Anaplastic Thyroid Cancer, Melanoma, Non-small Sell Lung Cancer (NSCLC), Other Solid Tumors, Triple Negative Breast Cancer
Conditions
Keywords
Phase I/II, PDR001, Checkpoint inhibitor, PD-1, PD-L1, NSCLC
Brief summary
The purpose of this first-in-human study of PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors. By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells.
Detailed description
This study was designed as a phase I/II, multi-center, open-label study starting with a phase I dose escalation part followed by a phase II part. Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups. PDR001 was administered every 2 weeks until patient experienced unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment was discontinued at the discretion of the investigator or the patient.
Interventions
BIOLOGICALPDR001
anti-PD1 antibody
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent must have been obtained prior to any screening procedures * Phase I part: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists. * Phase II part: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed following their last prior therapy, and fit into one of the following groups: * Group 1a and 1b: NSCLC: Patients with NSCLC must have had disease recurrence or progression during or after no more than one prior systemic chemotherapy regimen (platinum doublet-based) for advanced or metastatic disease. Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab). Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). All patients must be tested for EGFR mutational status and, for ALK translocation status if no mutation is detected in EGFR. Patients with ALK translocation-positive NSCLC must have had disease progression following treatment with a corresponding inhibitor and no more than one systemic chemotherapy regimen (platinum doublet-based), in any sequence. * Group 2: Melanoma: All patients must have been tested for BRAF mutations. Patients with V600 mutation positive melanoma must have clinical or radiological evidence of disease progression during or after treatment with a BRAF inhibitor alone or in combination with other agents. * Group 3: Triple negatice breast cancer. * Group 4: Anaplastic thyroid cancer * Patients are not required to have received or progressed on a prior therapy. * Patients must not be at short term risk for life threatening complications (such as airway compromise or bleeding from locoregional or metastatic disease). * Chemoradiation and/or surgery should be considered prior to study entry for those patients with locally advanced disease if those therapies are considered to be in the best interest of the patient. * ECOG Performance Status ≤ 1. * Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy. Patient must be willing to undergo a new tumor biopsy at baseline or at molecular pre-screening if applicable, and during therapy on this study. For patients in the phase II part of the study, exceptions may be granted after documented discussion with Novartis. After a sufficient number of paired biopsies are collected, the decision may be taken to stop the collection of biopsies.
Exclusion criteria
* History of severe hypersensitivity reactions to other mAbs * Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Active infection requiring systemic antibiotic therapy. * HIV infection. * Active HBV or HCV infection. * Patients with ocular melanoma. * 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, 4 weeks washout period. For patients receiving anticancer immunotherapies such as CTLA-4 antagonists, 6 weeks is indicated as the washout period. * Prior PD-1- or PD-L1-directed therapy. * Patients requiring chronic treatment with systemic steroid therapy, other than replacement-dose steroids in the setting of adrenal insufficiency. Topical, inhaled, nasal and ophthalmic steroids are not prohibited. * Patients receiving systemic treatment with any immunosuppressive medication (other than steroids as described above). * Use of any vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment. * Presence of ≥ CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 3) | Estimated the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001. AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. |
| Phase l: Incidence of Dose Limiting Toxicities (DLTs) | 8 months | DLT is defined as an adverse event (AE) 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 cycle of treatment with PDR001 during the dose escalation part of the study for which relationship to study treatment cannot be ruled out, with some exceptions. |
| Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | 61 months | ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required. PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3) | AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1). |
| Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3) | The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) |
| Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3) | The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) |
| Phase I: Presence and/or Concentration of Anti-PDR001 | 42 months | Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment. |
| Phase II: Presence and/or Concentration of Anti-PDR001 | 42 months | Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment. For Treatment -induced ADA-positive, Percentage was based on subjects ADA-negative at baseline. For Treatment-boosted ADA-positive, Percentage was based on subjects ADA-positive at baseline. |
| Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 | 27 months | ORR is the percentage of participants with a best overall response of complete response CR or partial response PR as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. |
| Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 27 months | DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. |
| Phase l: Progression Free Survival (PFS) as Per RECIST v1.1 | 27 months | PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. |
| Phase I: Duration of Response (DOR) as Per RECIST v1.1 | 27 months | DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required; PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required; PD =progression \<= 12 weeks after randomization/start of treatment (and not qualifying for CR, PR or SD). SD = at least 1 SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment |
| Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) | 27 months | ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3) | AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1). |
| Phase l Only: Progression Free Survival (PFS) as Per irRC | 27 months | PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Phase I: Duration of Response (DOR) as Per irRC | 61 Days | DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression \<= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) \> 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug |
| Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 61 months | DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. |
| Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1 | 61 months | PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. |
| Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1 | 61 months | DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. PD = progression \<= start of treatment (and not qualifying for CR, PR or SD). SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. |
| Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC | 61 months | ORR is the percentage of participants with a best overall response CR or PR as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC | 61 months | DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Phase II: Progression Free Survival (PFS) Per irRC | 61 months | PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Phase II: Duration of Response (DOR) Per irRC | 61 months | DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression \<= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) \> 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug |
| Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC | 27 months | DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3) | The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) |
| Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3) | The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) |
Countries
Canada, France, Germany, Hungary, Italy, Lebanon, Netherlands, Norway, Poland, Spain, Taiwan, Thailand, Turkey (Türkiye), United States
Participant flow
Recruitment details
58 patients were analyzed in Phase l and 261 patients were analyzed in Phase II of this study.
Pre-assignment details
The study planned to analyze about 58 patients in Phase I and about 120 patients in Phase II.
Participants by arm
| Arm | Count |
|---|---|
| 1mg/kg q2w Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | 16 |
| 3mg/kg q2w Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | 15 |
| 10mg/kg q2w Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | 11 |
| 3mg/kg q4w Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | 6 |
| 5mg/kg q4w Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | 10 |
| NSCLC 400mg/q4w Phase II: non-small cell cancer patients who took PDR001 400 mg/q4w | 59 |
| Melanoma 400mg/q4w Phase II: Melanoma patients who took PDR001 400 mg/q4w | 61 |
| TNBC 400mg/q4w Phase II: Triple negative breast cancer (TNBC) patients who took PDR001 400 mg/q4w | 40 |
| NSCLC 300mg/q3w Phase II: non-small cell cancer patients who took PDR001 300 mg/q3w | 59 |
| ATC 400 mg/q4w Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w | 42 |
| Total | 319 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase 1 Part | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 Part | Death | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 Part | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 Part | Progressive Disease | 14 | 11 | 7 | 6 | 9 | 0 | 0 | 0 | 0 | 0 |
| Phase 1 Part | Subject/Guardian Decision | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 2 Part | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 3 | 6 | 1 |
| Phase 2 Part | Death | 0 | 0 | 0 | 0 | 0 | 4 | 8 | 4 | 10 | 9 |
| Phase 2 Part | Physician Decision | 0 | 0 | 0 | 0 | 0 | 7 | 9 | 2 | 1 | 3 |
| Phase 2 Part | Progressive disease | 0 | 0 | 0 | 0 | 0 | 43 | 32 | 31 | 39 | 27 |
| Phase 2 Part | Subject/guardian decision | 0 | 0 | 0 | 0 | 0 | 3 | 9 | 0 | 3 | 2 |
Baseline characteristics
| Characteristic | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w | NSCLC 400mg/q4w | 1mg/kg q2w | Melanoma 400mg/q4w | TNBC 400mg/q4w | NSCLC 300mg/q3w | ATC 400 mg/q4w | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized < 65 years | 9 Participants | 8 Participants | 6 Participants | 8 Participants | 33 Participants | 12 Participants | 37 Participants | 29 Participants | 35 Participants | 25 Participants | 202 Participants |
| Age, Customized ≥ 65years | 6 Participants | 3 Participants | 0 Participants | 2 Participants | 26 Participants | 4 Participants | 24 Participants | 11 Participants | 24 Participants | 17 Participants | 117 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 12 Participants | 3 Participants | 23 Participants | 4 Participants | 8 Participants | 4 Participants | 60 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Caucasian | 14 Participants | 8 Participants | 4 Participants | 8 Participants | 42 Participants | 10 Participants | 37 Participants | 32 Participants | 50 Participants | 33 Participants | 238 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 2 Participants | 4 Participants | 23 Participants | 9 Participants | 22 Participants | 40 Participants | 20 Participants | 19 Participants | 150 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 4 Participants | 6 Participants | 36 Participants | 7 Participants | 39 Participants | 0 Participants | 39 Participants | 23 Participants | 169 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 16 | 2 / 15 | 1 / 11 | 5 / 42 | 1 / 6 | 2 / 10 | 3 / 16 | 8 / 58 | 4 / 59 | 4 / 61 | 4 / 40 | 12 / 59 | 11 / 42 | 35 / 261 |
| other Total, other adverse events | 16 / 16 | 15 / 15 | 11 / 11 | 42 / 42 | 6 / 6 | 10 / 10 | 16 / 16 | 58 / 58 | 54 / 59 | 55 / 61 | 37 / 40 | 56 / 59 | 39 / 42 | 241 / 261 |
| serious Total, serious adverse events | 9 / 16 | 7 / 15 | 4 / 11 | 20 / 42 | 2 / 6 | 2 / 10 | 4 / 16 | 24 / 58 | 27 / 59 | 22 / 61 | 18 / 40 | 37 / 59 | 22 / 42 | 126 / 261 |
Outcome results
Primary
Phase l: Incidence of Dose Limiting Toxicities (DLTs)
DLT is defined as an adverse event (AE) 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 cycle of treatment with PDR001 during the dose escalation part of the study for which relationship to study treatment cannot be ruled out, with some exceptions.
Time frame: 8 months
Population: Safety Set: The Safety Set included all subjects from the FAS who received at least one dose of spartalizumab and had at least one valid post-baseline safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg/kg q2w | Phase l: Incidence of Dose Limiting Toxicities (DLTs) | 0 Participants |
| 3mg/kg q2w | Phase l: Incidence of Dose Limiting Toxicities (DLTs) | 0 Participants |
| 10mg/kg q2w | Phase l: Incidence of Dose Limiting Toxicities (DLTs) | 0 Participants |
| 3mg/kg q4w | Phase l: Incidence of Dose Limiting Toxicities (DLTs) | 0 Participants |
| 5mg/kg q4w | Phase l: Incidence of Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required. PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment.
Time frame: 61 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg/kg q2w | Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | 15.3 Percentage of participants |
| 3mg/kg q2w | Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | 27.9 Percentage of participants |
| 10mg/kg q2w | Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | 0.0 Percentage of participants |
| 3mg/kg q4w | Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | 6.8 Percentage of participants |
| 5mg/kg q4w | Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | 19.0 Percentage of participants |
| All Phase II Patients | Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | 14.6 Percentage of participants |
Primary
Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days)
Estimated the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001. AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 3)
Population: Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 1mg/kg q2w | Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) | 270 day*ug/mL | Geometric Coefficient of Variation 52.5 |
| 3mg/kg q2w | Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) | 1150 day*ug/mL | Geometric Coefficient of Variation 51.1 |
| 10mg/kg q2w | Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) | 3110 day*ug/mL | Geometric Coefficient of Variation 33.1 |
| 3mg/kg q4w | Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) | 575 day*ug/mL | Geometric Coefficient of Variation 21.8 |
| 5mg/kg q4w | Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) | 1490 day*ug/mL | Geometric Coefficient of Variation 34.2 |
Secondary
Phase I: Duration of Response (DOR) as Per irRC
DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression \<= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) \> 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug
Time frame: 61 Days
Population: Full analysis set - Dose escalation
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1mg/kg q2w | Phase I: Duration of Response (DOR) as Per irRC | 261.00 days |
| 3mg/kg q2w | Phase I: Duration of Response (DOR) as Per irRC | 55.00 days |
| 10mg/kg q2w | Phase I: Duration of Response (DOR) as Per irRC | 158.00 days |
| 3mg/kg q4w | Phase I: Duration of Response (DOR) as Per irRC | 158.00 days |
Secondary
Phase I: Duration of Response (DOR) as Per RECIST v1.1
DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required; PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required; PD =progression \<= 12 weeks after randomization/start of treatment (and not qualifying for CR, PR or SD). SD = at least 1 SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment
Time frame: 27 months
Population: Full analysis set - Dose escalation
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1mg/kg q2w | Phase I: Duration of Response (DOR) as Per RECIST v1.1 | 261.00 days |
| 3mg/kg q2w | Phase I: Duration of Response (DOR) as Per RECIST v1.1 | 55.00 days |
| 10mg/kg q2w | Phase I: Duration of Response (DOR) as Per RECIST v1.1 | 158.00 days |
| 3mg/kg q4w | Phase I: Duration of Response (DOR) as Per RECIST v1.1 | 158.00 days |
Secondary
Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug.
Time frame: 61 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg/kg q2w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC | 55.9 Percentage of participants |
| 3mg/kg q2w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC | 67.2 Percentage of participants |
| 10mg/kg q2w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC | 22.5 Percentage of participants |
| 3mg/kg q4w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC | 39.0 Percentage of participants |
| 5mg/kg q4w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC | 35.7 Percentage of participants |
| All Phase II Patients | Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC | 46.4 Percentage of participants |
Secondary
Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment.
Time frame: 61 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg/kg q2w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 49.2 Percentage of participants |
| 3mg/kg q2w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 62.3 Percentage of participants |
| 10mg/kg q2w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 20.0 Percentage of participants |
| 3mg/kg q4w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 35.6 Percentage of participants |
| 5mg/kg q4w | Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 31.0 Percentage of participants |
| All Phase II Patients | Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 41.8 Percentage of participants |
Secondary
Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1
DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. PD = progression \<= start of treatment (and not qualifying for CR, PR or SD). SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment.
Time frame: 61 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1mg/kg q2w | Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1 | 5.6 months |
| 3mg/kg q2w | Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1 | 32.0 months |
| 10mg/kg q2w | Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1 | 10.9 months |
| 3mg/kg q4w | Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1 | 22.8 months |
Secondary
Phase II: Duration of Response (DOR) Per irRC
DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression \<= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) \> 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug
Time frame: 61 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1mg/kg q2w | Phase II: Duration of Response (DOR) Per irRC | 5.6 months |
| 3mg/kg q2w | Phase II: Duration of Response (DOR) Per irRC | 32.0 months |
| 10mg/kg q2w | Phase II: Duration of Response (DOR) Per irRC | 10.9 months |
| 3mg/kg q4w | Phase II: Duration of Response (DOR) Per irRC | 22.1 months |
Secondary
Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC
ORR is the percentage of participants with a best overall response CR or PR as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug.
Time frame: 61 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg/kg q2w | Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC | 18.6 Percentage of participants |
| 3mg/kg q2w | Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC | 31.1 Percentage of participants |
| 10mg/kg q2w | Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC | 0.0 Percentage of participants |
| 3mg/kg q4w | Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC | 8.5 Percentage of participants |
| 5mg/kg q4w | Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC | 23.8 Percentage of participants |
| All Phase II Patients | Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC | 17.2 Percentage of participants |
Secondary
Phase II: Presence and/or Concentration of Anti-PDR001
Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment. For Treatment -induced ADA-positive, Percentage was based on subjects ADA-negative at baseline. For Treatment-boosted ADA-positive, Percentage was based on subjects ADA-positive at baseline.
Time frame: 42 months
Population: Immunogenicity incidence Set: The Immunogenicity incidence set includes all subjects in FAS with a determinant baseline immunoglobulin (IG) sample and at least one determinant post-baseline IG sample.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 9 Participants |
| 1mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 9 Participants |
| 1mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 11 Participants |
| 1mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 2 Participants |
| 1mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 34 Participants |
| 1mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 43 Participants |
| 3mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 4 Participants |
| 3mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 2 Participants |
| 3mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 6 Participants |
| 3mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 46 Participants |
| 3mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 2 Participants |
| 3mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 48 Participants |
| 10mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 6 Participants |
| 10mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 23 Participants |
| 10mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 29 Participants |
| 10mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 1 Participants |
| 10mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 4 Participants |
| 10mg/kg q2w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 7 Participants |
| 3mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 41 Participants |
| 3mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 10 Participants |
| 3mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 2 Participants |
| 3mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 12 Participants |
| 3mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 5 Participants |
| 3mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 31 Participants |
| 5mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 29 Participants |
| 5mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 2 Participants |
| 5mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 1 Participants |
| 5mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 6 Participants |
| 5mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 24 Participants |
| 5mg/kg q4w | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 5 Participants |
| All Phase II Patients | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 40 Participants |
| All Phase II Patients | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 190 Participants |
| All Phase II Patients | Phase II: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 26 Participants |
| All Phase II Patients | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 8 Participants |
| All Phase II Patients | Phase II: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 158 Participants |
| All Phase II Patients | Phase II: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 32 Participants |
Secondary
Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment.
Time frame: 61 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1mg/kg q2w | Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1 | 2.7 Percentage of participants |
| 3mg/kg q2w | Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1 | 4.7 Percentage of participants |
| 10mg/kg q2w | Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1 | 1.7 Percentage of participants |
| 3mg/kg q4w | Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1 | 1.9 Percentage of participants |
| 5mg/kg q4w | Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1 | 1.7 Percentage of participants |
Secondary
Phase II: Progression Free Survival (PFS) Per irRC
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug.
Time frame: 61 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1mg/kg q2w | Phase II: Progression Free Survival (PFS) Per irRC | 3.7 Percentage of participants |
| 3mg/kg q2w | Phase II: Progression Free Survival (PFS) Per irRC | 5.4 Percentage of participants |
| 10mg/kg q2w | Phase II: Progression Free Survival (PFS) Per irRC | 1.8 Percentage of participants |
| 3mg/kg q4w | Phase II: Progression Free Survival (PFS) Per irRC | 2.0 Percentage of participants |
| 5mg/kg q4w | Phase II: Progression Free Survival (PFS) Per irRC | 1.7 Percentage of participants |
Secondary
Phase I: Presence and/or Concentration of Anti-PDR001
Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment.
Time frame: 42 months
Population: Immunogenicity incidence Set: The Immunogenicity incidence set includes all subjects in FAS with a determinant baseline immunoglobulin (IG) sample and at least one determinant post-baseline IG sample.~Treatment-induced ADA-positive was performed on ADA-positive patients only. Treatment-boosted ADA-positive was performed on ADA-positive patients only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 4 Participants |
| 1mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 3 Participants |
| 1mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 5 Participants |
| 1mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 11 Participants |
| 1mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 10 Participants |
| 1mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 1 Participants |
| 3mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 8 Participants |
| 3mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 9 Participants |
| 3mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 1 Participants |
| 3mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 1 Participants |
| 3mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 2 Participants |
| 3mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 2 Participants |
| 10mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 2 Participants |
| 10mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 2 Participants |
| 10mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 2 Participants |
| 10mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 1 Participants |
| 10mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 0 Participants |
| 10mg/kg q2w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 1 Participants |
| 3mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 2 Participants |
| 3mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 21 Participants |
| 3mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 19 Participants |
| 3mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 8 Participants |
| 3mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 9 Participants |
| 3mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 6 Participants |
| 5mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 4 Participants |
| 5mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 1 Participants |
| 5mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 1 Participants |
| 5mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 5 Participants |
| 5mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 1 Participants |
| 5mg/kg q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 0 Participants |
| All Phase II Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 8 Participants |
| All Phase II Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 1 Participants |
| All Phase II Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 0 Participants |
| All Phase II Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 9 Participants |
| All Phase II Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 1 Participants |
| All Phase II Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 1 Participants |
| All Phase I q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 2 Participants |
| All Phase I q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 14 Participants |
| All Phase I q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 0 Participants |
| All Phase I q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 2 Participants |
| All Phase I q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 12 Participants |
| All Phase I q4w | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 2 Participants |
| All Phase I Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-boosted ADA-positive | 6 Participants |
| All Phase I Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-positive sample at baseline | 11 Participants |
| All Phase I Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-positive (i.e., ADA incidence) | 10 Participants |
| All Phase I Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | Patients with ADA-negative sample at baseline | 35 Participants |
| All Phase I Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | Treatment-induced ADA-positive | 4 Participants |
| All Phase I Patients | Phase I: Presence and/or Concentration of Anti-PDR001 | ADA-negative | 31 Participants |
Secondary
Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau)
AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Population: Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUCtau (n = 16, 13, 10, 6, 10) | 126 day*ug/mL | Geometric Coefficient of Variation 29.5 |
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUClast | 125 day*ug/mL | Geometric Coefficient of Variation 29.9 |
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUCtau (n = 8, 4, 4, 2, 2) | 270 day*ug/mL | Geometric Coefficient of Variation 52.5 |
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUClast | 260 day*ug/mL | Geometric Coefficient of Variation 44.8 |
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | Cycle (C) 1: AUC0-336h (n=16, 13, 10, 6, 10) | 126 day*ug/mL | Geometric Coefficient of Variation 29.5 |
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUCinf (n = 1, 0,0,2,3) | 123 day*ug/mL | Geometric Coefficient of Variation 0 |
| 3mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUCtau (n = 16, 13, 10, 6, 10) | 324 day*ug/mL | Geometric Coefficient of Variation 24.4 |
| 3mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | Cycle (C) 1: AUC0-336h (n=16, 13, 10, 6, 10) | 324 day*ug/mL | Geometric Coefficient of Variation 24.4 |
| 3mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUClast | 353 day*ug/mL | Geometric Coefficient of Variation 31.4 |
| 3mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUClast | 995 day*ug/mL | Geometric Coefficient of Variation 60.5 |
| 3mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUCtau (n = 8, 4, 4, 2, 2) | 1150 day*ug/mL | Geometric Coefficient of Variation 51.1 |
| 10mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | Cycle (C) 1: AUC0-336h (n=16, 13, 10, 6, 10) | 1270 day*ug/mL | Geometric Coefficient of Variation 20.3 |
| 10mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUCtau (n = 8, 4, 4, 2, 2) | 3110 day*ug/mL | Geometric Coefficient of Variation 33.1 |
| 10mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUCtau (n = 16, 13, 10, 6, 10) | 1270 day*ug/mL | Geometric Coefficient of Variation 20.3 |
| 10mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUClast | 2520 day*ug/mL | Geometric Coefficient of Variation 58.4 |
| 10mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUClast | 1240 day*ug/mL | Geometric Coefficient of Variation 21.6 |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUClast | 933 day*ug/mL | Geometric Coefficient of Variation 21.3 |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUCtau (n = 8, 4, 4, 2, 2) | 1040 day*ug/mL | Geometric Coefficient of Variation 19.1 |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUCinf (n = 1, 0,0,2,3) | 384 day*ug/mL | Geometric Coefficient of Variation 9.8 |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUCtau (n = 16, 13, 10, 6, 10) | 524 day*ug/mL | Geometric Coefficient of Variation 39.6 |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | Cycle (C) 1: AUC0-336h (n=16, 13, 10, 6, 10) | 350 day*ug/mL | Geometric Coefficient of Variation 35 |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUClast | 522 day*ug/mL | Geometric Coefficient of Variation 39.1 |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUClast | 2560 day*ug/mL | Geometric Coefficient of Variation 37.2 |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUCtau (n = 16, 13, 10, 6, 10) | 984 day*ug/mL | Geometric Coefficient of Variation 41.9 |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C3: AUCtau (n = 8, 4, 4, 2, 2) | 2770 day*ug/mL | Geometric Coefficient of Variation 26.6 |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUCinf (n = 1, 0,0,2,3) | 726 day*ug/mL | Geometric Coefficient of Variation 16 |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | Cycle (C) 1: AUC0-336h (n=16, 13, 10, 6, 10) | 638 day*ug/mL | Geometric Coefficient of Variation 35.3 |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) | C1: AUClast | 943 day*ug/mL | Geometric Coefficient of Variation 37.4 |
Secondary
Phase I: Serum Pharmacokinetic (PK) Parameter Cmax
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Population: Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 15, 15, 10, 6, 9) | 18.2 ug/mL | Geometric Coefficient of Variation 26.5 |
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 10, 7, 3, 3, 2) | 29.7 ug/mL | Geometric Coefficient of Variation 41 |
| 3mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 15, 15, 10, 6, 9) | 53.8 ug/mL | Geometric Coefficient of Variation 23.6 |
| 3mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 10, 7, 3, 3, 2) | 112 ug/mL | Geometric Coefficient of Variation 27.3 |
| 10mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 15, 15, 10, 6, 9) | 185 ug/mL | Geometric Coefficient of Variation 18.3 |
| 10mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 10, 7, 3, 3, 2) | 312 ug/mL | Geometric Coefficient of Variation 30 |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 10, 7, 3, 3, 2) | 69.7 ug/mL | Geometric Coefficient of Variation 9.4 |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 15, 15, 10, 6, 9) | 53.8 ug/mL | Geometric Coefficient of Variation 29.4 |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 15, 15, 10, 6, 9) | 106 ug/mL | Geometric Coefficient of Variation 34.2 |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 10, 7, 3, 3, 2) | 179 ug/mL | Geometric Coefficient of Variation 45.2 |
Secondary
Phase I: Serum Pharmacokinetic (PK) Parameter Tmax
The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Population: Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n = 15, 15, 10, 6, 9) | 1.58 hour |
| 1mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 10, 7, 3, 3, 2) | 1.55 hour |
| 3mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n = 15, 15, 10, 6, 9) | 1.57 hour |
| 3mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 10, 7, 3, 3, 2) | 1.55 hour |
| 10mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n = 15, 15, 10, 6, 9) | 1.55 hour |
| 10mg/kg q2w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 10, 7, 3, 3, 2) | 1.58 hour |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 10, 7, 3, 3, 2) | 1.5 hour |
| 3mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n = 15, 15, 10, 6, 9) | 1.55 hour |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n = 15, 15, 10, 6, 9) | 1.58 hour |
| 5mg/kg q4w | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 10, 7, 3, 3, 2) | 1.3 hour |
Secondary
Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment.
Time frame: 27 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg/kg q2w | Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 56.3 Percentage of participants |
| 3mg/kg q2w | Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 46.7 Percentage of participants |
| 10mg/kg q2w | Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 27.3 Percentage of participants |
| 3mg/kg q4w | Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 45.2 Percentage of participants |
| 5mg/kg q4w | Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 50.0 Percentage of participants |
| All Phase II Patients | Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 20.0 Percentage of participants |
| All Phase I q4w | Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 31.3 Percentage of participants |
| All Phase I Patients | Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 | 41.4 Percentage of participants |
Secondary
Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau)
AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)
Population: Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCtau (n= 54, 55, 32, 48, 36) | 1010 day*ug/mL | Geometric Coefficient of Variation 39.8 |
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCinf (n = 13, 8, 7, 5, 2) | 1090 day*ug/mL | Geometric Coefficient of Variation 29.6 |
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUC0-336h (n = 36, 49, 12, 40, 16) | 1210 day*ug/mL | Geometric Coefficient of Variation 36.3 |
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUC0-336h (n =58, 58, 37, 54, 37) | 681 day*ug/mL | Geometric Coefficient of Variation 39.4 |
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUCtau (n= 31, 44, 7, 38, 14) | 1940 day*ug/mL | Geometric Coefficient of Variation 35.5 |
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUClast (n = 37, 51, 16, 44, 19) | 1860 day*ug/mL | Geometric Coefficient of Variation 39.9 |
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUClast | 980 day*ug/mL | Geometric Coefficient of Variation 42.5 |
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUCinf (n = 1, 1, 1, 1, 0) | 1050 day*ug/mL | — |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUCinf (n = 1, 1, 1, 1, 0) | 1070 day*ug/mL | — |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUClast (n = 37, 51, 16, 44, 19) | 1650 day*ug/mL | Geometric Coefficient of Variation 59.7 |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUCtau (n= 31, 44, 7, 38, 14) | 1790 day*ug/mL | Geometric Coefficient of Variation 53.4 |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUC0-336h (n =58, 58, 37, 54, 37) | 775 day*ug/mL | Geometric Coefficient of Variation 31.7 |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCtau (n= 54, 55, 32, 48, 36) | 1190 day*ug/mL | Geometric Coefficient of Variation 35 |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUC0-336h (n = 36, 49, 12, 40, 16) | 1140 day*ug/mL | Geometric Coefficient of Variation 43.8 |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUClast | 1020 day*ug/mL | Geometric Coefficient of Variation 109.9 |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCinf (n = 13, 8, 7, 5, 2) | 1080 day*ug/mL | Geometric Coefficient of Variation 45.4 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUClast (n = 37, 51, 16, 44, 19) | 1630 day*ug/mL | Geometric Coefficient of Variation 73.4 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUCtau (n= 31, 44, 7, 38, 14) | 1920 day*ug/mL | Geometric Coefficient of Variation 44.4 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCinf (n = 13, 8, 7, 5, 2) | 1240 day*ug/mL | Geometric Coefficient of Variation 25.2 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUC0-336h (n =58, 58, 37, 54, 37) | 752 day*ug/mL | Geometric Coefficient of Variation 29.3 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUClast | 923 day*ug/mL | Geometric Coefficient of Variation 76.1 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCtau (n= 54, 55, 32, 48, 36) | 1130 day*ug/mL | Geometric Coefficient of Variation 34.9 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUC0-336h (n = 36, 49, 12, 40, 16) | 1360 day*ug/mL | Geometric Coefficient of Variation 45.7 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUCinf (n = 1, 1, 1, 1, 0) | 2340 day*ug/mL | — |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCtau (n= 54, 55, 32, 48, 36) | 689 day*ug/mL | Geometric Coefficient of Variation 40.4 |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUC0-336h (n =58, 58, 37, 54, 37) | 535 day*ug/mL | Geometric Coefficient of Variation 38.3 |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUClast | 602 day*ug/mL | Geometric Coefficient of Variation 62.2 |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUClast (n = 37, 51, 16, 44, 19) | 984 day*ug/mL | Geometric Coefficient of Variation 78 |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUCinf (n = 1, 1, 1, 1, 0) | 135 day*ug/mL | — |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCinf (n = 13, 8, 7, 5, 2) | 491 day*ug/mL | Geometric Coefficient of Variation 22.7 |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUCtau (n= 31, 44, 7, 38, 14) | 1100 day*ug/mL | Geometric Coefficient of Variation 54.5 |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUC0-336h (n = 36, 49, 12, 40, 16) | 850 day*ug/mL | Geometric Coefficient of Variation 50.6 |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUCtau (n= 31, 44, 7, 38, 14) | 2120 day*ug/mL | Geometric Coefficient of Variation 32.7 |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUC0-336h (n =58, 58, 37, 54, 37) | 704 day*ug/mL | Geometric Coefficient of Variation 28.2 |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCinf (n = 13, 8, 7, 5, 2) | 1160 day*ug/mL | Geometric Coefficient of Variation 7.1 |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUClast | 865 day*ug/mL | Geometric Coefficient of Variation 69.8 |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C1: AUCtau (n= 54, 55, 32, 48, 36) | 1070 day*ug/mL | Geometric Coefficient of Variation 31.3 |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUC0-336h (n = 36, 49, 12, 40, 16) | 1290 day*ug/mL | Geometric Coefficient of Variation 30 |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) | C3: AUClast (n = 37, 51, 16, 44, 19) | 1600 day*ug/mL | Geometric Coefficient of Variation 88 |
Secondary
Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Population: Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 52, 58, 32, 55, 35) | 103 ug/mL | Geometric Coefficient of Variation 37 |
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 33, 45, 11, 39, 18) | 151 ug/mL | Geometric Coefficient of Variation 32 |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 52, 58, 32, 55, 35) | 111 ug/mL | Geometric Coefficient of Variation 26.6 |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 33, 45, 11, 39, 18) | 141 ug/mL | Geometric Coefficient of Variation 33.4 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 52, 58, 32, 55, 35) | 114 ug/mL | Geometric Coefficient of Variation 23.6 |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 33, 45, 11, 39, 18) | 163 ug/mL | Geometric Coefficient of Variation 34.7 |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 33, 45, 11, 39, 18) | 103 ug/mL | Geometric Coefficient of Variation 36.6 |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 52, 58, 32, 55, 35) | 79.9 ug/mL | Geometric Coefficient of Variation 31.8 |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C1 (n = 52, 58, 32, 55, 35) | 100 ug/mL | Geometric Coefficient of Variation 27.3 |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax | C3 (n = 33, 45, 11, 39, 18) | 146 ug/mL | Geometric Coefficient of Variation 22.6 |
Secondary
Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax
The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
Time frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)
Population: Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n= 52, 58, 32, 55, 35) | 1.58 hour |
| 1mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 33, 45, 11, 39, 18) | 1.6 hour |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n= 52, 58, 32, 55, 35) | 1.58 hour |
| 3mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 33, 45, 11, 39, 18) | 1.55 hour |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n= 52, 58, 32, 55, 35) | 1.58 hour |
| 10mg/kg q2w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 33, 45, 11, 39, 18) | 1.53 hour |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 33, 45, 11, 39, 18) | 1.58 hour |
| 3mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n= 52, 58, 32, 55, 35) | 1.65 hour |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C1 (n= 52, 58, 32, 55, 35) | 1.55 hour |
| 5mg/kg q4w | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax | C3 (n = 33, 45, 11, 39, 18) | 1.57 hour |
Secondary
Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) \> 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug.
Time frame: 27 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg/kg q2w | Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC | 62.5 Percentage of participants |
| 3mg/kg q2w | Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC | 53.3 Percentage of participants |
| 10mg/kg q2w | Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC | 27.3 Percentage of participants |
| 3mg/kg q4w | Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC | 50.0 Percentage of participants |
| 5mg/kg q4w | Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC | 50.0 Percentage of participants |
| All Phase II Patients | Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC | 30.0 Percentage of participants |
| All Phase I q4w | Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC | 37.5 Percentage of participants |
| All Phase I Patients | Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC | 46.6 Percentage of participants |
Secondary
Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC)
ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug.
Time frame: 27 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg/kg q2w | Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) | 0.00 Percentage of participants |
| 3mg/kg q2w | Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) | 6.7 Percentage of participants |
| 10mg/kg q2w | Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) | 9.1 Percentage of participants |
| 3mg/kg q4w | Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) | 4.8 Percentage of participants |
| 5mg/kg q4w | Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) | 0.0 Percentage of participants |
| All Phase II Patients | Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) | 0.0 Percentage of participants |
| All Phase I q4w | Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) | 0.0 Percentage of participants |
| All Phase I Patients | Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) | 3.4 Percentage of participants |
Secondary
Phase l Only: Progression Free Survival (PFS) as Per irRC
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment, where the compound being evaluated is an immuno-oncology drug.
Time frame: 27 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1mg/kg q2w | Phase l Only: Progression Free Survival (PFS) as Per irRC | 3.6 Percentage of participants |
| 3mg/kg q2w | Phase l Only: Progression Free Survival (PFS) as Per irRC | 2.7 Percentage of participants |
| 10mg/kg q2w | Phase l Only: Progression Free Survival (PFS) as Per irRC | 2.2 Percentage of participants |
| 3mg/kg q4w | Phase l Only: Progression Free Survival (PFS) as Per irRC | 2.7 Percentage of participants |
| 5mg/kg q4w | Phase l Only: Progression Free Survival (PFS) as Per irRC | 1.8 Percentage of participants |
Secondary
Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1
ORR is the percentage of participants with a best overall response of complete response CR or partial response PR as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment.
Time frame: 27 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1mg/kg q2w | Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 | 0.00 Percentage of participants |
| 3mg/kg q2w | Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 | 6.7 Percentage of participants |
| 10mg/kg q2w | Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 | 9.1 Percentage of participants |
| 3mg/kg q4w | Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 | 4.8 Percentage of participants |
| 5mg/kg q4w | Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 | 0.0 Percentage of participants |
| All Phase II Patients | Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 | 0.0 Percentage of participants |
| All Phase I q4w | Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 | 0.0 Percentage of participants |
| All Phase I Patients | Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 | 3.4 Percentage of participants |
Secondary
Phase l: Progression Free Survival (PFS) as Per RECIST v1.1
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. RECIST criteria is a set of published rules that define when tumors in cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment.
Time frame: 27 months
Population: Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1mg/kg q2w | Phase l: Progression Free Survival (PFS) as Per RECIST v1.1 | 3.5 Percentage of participants |
| 3mg/kg q2w | Phase l: Progression Free Survival (PFS) as Per RECIST v1.1 | 1.9 Percentage of participants |
| 10mg/kg q2w | Phase l: Progression Free Survival (PFS) as Per RECIST v1.1 | 2.2 Percentage of participants |
| 3mg/kg q4w | Phase l: Progression Free Survival (PFS) as Per RECIST v1.1 | 2.7 Percentage of participants |
| 5mg/kg q4w | Phase l: Progression Free Survival (PFS) as Per RECIST v1.1 | 1.8 Percentage of participants |
Post Hoc
All Collected Deaths
On treatment deaths were collected from the start of study treatment up to 30 days after last study treatment exposure, for a maximum duration of 114.3 weeks for Phase I part (treatment duration ranged from 2 to 110.3 weeks) and a maximum duration of 194.9 weeks for Phase II part (treatment duration ranged from 0.6 tp 190.9 weeks). Total deaths were collected from the start of treatment up to end of follow-up phase (approx. 70 months).
Time frame: On treatment deaths: approx. 114.3 weeks (Phase I) & 194.9 weeks (phase II), all deaths: approx. 70 months
Population: Clinical database population: All treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1mg/kg q2w | All Collected Deaths | Total deaths | 10 Participants |
| 1mg/kg q2w | All Collected Deaths | On-treatment deaths | 2 Participants |
| 3mg/kg q2w | All Collected Deaths | On-treatment deaths | 2 Participants |
| 3mg/kg q2w | All Collected Deaths | Total deaths | 10 Participants |
| 10mg/kg q2w | All Collected Deaths | Total deaths | 6 Participants |
| 10mg/kg q2w | All Collected Deaths | On-treatment deaths | 1 Participants |
| 3mg/kg q4w | All Collected Deaths | On-treatment deaths | 1 Participants |
| 3mg/kg q4w | All Collected Deaths | Total deaths | 4 Participants |
| 5mg/kg q4w | All Collected Deaths | On-treatment deaths | 2 Participants |
| 5mg/kg q4w | All Collected Deaths | Total deaths | 7 Participants |
| All Phase II Patients | All Collected Deaths | On-treatment deaths | 4 Participants |
| All Phase II Patients | All Collected Deaths | Total deaths | 39 Participants |
| All Phase I q4w | All Collected Deaths | On-treatment deaths | 4 Participants |
| All Phase I q4w | All Collected Deaths | Total deaths | 32 Participants |
| All Phase I Patients | All Collected Deaths | Total deaths | 28 Participants |
| All Phase I Patients | All Collected Deaths | On-treatment deaths | 4 Participants |
| NSCLC 300 mg/q3w | All Collected Deaths | On-treatment deaths | 12 Participants |
| NSCLC 300 mg/q3w | All Collected Deaths | Total deaths | 47 Participants |
| ATC 400 mg/q4w | All Collected Deaths | Total deaths | 31 Participants |
| ATC 400 mg/q4w | All Collected Deaths | On-treatment deaths | 11 Participants |