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Study of Quavonlimab (MK-1308) in Combination With Pembrolizumab (MK-3475) in Advanced Solid Tumors (MK-1308-001)

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ClinicalTrials.gov Identifier: NCT03179436
Recruitment Status : Recruiting
First Posted : June 7, 2017
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Biological: Quavonlimab Biological: Pembrolizumab Drug: Pembrolizumab/Quavonlimab Phase 1 Phase 2

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, PD-1/L1 refractory advanced melanoma, and participants from mainland China.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 388 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 / 2 Open Label, Multi-Arm, Multicenter Study of MK-1308 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
Actual Study Start Date : July 2, 2017
Estimated Primary Completion Date : December 27, 2023
Estimated Study Completion Date : December 27, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Escalation: Dose Level (DL) 1 Quavonlimab + Pembro: Cohort 1
On Cycle 1, Day 1 of the Dose Escalation Phase, advanced solid tumor participants receive a single monotherapy dose lead-in with quavonlimab at dose level 1 (DL1). On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL1 in combination with pembrolizumab (pembro) at pembrolizumab dose level 1 (PDL1) according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study.
Biological: Quavonlimab
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.
Other Name: MK-1308

Biological: Pembrolizumab
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).
Other Name: Keytruda®

Experimental: Escalation: DL 2 Quavonlimab + Pembro: Cohort 2
On Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL2. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study.
Biological: Quavonlimab
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.
Other Name: MK-1308

Biological: Pembrolizumab
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).
Other Name: Keytruda®

Experimental: Escalation: DL 3 Quavonlimab + Pembro: Cohort 3
On Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL3. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL3 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study.
Biological: Quavonlimab
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.
Other Name: MK-1308

Biological: Pembrolizumab
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).
Other Name: Keytruda®

Experimental: Confirmation: DL 1 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm A
On Cycle 1, Day 1 of the Dose Confirmation Phase and during all subsequent cycles, participants with NSCLC receive quavonlimab at DL1 in combination with pembrolizumab at PDL1, both according to Schedule 1. Participants will be treated for up to 35 cycles total on study.
Biological: Quavonlimab
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.
Other Name: MK-1308

Biological: Pembrolizumab
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).
Other Name: Keytruda®

Experimental: Confirmation: DL 1 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm B
On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive quavonlimab at DL1 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and quavonlimab at DL1 according to Schedule 2. Participants will be treated for up to 35 cycles total on study.
Biological: Quavonlimab
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.
Other Name: MK-1308

Biological: Pembrolizumab
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).
Other Name: Keytruda®

Experimental: Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (NSCLC): Arm C
On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and at DL2 quavonlimab according to Schedule 2. Participants will be treated for up to 35 cycles total on study.
Biological: Quavonlimab
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.
Other Name: MK-1308

Biological: Pembrolizumab
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).
Other Name: Keytruda®

Experimental: Confirmation: DL 2 Quavonlimab Schedule 2 + Pembro (SCLC): Arm D
On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with SCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and quavonlimab at DL2 according to Schedule 2. Participants will be treated for up to 35 cycles total on study.
Biological: Quavonlimab
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.
Other Name: MK-1308

Biological: Pembrolizumab
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).
Other Name: Keytruda®

Experimental: Confirmation: DL 2 Quavonlimab Schedule 1 + Pembro (NSCLC): Arm E
On Cycle 1, Day 1 of the Dose Confirmation Phase and during all subsequent cycles, participants with NSCLC receive quavonlimab at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. Participants will be treated for up to 35 cycles total on study.
Biological: Quavonlimab
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.
Other Name: MK-1308

Biological: Pembrolizumab
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).
Other Name: Keytruda®

Experimental: Expansion: DL1 Quavonlimab Schedule 2+PDL2 Pembro Schedule 2: Arm F
On Cycle 1, Day 1 of the Efficacy Expansion Phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma receive quavonlimab at DL1 in combination with pembrolizumab at pembrolizumab dose level 2 (PDL2). Both quavonlimab and pembrolizumab will be administered according to Schedule 2 for up to 24 months on study.
Biological: Quavonlimab
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.
Other Name: MK-1308

Biological: Pembrolizumab
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).
Other Name: Keytruda®

Experimental: Expansion: DL1 Quavonlimab Schedule 2 Monotherapy: Arm G
On Cycle 1, Day 1 of the Efficacy Expansion Phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma receive quavonlimab at DL1 according to Schedule 2 for up to 24 months on study. Participants who demonstrate radiographically confirmed progressive disease in Arm G will be eligible to receive combination therapy with pembrolizumab (crossover).
Biological: Quavonlimab
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.
Other Name: MK-1308

Experimental: Coformulation: Pembrolizumab/Quavonlimab Schedule 2: Arm I
On Cycle 1, Day 1 of the Coformulation Phase and during all subsequent cycles, participants with advanced/metastatic solid tumors receive pembrolizumab/quavonlimab according to Schedule 2 for up to 24 months on study.
Drug: Pembrolizumab/Quavonlimab
Pembrolizumab/Quavonlimab is a coformulated product composed of quavonlimab at DL1 in combination with pembrolizumab at dose level 2 (PDL2).
Other Name: MK-1308A

Experimental: Coformulation Phase: Pembrolizumab/Quavonlimab Schedule 2: Arm J
On Cycle 1, Day 1 of the Coformulation Phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma receive pembrolizumab/quavonlimab according to Schedule 2 for up to 24 months on study.
Drug: Pembrolizumab/Quavonlimab
Pembrolizumab/Quavonlimab is a coformulated product composed of quavonlimab at DL1 in combination with pembrolizumab at dose level 2 (PDL2).
Other Name: MK-1308A

Experimental: Coformulation Phase in China: Pembrolizumab/Quavonlimab Schedule 2: Arm K
On Cycle 1, Day 1 of the Coformulation Phase and during all subsequent cycles, participants in mainland China with advanced solid tumors receive pembrolizumab/quavonlimab according to Schedule 2 for up to 24 months on study.
Drug: Pembrolizumab/Quavonlimab
Pembrolizumab/Quavonlimab is a coformulated product composed of quavonlimab at DL1 in combination with pembrolizumab at dose level 2 (PDL2).
Other Name: MK-1308A




Primary Outcome Measures :
  1. Number of participants with a Dose Limiting Toxicity (DLT) [ Time Frame: Up to 6 weeks ]
    DLTs will be assessed during the first 6 weeks (2 cycles) of treatment for the Dose Escalation and the first 3 weeks (1 cycle) of treatment for the Dose Confirmation. DLT is 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.

  2. Number of participants with ≥1 adverse event (AE) [ Time Frame: Up to ~2.5 years ]
    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.

  3. Number of participants discontinuing study treatment due to an AE [ Time Frame: Up to ~2 years ]
    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.

  4. Efficacy Expansion: Number of participants with ≥1 AE [ Time Frame: Up to ~2.5 years ]
    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.

  5. Efficacy Expansion: Number of participants discontinuing study treatment due to an AE [ Time Frame: Up to ~2 years ]
    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

  6. Coformulation: Number of participants with ≥1 DLT [ Time Frame: Up to 6 weeks ]
    DLTs will be assessed during the first 6 weeks of treatment for the Coformulation Phase (Arm I). A DLT is 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 of the Coformulation Phase 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.

  7. Coformulation: Number of participants with ≥1 AE [ Time Frame: Up to ~2.5 years ]
    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.

  8. Coformulation: Number of participants discontinuing study treatment due to an AE [ Time Frame: Up to ~2 years ]
    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.

  9. Efficacy Expansion and Coformulation: 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) [ Time Frame: Up to ~4 years ]
    ORR is defined as the percentage of participants in the analysis population whose best overall response (BOR) is confirmed complete response (CR) or partial response (PR) as assessed by BICR and based on imaging per adjusted RECIST 1.1. Tumor responses evaluated using adjusted RECIST 1.1 follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and require confirmation per RECIST 1.1. According to adjusted RECIST 1.1, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR according to adjusted RECIST 1.1 is at least a 30% decrease in the sum of diameters (SOD) of target lesions as assessed by the investigator, taking as reference the baseline SOD.


Secondary Outcome Measures :
  1. Area under the plasma concentration time curve (AUC) of pembrolizumab [ Time Frame: At designated timepoints (up to ~6 months) ]
    AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.

  2. Maximum concentration (Cmax) of pembrolizumab [ Time Frame: At designated timepoints (up to ~6 months) ]
    Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.

  3. Minimum concentration (Cmin) of pembrolizumab [ Time Frame: At designated timepoints (up to ~6 months) ]
    Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points (pre-dose) to assess the Cmin of pembrolizumab.

  4. Number of participants with pembrolizumab anti-drug antibodies (ADAs) [ Time Frame: At designated timepoints (up to ~2 years) ]
    Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab ADAs. The number of participants who develop pembrolizumab ADAs will be reported.

  5. AUC of quavonlimab [ Time Frame: At designated timepoints (up to ~6 months) ]
    AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.

  6. Cmax of quavonlimab [ Time Frame: At designated timepoints (up to ~6 months) ]
    Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.

  7. Cmin of quavonlimab [ Time Frame: At designated timepoints (up to ~6 months) ]
    Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points (pre-dose) to assess the Cmin of quavonlimab.

  8. Number of participants with quavonlimab ADAs [ Time Frame: At designated timepoints (up to ~2 years) ]
    Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab ADAs. The number of participants who develop quavonlimab ADAs will be reported.

  9. Chinese Cohort: AUC of pembrolizumab [ Time Frame: At designated timepoints (up to ~6 months) ]
    AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.

  10. Chinese Cohort: Cmax of pembrolizumab [ Time Frame: At designated timepoints (up to ~6 months) ]
    Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.

  11. Chinese Cohort: Cmin of pembrolizumab [ Time Frame: At designated timepoints (up to ~6 months) ]
    Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points (pre-dose) to assess the Cmin of pembrolizumab.

  12. Chinese Cohort: Number of participants with pembrolizumab ADAs [ Time Frame: At designated timepoints (up to ~2 years) ]
    Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab ADAs. The number of participants who develop pembrolizumab ADAs will be reported.

  13. Chinese Cohort: AUC of quavonlimab [ Time Frame: At designated timepoints (up to ~6 months) ]
    AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.

  14. Chinese Cohort: Cmax of quavonlimab [ Time Frame: At designated timepoints (up to ~6 months) ]
    Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.

  15. Chinese Cohort: Cmin of quavonlimab [ Time Frame: At designated timepoints (up to ~6 months) ]
    Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points (pre-dose) to assess the Cmin of quavonlimab.

  16. Chinese Cohort: Number of participants with quavonlimab ADAs [ Time Frame: At designated timepoints (up to ~2 years) ]
    Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab ADAs. The number of participants who develop quavonlimab ADAs will be reported.

  17. Dose Escalation, Dose Confirmation, Coformulation: ORR as assessed by investigator based on adjusted RECIST v1.1 [ Time Frame: Up to ~4 years ]
    ORR is defined as the percentage of participants in the analysis population whose BOR is confirmed CR or PR as assessed by investigator and based on imaging per adjusted RECIST 1.1. Tumor responses evaluated using adjusted RECIST 1.1 follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and require confirmation per RECIST 1.1. According to adjusted RECIST 1.1, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR according to adjusted RECIST 1.1 is at least a 30% decrease in the SOD of target lesions as assessed by the investigator, taking as reference the baseline SOD.

  18. Efficacy Expansion and Coformulation: Duration of Response (DOR) as assessed by BICR based on adjusted RECIST v1.1 [ Time Frame: Up to ~4 years ]
    DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first (for responders only).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 and Coformulation Phase Arm J:

  • 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, G, and J 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 J and 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03179436


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
Publications of Results:
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03179436    
Other Study ID Numbers: 1308-001
MK-1308-001 ( Other Identifier: Merck )
173820 ( Registry Identifier: JAPIC-CTI )
2019-003703-35 ( EudraCT Number )
First Posted: June 7, 2017    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death Protein 1 (PD-1, PD1),
Programmed Cell Death Ligand 1 (PD-L1, PDL1)
Programmed Cell Death Ligand 2 (PD-L2, PDL2)
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents