretreatment status and RAS mutation status.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: RCC naïve 160 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 4 participants |
| Part 1: RCC naïve 160 mg | All-Collected Deaths | All deaths | 7 participants |
| Part 1: RCC naïve 160 mg | All-Collected Deaths | Survival follow-up deaths | 3 participants |
| Part 1: RCC naïve 240 mg | All-Collected Deaths | All deaths | 13 participants |
| Part 1: RCC naïve 240 mg | All-Collected Deaths | Survival follow-up deaths | 7 participants |
| Part 1: RCC naïve 240 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 6 participants |
| Part 1: RCC Pre 240 mg | All-Collected Deaths | All deaths | 13 participants |
| Part 1: RCC Pre 240 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 10 participants |
| Part 1: RCC Pre 240 mg | All-Collected Deaths | Survival follow-up deaths | 3 participants |
| Part 1: Pancreatic 160 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 6 participants |
| Part 1: Pancreatic 160 mg | All-Collected Deaths | Survival follow-up deaths | 4 participants |
| Part 1: Pancreatic 160 mg | All-Collected Deaths | All deaths | 10 participants |
| Part 1: Urothelial 160 mg | All-Collected Deaths | Survival follow-up deaths | 12 participants |
| Part 1: Urothelial 160 mg | All-Collected Deaths | All deaths | 20 participants |
| Part 1: Urothelial 160 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 8 participants |
| Part 1: H-N naïve 160 mg | All-Collected Deaths | Survival follow-up deaths | 4 participants |
| Part 1: H-N naïve 160 mg | All-Collected Deaths | All deaths | 8 participants |
| Part 1: H-N naïve 160 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 4 participants |
| Part 1: H-N Pre 160 mg | All-Collected Deaths | Survival follow-up deaths | 22 participants |
| Part 1: H-N Pre 160 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 22 participants |
| Part 1: H-N Pre 160 mg | All-Collected Deaths | All deaths | 44 participants |
| Part 1: MSS CRC wt 160 mg | All-Collected Deaths | All deaths | 21 participants |
| Part 1: MSS CRC wt 160 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 9 participants |
| Part 1: MSS CRC wt 160 mg | All-Collected Deaths | Survival follow-up deaths | 12 participants |
| Part 1: MSS CRC mu 160 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 7 participants |
| Part 1: MSS CRC mu 160 mg | All-Collected Deaths | Survival follow-up deaths | 8 participants |
| Part 1: MSS CRC mu 160 mg | All-Collected Deaths | All deaths | 15 participants |
| Part 1: TNBC 160 mg | All-Collected Deaths | Survival follow-up deaths | 2 participants |
| Part 1: TNBC 160 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 9 participants |
| Part 1: TNBC 160 mg | All-Collected Deaths | All deaths | 11 participants |
| Part 1: Melanoma Pre 160 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 2 participants |
| Part 1: Melanoma Pre 160 mg | All-Collected Deaths | All deaths | 5 participants |
| Part 1: Melanoma Pre 160 mg | All-Collected Deaths | Survival follow-up deaths | 3 participants |
| Part 1: mCRPC 240 mg | All-Collected Deaths | Survival follow-up deaths | 7 participants |
| Part 1: mCRPC 240 mg | All-Collected Deaths | All deaths | 9 participants |
| Part 1: mCRPC 240 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 2 participants |
| Part 1: mCRPC 240 mg | All-Collected Deaths | All deaths | 14 participants |
| Part 1: mCRPC 240 mg | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 6 participants |
| Part 1: mCRPC 240 mg | All-Collected Deaths | Survival follow-up deaths | 8 participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | All-Collected Deaths | Survival follow-up deaths | 9 participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 4 participants |
| Part 2: NSCLC 160 mg 2wk-on/2wk-off | All-Collected Deaths | All deaths | 13 participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 6 participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | All-Collected Deaths | Survival follow-up deaths | 7 participants |
| Part 2: NSCLC 160 mg 1wk-on/1wk-off | All-Collected Deaths | All deaths | 13 participants |
| Part 3: TNBC 160 mg Cont | All-Collected Deaths | All deaths | 5 participants |
| Part 3: TNBC 160 mg Cont | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 4 participants |
| Part 3: TNBC 160 mg Cont | All-Collected Deaths | Survival follow-up deaths | 1 participants |
| JSR: 80 mg Cont | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 2 participants |
| JSR: 80 mg Cont | All-Collected Deaths | All deaths | 2 participants |
| JSR: 160 mg Cont | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 0 participants |
| JSR: 160 mg Cont | All-Collected Deaths | All deaths | 0 participants |
| JSR: 240 mg Cont | All-Collected Deaths | All deaths | 2 participants |
| JSR: 240 mg Cont | All-Collected Deaths | On-treatment and post-treatment safety follow-up deaths | 1 participants |
| JSR: 240 mg Cont | All-Collected Deaths | Survival follow-up deaths | 1 participants |