Advanced Solid Tumors
Conditions
Keywords
Programmed Cell Death Protein 1 (PD-1, PD1),, Programmed Cell Death Ligand 1 (PD-L1, PDL1), Programmed Cell Death Ligand 2 (PD-L2, PDL2)
Brief summary
This study will assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of quavonlimab when used in combination with pembrolizumab in participants with advanced solid tumors.
Detailed description
After screening, participants will be assigned to the Dose Escalation, Dose Confirmation, Efficacy Expansion, or Coformulation Phase. The Dose Escalation Phase will evaluate available PK and safety data including dose limiting toxicities (DLTs). The Dose Confirmation Phase will gather additional safety, tolerability, PK, and preliminary efficacy data of quavonlimab in combination with pembrolizumab, and will include first-line advanced/metastatic non-small cell lung cancer (NSCLC) and second line (and beyond) advanced/metastatic small cell lung cancer (SCLC). The purpose of the Efficacy Expansion Phase is to gather preliminary anti-tumor efficacy data for quavonlimab in combination with pembrolizumab as well as for quavonlimab monotherapy in the specific target population of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma. The Coformulation Phase will evaluate the safety and PK of a coformulated product of pembrolizumab/quavonlimab (MK-1308A) in comparison to that of the single, co-administered products given at the same dose and schedule, and include participants with advanced solid tumors and participants from mainland China.
Interventions
BIOLOGICALQuavonlimab
Quavonlimab is administered intravenously (IV) during the Dose Escalation Phase and Dose Confirmation Phase at either DL1 or DL2, and is administered IV during the Efficacy Expansion Phase at DL2.
BIOLOGICALPembrolizumab
Pembrolizumab is administered IV at PDL1 on Day 1 of each cycle starting Cycle 2 for the Dose Escalation Phase or starting Cycle 1 of the Dose Confirmation Phase. Pembrolizumab is administered IV at PDL2 on Day 1 of each cycle for the Efficacy Expansion Phase (Arm G).
Pembrolizumab/Quavonlimab is a coformulated product composed of quavonlimab at DL1 in combination with pembrolizumab at dose level 2 (PDL2).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For Dose Escalation Phase: * Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor (except NSCLC for Cohorts 2 and 3) by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit For Dose Confirmation Phase NSCLC Arms (A, B, C, and E): * Have newly diagnosed histologically or cytologically-confirmed stage IIIB/stage IV NSCLC. Epidermal growth factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK) translocation-directed therapy is not indicated as primary therapy. Participant must not have received prior systemic treatment for advanced NSCLC or must have received previous neoadjuvant and adjuvant chemotherapies ≥6 months before dosing of study drug if prior systemic treatment was given for early stage disease For Dose Confirmation Phase SCLC Arm (Arm D): * Have histologically- or cytologically-confirmed metastatic (Stage III/IV) SCLC with progressive disease after ≥1 platinum-based chemotherapy regimen. Participants with platinum-sensitive disease are eligible * Have measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology * Have Eastern Cooperative Oncology Group (ECOG) Performance Scale status of 0 or 1 * A female participant is eligible to participate if she is not pregnant or breastfeeding and at least 1 of the following conditions applies: * Is not a woman of child bearing potential (WOCBP) OR * Is a WOCBP and using a contraceptive method that is highly effective during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, whichever comes last * Female participants of childbearing potential must have negative urine or serum pregnancy test within 24 hours for urine and within 72 hours for serum prior to receiving the first dose of study treatment * Male participants with a female partner(s) of child-bearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication and refrain from donating sperm during this period * Must submit an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample) For Efficacy Expansion Phase Arms F and G: * Have histologically/cytologically-confirmed unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8, not amenable to local therapy * Have at least 1 measurable lesion by CT or MRI per RECIST 1.1 by BICR. Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions * Participants with unresectable Stage III or IV disease must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies (combinations with anti-cytotoxic T-lymphocyte associated protein 4 \[CTLA-4\] agents will not be allowed) * Participants who receive anti-PD-1 therapy as adjuvant treatment following complete resection of Stage III or IV melanoma and have disease recurrence (unresectable loco-regional disease or distant metastases) while on active treatment or within 6 months of stopping anti-PD-1 are eligible * Have submitted pre-trial imaging and provided a baseline tumor sample * Proto-oncogene B-raf (BRAF) V600 mutation-positive melanoma participants should have received targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however, they are not required to progress on this treatment prior to enrollment * BRAF V600E mutation-positive melanoma participants who have NOT received a BRAF inhibitor (either as adjuvant therapy or in the metastatic disease setting) with lactate dehydrogenase (LDH) \< local upper limit of normal (ULN), no clinically significant tumor-related symptoms, and absence of rapidly progressing metastatic melanoma. Approximately 10 participants each from Arms F and G will have 2 mandatory biopsies For Dose Coformulation Phase Arm I: * Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for or refused all treatment known to confer clinical benefit * Meet all requirements for Dose Escalation Phase and Dose Confirmation Phase For the Coformulation Phase - Arm K (China only): * Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit * Be a Chinese participant residing in China.
Exclusion criteria
* For all phases of the study: Has received previous treatment with another agent targeting cytotoxic T lymphocyte leukocyte antigen (CTLA)-4 For Dose Confirmation Phase: * Has received previous treatment with another agent targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor * Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier * Has received lung radiation therapy of \>30 Gray (Gy) within 6 months before the first dose of study treatment * Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of quavonlimab. * Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years For Dose Escalation Cohorts (1-3) and Dose Confirmation Arms (A-E): * Has known untreated central nervous system (CNS) metastases. Has known carcinomatous meningitis * Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse events (irAE) * Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study drug * Has any active infection requiring therapy * Has a history of interstitial lung disease, history of noninfectious pneumonitis that required steroids (or has current pneumonitis), or history of inflammatory bowel disease * Has an active autoimmune disease that has required systemic treatment in the past 2 years * Has clinically significant cardiac disease * Has received a live or live attenuated vaccine within 28 days of planned treatment start * Has known history of human immunodeficiency virus (HIV) and/or known active Hepatitis B or C infections, and/or known to be positive for hepatitis B surface antigen (HBsAg)/ hepatitis B virus (HBV) DNA * Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the trial * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with screening and for up to 120 days following cessation of pembrolizumab or pembrolizumab/quavonlimab * Has not fully recovered from any effects of major surgery without significant detectable infection For Arm F and G (Efficacy Expansion Phase) and Arm K (Coformulation Phase) ONLY: * Has known active CNS metastases and/or carcinomatous meningitis * Has not had resolution of anti-PD-1 antibody-related AEs, including immune-mediated AEs back to Grade ≤1 or baseline (not applicable to Arm K) * Has not discontinued steroid treatment for an irAE for at least 2 weeks prior to the first dose of study drug (not applicable to Arm K) * Has ocular melanoma (not applicable to Arm K) * Has mucosal melanoma (not applicable to Arm K) * Has had an allogenic tissue/solid organ transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) | Up to 6 weeks | DLT was defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥ Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for \>1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 of Dose Escalation or Cycle 2 of Dose Confirmation due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity. |
| Number of Participants With ≥1 Adverse Event (AE) | Up to approximately 77 months | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who experienced an AE are presented. |
| Number of Participants Discontinuing Study Treatment Due to an AE | Up to approximately 26 months | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who discontinued study treatment due to an AE are presented. |
| Efficacy Expansion: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Based on Adjusted Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Up to approximately 72 months | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per adjusted Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR in the concurrent randomized subset as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) of Quavonlimab | At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days. | Cmax was defined as the maximum concentration of quavonlimab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. Cmax of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days. |
| Minimum Concentration (Cmin) of Quavonlimab | At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days. | Cmin was defined as the minimum or trough concentration of quavonlimab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. Cmin of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days. |
| Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Cohorts 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycles 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days. | Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with pembrolizumab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for arm G and cross over phase. |
| Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days. | AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. AUC of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days. |
| Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | Up to approximately 72 months | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, no analysis was planned for the cross over phase. |
| Efficacy Expansion: Duration of Response (DOR) as Assessed by BICR Based on Adjusted RECIST v1.1 | Up to approximately 72 months | DOR was defined as the time from first documented evidence of complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint. |
| Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Cohort 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycle 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, G, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days. | Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with quavonlimab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted (TB)). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. |
| Maximum Concentration (Cmax) of Pembrolizumab | At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days. | Cmax was defined as the maximum concentration of pembrolizumab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. Cmax of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days. |
| Minimum Concentration (Cmin) of Pembrolizumab | At designated time points up to - Cohorts 1-3: Day 1 Cycle 4, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days. | Cmin was defined as the minimum or trough concentration of pembrolizumab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. Cmin of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3, Day 1 on Cycle 4. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days. |
| Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days. | AUC was defined as a measure of quavonlimab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. AUC of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days. |
Countries
Australia, Canada, Chile, China, France, Greece, Israel, Italy, Japan, New Zealand, Poland, South Africa, South Korea, Spain, Sweden, United States
Participant flow
Pre-assignment details
Per protocol, twenty-one participants who progressed by radiographic evaluation on monotherapy with MK-1308 (Arm G) after consultation with the sponsor crossed over to the combination treatment arm (MK-1308 25 mg + Pembrolizumab 400 mg)
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months). | 14 |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months). | 18 |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 200 mg quavonlimab monotherapy followed by 200 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months). | 8 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months). | 40 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 25 mg quavonlimab every 6 weeks (Q6W). Participants were treated for up to 35 cycles total (up to approximately 24 months). | 40 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months). | 41 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic small cell lung cancer (SCLC) received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months). | 40 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months). | 14 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma received 25 mg quavonlimab in combination with 400 mg pembrolizumab. Both quavonlimab and pembrolizumab were administered Q6W for 24 months. | 111 |
| Arm G: MK-1308 25 mg Q6W On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma received 25 mg quavonlimab Q6W for up to 24 months. | 40 |
| Arm I: MK-1308A Q6W (Co-form) On cycle 1, day 1 of the coformulation (Co-form) phase and during all subsequent cycles, participants with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months. | 29 |
| Arm K: MK-1308A Q6W (Co-form) On cycle 1, day 1 of the coformulation phase and during all subsequent cycles, participants in mainland China with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months. | 20 |
| Total | 415 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 12 | 17 | 7 | 32 | 29 | 30 | 33 | 9 | 84 | 33 | 22 | 15 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Randomized by Mistake without Study Treatment | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 0 | 1 | 3 | 9 | 7 | 2 | 4 | 23 | 6 | 7 | 5 |
| Overall Study | Withdrawal by Parent/Guardian | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 4 | 2 | 2 | 5 | 0 | 3 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Arm G: MK-1308 25 mg Q6W | Arm I: MK-1308A Q6W (Co-form) | Arm K: MK-1308A Q6W (Co-form) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 207 Participants | 6 Participants | 6 Participants | 17 Participants | 6 Participants | 22 Participants | 24 Participants | 23 Participants | 10 Participants | 58 Participants | 16 Participants | 13 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 208 Participants | 12 Participants | 2 Participants | 23 Participants | 8 Participants | 18 Participants | 17 Participants | 17 Participants | 4 Participants | 53 Participants | 24 Participants | 16 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 391 Participants | 17 Participants | 7 Participants | 40 Participants | 13 Participants | 37 Participants | 41 Participants | 39 Participants | 13 Participants | 102 Participants | 33 Participants | 29 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 8 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 132 Participants | 0 Participants | 0 Participants | 30 Participants | 0 Participants | 26 Participants | 26 Participants | 16 Participants | 8 Participants | 3 Participants | 0 Participants | 3 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 272 Participants | 17 Participants | 8 Participants | 10 Participants | 14 Participants | 14 Participants | 14 Participants | 23 Participants | 6 Participants | 105 Participants | 38 Participants | 23 Participants | 0 Participants |
| Sex: Female, Male Female | 158 Participants | 10 Participants | 4 Participants | 10 Participants | 11 Participants | 12 Participants | 17 Participants | 16 Participants | 5 Participants | 34 Participants | 18 Participants | 13 Participants | 8 Participants |
| Sex: Female, Male Male | 257 Participants | 8 Participants | 4 Participants | 30 Participants | 3 Participants | 28 Participants | 24 Participants | 24 Participants | 9 Participants | 77 Participants | 22 Participants | 16 Participants | 12 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 13 / 14 | 18 / 18 | 7 / 8 | 33 / 40 | 31 / 40 | 32 / 41 | 35 / 40 | 9 / 14 | 86 / 111 | 17 / 21 | 16 / 40 | 22 / 29 | 15 / 20 |
| other Total, other adverse events | 14 / 14 | 16 / 17 | 8 / 8 | 38 / 40 | 38 / 40 | 38 / 40 | 37 / 40 | 13 / 14 | 102 / 111 | 17 / 21 | 31 / 40 | 26 / 29 | 16 / 20 |
| serious Total, serious adverse events | 2 / 14 | 10 / 17 | 4 / 8 | 20 / 40 | 14 / 40 | 23 / 40 | 16 / 40 | 10 / 14 | 31 / 111 | 4 / 21 | 9 / 40 | 15 / 29 | 4 / 20 |
Outcome results
Primary
Efficacy Expansion: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Based on Adjusted Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per adjusted Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR in the concurrent randomized subset as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint.
Time frame: Up to approximately 72 months
Population: All participants with a baseline scan that demonstrated measurable disease and who were administered at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Efficacy Expansion: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Based on Adjusted Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 4.9 Percentage of participants |
| Arm G: MK-1308 25 mg Q6W | Efficacy Expansion: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Based on Adjusted Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 2.5 Percentage of participants |
95% CI: [-8.7, 14.1]Percent Difference
Primary
Number of Participants Discontinuing Study Treatment Due to an AE
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who discontinued study treatment due to an AE are presented.
Time frame: Up to approximately 26 months
Population: All participants who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants Discontinuing Study Treatment Due to an AE | 1 Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants Discontinuing Study Treatment Due to an AE | 4 Participants |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Number of Participants Discontinuing Study Treatment Due to an AE | 3 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants Discontinuing Study Treatment Due to an AE | 7 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants Discontinuing Study Treatment Due to an AE | 7 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants Discontinuing Study Treatment Due to an AE | 17 Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants Discontinuing Study Treatment Due to an AE | 7 Participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants Discontinuing Study Treatment Due to an AE | 6 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants Discontinuing Study Treatment Due to an AE | 14 Participants |
| Arm G: MK-1308 25 mg Q6W | Number of Participants Discontinuing Study Treatment Due to an AE | 1 Participants |
| Arm I: MK-1308A Q6W (Co-form) | Number of Participants Discontinuing Study Treatment Due to an AE | 4 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants Discontinuing Study Treatment Due to an AE | 2 Participants |
Primary
Number of Participants With ≥1 Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who experienced an AE are presented.
Time frame: Up to approximately 77 months
Population: All participants who received at least one dose of study intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With ≥1 Adverse Event (AE) | 14 Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With ≥1 Adverse Event (AE) | 17 Participants |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With ≥1 Adverse Event (AE) | 8 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With ≥1 Adverse Event (AE) | 39 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With ≥1 Adverse Event (AE) | 38 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With ≥1 Adverse Event (AE) | 40 Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With ≥1 Adverse Event (AE) | 38 Participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With ≥1 Adverse Event (AE) | 14 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With ≥1 Adverse Event (AE) | 104 Participants |
| Arm G: MK-1308 25 mg Q6W | Number of Participants With ≥1 Adverse Event (AE) | 37 Participants |
| Arm I: MK-1308A Q6W (Co-form) | Number of Participants With ≥1 Adverse Event (AE) | 28 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With ≥1 Adverse Event (AE) | 18 Participants |
Primary
Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT)
DLT was defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥ Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for \>1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 of Dose Escalation or Cycle 2 of Dose Confirmation due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity.
Time frame: Up to 6 weeks
Population: The DLT evaluable population consists of all participants who received ≥1 dose of study treatment who finished the DLT observation period in the dose escalation or dose confirmation phase. Per protocol, no analysis was planned for the efficacy expansion phase (Arms F and G), coformulation phase (Arms I and K) and cross over phase (MK-1308 25 mg and Pembrolizumab 400 mg).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) | 13.3 Percentage of Participants |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) | 7.5 Percentage of Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) | 5.0 Percentage of Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) | 10.0 Percentage of Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) | 10.0 Percentage of Participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT) | 7.1 Percentage of Participants |
Secondary
Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab
AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. AUC of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Population: Participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 729 day*μg/mL | Geometric Coefficient of Variation 18.3 |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 546 day*μg/mL | Geometric Coefficient of Variation 40.5 |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 727 day*μg/mL | Geometric Coefficient of Variation 24.5 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 3 | 911 day*μg/mL | Geometric Coefficient of Variation 22.7 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 1 | 608 day*μg/mL | Geometric Coefficient of Variation 24.6 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 788 day*μg/mL | Geometric Coefficient of Variation 24.7 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 854 day*μg/mL | Geometric Coefficient of Variation 19.9 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 3 | 971 day*μg/mL | Geometric Coefficient of Variation 22.9 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 1 | 620 day*μg/mL | Geometric Coefficient of Variation 25.9 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 822 day*μg/mL | Geometric Coefficient of Variation 25 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 1 | 627 day*μg/mL | Geometric Coefficient of Variation 20.6 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 3 | 944 day*μg/mL | Geometric Coefficient of Variation 26 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 3 | 1050 day*μg/mL | Geometric Coefficient of Variation 20.8 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 1 | 642 day*μg/mL | Geometric Coefficient of Variation 23.9 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 877 day*μg/mL | Geometric Coefficient of Variation 28.3 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 3 | 872 day*μg/mL | Geometric Coefficient of Variation 16.3 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 794 day*μg/mL | Geometric Coefficient of Variation 18 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 1 | 554 day*μg/mL | Geometric Coefficient of Variation 15.6 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 3 | 2410 day*μg/mL | Geometric Coefficient of Variation 29.5 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 2370 day*μg/mL | Geometric Coefficient of Variation 40.6 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 1 | 2050 day*μg/mL | Geometric Coefficient of Variation 33.6 |
| Arm I: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 1 | 2250 day*μg/mL | Geometric Coefficient of Variation 18.7 |
| Arm I: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 2820 day*μg/mL | Geometric Coefficient of Variation 29.7 |
| Arm I: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 3 | 3410 day*μg/mL | Geometric Coefficient of Variation 16.1 |
| Arm K: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 2 | 1770 day*μg/mL | Geometric Coefficient of Variation 34.4 |
| Arm K: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 1 | 1610 day*μg/mL | Geometric Coefficient of Variation 25 |
| Arm K: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab | Cycle 3 | 2440 day*μg/mL | Geometric Coefficient of Variation 39.8 |
Secondary
Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308)
AUC was defined as a measure of quavonlimab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. AUC of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Population: Participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 2 | 91.5 day*μg/mL | Geometric Coefficient of Variation 19.9 |
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 68.2 day*μg/mL | Geometric Coefficient of Variation 17.7 |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 2 | 178 day*μg/mL | Geometric Coefficient of Variation 53.9 |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 160 day*μg/mL | Geometric Coefficient of Variation 19.5 |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 510 day*μg/mL | Geometric Coefficient of Variation 25.7 |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 2 | 751 day*μg/mL | Geometric Coefficient of Variation 23.4 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 2 | 73.6 day*μg/mL | Geometric Coefficient of Variation 26.4 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 55.0 day*μg/mL | Geometric Coefficient of Variation 26.6 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 3 | 64.3 day*μg/mL | Geometric Coefficient of Variation 56.5 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 69.6 day*μg/mL | Geometric Coefficient of Variation 33.5 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 3 | 59.4 day*μg/mL | Geometric Coefficient of Variation 74.9 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 3 | 182 day*μg/mL | Geometric Coefficient of Variation 75.1 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 199 day*μg/mL | Geometric Coefficient of Variation 36.2 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 222 day*μg/mL | Geometric Coefficient of Variation 39.7 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 3 | 193 day*μg/mL | Geometric Coefficient of Variation 90.8 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 178 day*μg/mL | Geometric Coefficient of Variation 17.6 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 2 | 192 day*μg/mL | Geometric Coefficient of Variation 17.7 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 3 | 186 day*μg/mL | Geometric Coefficient of Variation 22.1 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 77.1 day*μg/mL | Geometric Coefficient of Variation 32.7 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 3 | 95.2 day*μg/mL | Geometric Coefficient of Variation 63.4 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 2 | 94.4 day*μg/mL | Geometric Coefficient of Variation 43.9 |
| Arm G: MK-1308 25 mg Q6W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 92.8 day*μg/mL | Geometric Coefficient of Variation 38.1 |
| Arm G: MK-1308 25 mg Q6W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 2 | 65.9 day*μg/mL | Geometric Coefficient of Variation 27.8 |
| Arm G: MK-1308 25 mg Q6W | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 3 | 95.0 day*μg/mL | Geometric Coefficient of Variation 58.2 |
| Arm I: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 2 | 96.1 day*μg/mL | Geometric Coefficient of Variation 39.7 |
| Arm I: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 106 day*μg/mL | Geometric Coefficient of Variation 34.7 |
| Arm I: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 3 | 72.1 day*μg/mL | Geometric Coefficient of Variation 9.92 |
| Arm K: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 2 | 86.0 day*μg/mL | Geometric Coefficient of Variation 47.7 |
| Arm K: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 1 | 85.8 day*μg/mL | Geometric Coefficient of Variation 24.2 |
| Arm K: MK-1308A Q6W (Co-form) | Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308) | Cycle 3 | 92.3 day*μg/mL | Geometric Coefficient of Variation 60.2 |
Secondary
Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, no analysis was planned for the cross over phase.
Time frame: Up to approximately 72 months
Population: All participants with a baseline scan that demonstrated measurable disease and who were administered at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 0.0 Percentage of participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 0.0 Percentage of participants |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 25.0 Percentage of participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 32.5 Percentage of participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 37.5 Percentage of participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 30.0 Percentage of participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 15.0 Percentage of participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 35.7 Percentage of participants |
| Arm I: MK-1308A Q6W (Co-form) | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 10.3 Percentage of participants |
| Arm K: MK-1308A Q6W (Co-form) | Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1 | 20.0 Percentage of participants |
Secondary
Efficacy Expansion: Duration of Response (DOR) as Assessed by BICR Based on Adjusted RECIST v1.1
DOR was defined as the time from first documented evidence of complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint.
Time frame: Up to approximately 72 months
Population: Participants who received at least one dose of study intervention who had either a CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Efficacy Expansion: Duration of Response (DOR) as Assessed by BICR Based on Adjusted RECIST v1.1 | NA Months |
| Arm G: MK-1308 25 mg Q6W | Efficacy Expansion: Duration of Response (DOR) as Assessed by BICR Based on Adjusted RECIST v1.1 | 8.6 Months |
Secondary
Maximum Concentration (Cmax) of Pembrolizumab
Cmax was defined as the maximum concentration of pembrolizumab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. Cmax of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Population: Participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 79.8 μg/mL | Geometric Coefficient of Variation 31.3 |
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 93.9 μg/mL | Geometric Coefficient of Variation 21 |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 74.9 μg/mL | Geometric Coefficient of Variation 28.1 |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 82.3 μg/mL | Geometric Coefficient of Variation 32.3 |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 88.6 μg/mL | Geometric Coefficient of Variation 12.2 |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 78.7 μg/mL | Geometric Coefficient of Variation 32.4 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 1 | 71.8 μg/mL | Geometric Coefficient of Variation 24 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 84.2 μg/mL | Geometric Coefficient of Variation 16.9 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 82.9 μg/mL | Geometric Coefficient of Variation 20.2 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 1 | 77.1 μg/mL | Geometric Coefficient of Variation 26.7 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 92.3 μg/mL | Geometric Coefficient of Variation 27.5 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 88.2 μg/mL | Geometric Coefficient of Variation 20.9 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 83.9 μg/mL | Geometric Coefficient of Variation 23.2 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 91.8 μg/mL | Geometric Coefficient of Variation 21.7 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 1 | 74.0 μg/mL | Geometric Coefficient of Variation 27.8 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 1 | 73.6 μg/mL | Geometric Coefficient of Variation 22.3 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 90.4 μg/mL | Geometric Coefficient of Variation 23.7 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 98.0 μg/mL | Geometric Coefficient of Variation 27.4 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 84.8 μg/mL | Geometric Coefficient of Variation 18.6 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 1 | 70.9 μg/mL | Geometric Coefficient of Variation 35.3 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 84.5 μg/mL | Geometric Coefficient of Variation 13.8 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 150 μg/mL | Geometric Coefficient of Variation 28.9 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 1 | 149 μg/mL | Geometric Coefficient of Variation 29.1 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 153 μg/mL | Geometric Coefficient of Variation 22.1 |
| Arm I: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 164 μg/mL | Geometric Coefficient of Variation 22.8 |
| Arm I: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 1 | 149 μg/mL | Geometric Coefficient of Variation 23.8 |
| Arm I: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 168 μg/mL | Geometric Coefficient of Variation 22.3 |
| Arm K: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 1 | 128 μg/mL | Geometric Coefficient of Variation 21.9 |
| Arm K: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 2 | 139 μg/mL | Geometric Coefficient of Variation 20.5 |
| Arm K: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Pembrolizumab | Cycle 3 | 138 μg/mL | Geometric Coefficient of Variation 31.1 |
Secondary
Maximum Concentration (Cmax) of Quavonlimab
Cmax was defined as the maximum concentration of quavonlimab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. Cmax of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Population: Participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 2 | 9.41 μg/mL | Geometric Coefficient of Variation 20.4 |
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 9.11 μg/mL | Geometric Coefficient of Variation 24.7 |
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 8.23 μg/mL | Geometric Coefficient of Variation 26.1 |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 22.5 μg/mL | Geometric Coefficient of Variation 29.8 |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 23.3 μg/mL | Geometric Coefficient of Variation 48 |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 2 | 23.5 μg/mL | Geometric Coefficient of Variation 25.1 |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 88.3 μg/mL | Geometric Coefficient of Variation 16 |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 68.3 μg/mL | Geometric Coefficient of Variation 17.2 |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 2 | 71.9 μg/mL | Geometric Coefficient of Variation 29 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 7.28 μg/mL | Geometric Coefficient of Variation 30.6 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 2 | 8.58 μg/mL | Geometric Coefficient of Variation 22.4 |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 7.72 μg/mL | Geometric Coefficient of Variation 27.7 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 8.02 μg/mL | Geometric Coefficient of Variation 29.5 |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 6.98 μg/mL | Geometric Coefficient of Variation 43.7 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 22.7 μg/mL | Geometric Coefficient of Variation 33.1 |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 23.4 μg/mL | Geometric Coefficient of Variation 24.3 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 24.1 μg/mL | Geometric Coefficient of Variation 30.1 |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 24.2 μg/mL | Geometric Coefficient of Variation 50.4 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 2 | 26.3 μg/mL | Geometric Coefficient of Variation 24.7 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 25.0 μg/mL | Geometric Coefficient of Variation 20.6 |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 27.2 μg/mL | Geometric Coefficient of Variation 10.2 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 7.25 μg/mL | Geometric Coefficient of Variation 26.4 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 7.94 μg/mL | Geometric Coefficient of Variation 29.6 |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Maximum Concentration (Cmax) of Quavonlimab | Cycle 2 | 7.65 μg/mL | Geometric Coefficient of Variation 25.3 |
| Arm G: MK-1308 25 mg Q6W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 6.65 μg/mL | Geometric Coefficient of Variation 32.7 |
| Arm G: MK-1308 25 mg Q6W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 2 | 7.22 μg/mL | Geometric Coefficient of Variation 29.3 |
| Arm G: MK-1308 25 mg Q6W | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 7.42 μg/mL | Geometric Coefficient of Variation 30.4 |
| Arm I: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Quavonlimab | Cycle 2 | 8.17 μg/mL | Geometric Coefficient of Variation 26.2 |
| Arm I: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 8.06 μg/mL | Geometric Coefficient of Variation 26.5 |
| Arm I: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 7.25 μg/mL | Geometric Coefficient of Variation 21.9 |
| Arm K: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Quavonlimab | Cycle 1 | 8.23 μg/mL | Geometric Coefficient of Variation 26.7 |
| Arm K: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Quavonlimab | Cycle 2 | 7.99 μg/mL | Geometric Coefficient of Variation 29.7 |
| Arm K: MK-1308A Q6W (Co-form) | Maximum Concentration (Cmax) of Quavonlimab | Cycle 3 | 7.94 μg/mL | Geometric Coefficient of Variation 35.4 |
Secondary
Minimum Concentration (Cmin) of Pembrolizumab
Cmin was defined as the minimum or trough concentration of pembrolizumab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. Cmin of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3, Day 1 on Cycle 4. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Time frame: At designated time points up to - Cohorts 1-3: Day 1 Cycle 4, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Population: Participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 18.3 μg/mL |
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 4 | 34.3 μg/mL |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 4 | 14.1 μg/mL |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 11.3 μg/mL |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 4 | 23.5 μg/mL |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 19.0 μg/mL |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 1 | 13.3 μg/mL |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 19.6 μg/mL |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 3 | 25.7 μg/mL |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 24.3 μg/mL |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 3 | 27.5 μg/mL |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 1 | 13.1 μg/mL |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 3 | 25.5 μg/mL |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 1 | 14.3 μg/mL |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 20.4 μg/mL |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 1 | 15.6 μg/mL |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 25.2 μg/mL |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 3 | 29.3 μg/mL |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 18.9 μg/mL |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 1 | 11.5 μg/mL |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 3 | 27.7 μg/mL |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 1 | 21.9 μg/mL |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 23.1 μg/mL |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 3 | 24.5 μg/mL |
| Arm I: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 1 | 19.5 μg/mL |
| Arm I: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 3 | 34.0 μg/mL |
| Arm I: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 30.0 μg/mL |
| Arm K: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 3 | 26.6 μg/mL |
| Arm K: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 1 | 14.4 μg/mL |
| Arm K: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Pembrolizumab | Cycle 2 | 22.5 μg/mL |
Secondary
Minimum Concentration (Cmin) of Quavonlimab
Cmin was defined as the minimum or trough concentration of quavonlimab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. Cmin of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.
Time frame: At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.
Population: Participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 1.44 μg/mL |
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 1.75 μg/mL |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 1.91 μg/mL |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 3.29 μg/mL |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 2.83 μg/mL |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 17.4 μg/mL |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 8.01 μg/mL |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 1.17 μg/mL |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 1.42 μg/mL |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 1.05 μg/mL |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 0.00 μg/mL |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 0.00 μg/mL |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 0.00 μg/mL |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 0.00 μg/mL |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 25.2 μg/mL |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 15.6 μg/mL |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 29.3 μg/mL |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 3.20 μg/mL |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 3.40 μg/mL |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 2.91 μg/mL |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 0.00 μg/mL |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 0.00 μg/mL |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 0.00 μg/mL |
| Arm G: MK-1308 25 mg Q6W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 0.00 μg/mL |
| Arm G: MK-1308 25 mg Q6W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 0.00 μg/mL |
| Arm G: MK-1308 25 mg Q6W | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 0.00 μg/mL |
| Arm I: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 0.00 μg/mL |
| Arm I: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 0.00 μg/mL |
| Arm I: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 0.00 μg/mL |
| Arm K: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Quavonlimab | Cycle 3 | 0.00 μg/mL |
| Arm K: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Quavonlimab | Cycle 1 | 0.00 μg/mL |
| Arm K: MK-1308A Q6W (Co-form) | Minimum Concentration (Cmin) of Quavonlimab | Cycle 2 | 0.00 μg/mL |
Secondary
Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs)
Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with pembrolizumab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for arm G and cross over phase.
Time frame: Cohorts 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycles 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.
Population: Participants with at least one ADA sample available after treatment with pembrolizumab
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 12 Participants |
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 12 Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 12 Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Non - TE Neutralizing Antibody (NAB) NEG (Negative) | 1 Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 13 Participants |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 5 Participants |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 5 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB Positive (POS) | 1 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 31 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 36 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB NEG | 4 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Inconclusive | 2 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 39 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 33 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB NEG | 4 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 33 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 37 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB Positive (POS) | 1 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB NEG | 3 Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB NEG | 4 Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 31 Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 35 Participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB NEG | 1 Participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 10 Participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 11 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB NEG | 3 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Inconclusive | 5 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 94 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Treatment Boosted (TB) NAB NEG | 1 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 103 Participants |
| Arm I: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 20 Participants |
| Arm I: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 23 Participants |
| Arm I: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Non - TE Neutralizing Antibody (NAB) NEG (Negative) | 1 Participants |
| Arm I: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Inconclusive | 2 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB NEG | 2 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Negative | 13 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Treatment Boosted (TB) NAB NEG | 0 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Inconclusive | 4 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | Evaluable | 20 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs) | TE NAB Positive (POS) | 1 Participants |
Secondary
Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs)
Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with quavonlimab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted (TB)). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase.
Time frame: Cohort 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycle 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, G, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.
Population: Participants with at least one ADA sample available after treatment with quavonlimab
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 11 Participants |
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 14 Participants |
| Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 3 Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 15 Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 7 Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 7 Participants |
| Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TB NAB MISSING | 1 Participants |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 4 Participants |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 8 Participants |
| Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 4 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 23 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 36 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | NON-TE NAB MISSING | 1 Participants |
| Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 12 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 6 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | NON-TE NAB MISSING | 1 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 39 Participants |
| Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 32 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TB NAB MISSING | 1 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 6 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 30 Participants |
| Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 37 Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 8 Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 35 Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Inconclusive | 1 Participants |
| Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 26 Participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 7 Participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 11 Participants |
| Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 4 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Inconclusive | 2 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 102 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | NON-TE NAB MISSING | 1 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 35 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 61 Participants |
| Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TB NAB MISSING | 3 Participants |
| Arm G: MK-1308 25 mg Q6W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Inconclusive | 1 Participants |
| Arm G: MK-1308 25 mg Q6W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TB NAB MISSING | 2 Participants |
| Arm G: MK-1308 25 mg Q6W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 21 Participants |
| Arm G: MK-1308 25 mg Q6W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 38 Participants |
| Arm G: MK-1308 25 mg Q6W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | NON-TE NAB MISSING | 1 Participants |
| Arm G: MK-1308 25 mg Q6W | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 13 Participants |
| Arm I: MK-1308A Q6W (Co-form) | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 8 Participants |
| Arm I: MK-1308A Q6W (Co-form) | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 15 Participants |
| Arm I: MK-1308A Q6W (Co-form) | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 23 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Evaluable | 20 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Negative | 6 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TB NAB MISSING | 2 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | Inconclusive | 1 Participants |
| Arm K: MK-1308A Q6W (Co-form) | Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs) | TE NAB MISSING | 11 Participants |