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Safety, Pharmacokinetics (PK), and Efficacy of MK-1308 in Combination With Pembrolizumab 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 : December 6, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE May 31, 2017
First Posted Date  ICMJE June 7, 2017
Last Update Posted Date December 6, 2019
Actual Study Start Date  ICMJE July 2, 2017
Estimated Primary Completion Date October 24, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 27, 2019)
  • 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.
  • Number of participants with ≥1 adverse event (AE) [ Time Frame: Up to approximately 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.
  • Number of participants discontinuing study treatment due to an AE [ Time Frame: Up to approximately 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.
  • Efficacy Expansion: Number of participants with ≥1 AE [ Time Frame: Up to approximately 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.
  • Efficacy Expansion: Number of participants discontinuing study treatment due to an AE [ Time Frame: Up to approximately 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
  • Efficacy Expansion: Objective Response Rate (ORR) as assessed by blinded independent central review (BICR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to approximately 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 modified RECIST 1.1. Tumor responses evaluated using modified 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 modified 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 modified 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 5, 2017)
  • Number of participants with a Dose Limiting Toxicity (DLT) [ Time Frame: Up to 6 weeks ]
    DLTs will be assessed during the first 6 weeks of treatment for all phases of the study and are defined as toxicities that meet pre-defined severity criteria, that are possibly, probably, or definitely related to study therapy, and may result in a change in the given dose. These toxicities include Grade 4 non-hematologic toxicity (not laboratory); Grade 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥Grade 3 in severity; any Grade 3 or Grade 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; Grade 3 or Grade 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during Cycle 1 or 2, and Grade 5 toxicity.
  • Number of participants with ≥1 adverse event (AE) [ Time Frame: Up to 3 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.
  • Number of participants discontinuing study treatment due to an AE [ Time Frame: Up to 24 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.
Change History Complete list of historical versions of study NCT03179436 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2019)
  • Dose Escalation: Area under the plasma concentration time curve (AUC) of MK-1308 at steady state [ Time Frame: Cycles 1, 2 and 3: end of infusion (up to approximately 30 minutes), Day 8, and Day 15. Cycles 5 and 9: end of infusion (up to 30 minutes). Cycle = 21 days ]
    AUC is the area under the plot of plasma concentration of drug against time after drug administration and is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs. Blood samples will be collected at multiple time points during the Dose Escalation phase to assess the AUC of MK-1308.
  • Dose Escalation: Minimum concentration (Cmin) of MK-1308 at steady state [ Time Frame: Pre-dose Cycles 1, 2, 3, 5, 6, 7, 9 and every 4 cycles up to 2 years. Cycle = 21 days ]
    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) during the Dose Escalation phase to assess the Cmin of MK-1308.
  • Dose Escalation: Maximum concentration (Cmax) of MK-1308 at steady state [ Time Frame: Cycles 1, 2 and 3: end of infusion (up to approximately 30 minutes), Day 8, and Day 15. Cycles 5 and 9: end of infusion (up to 30 minutes). Cycle = 21 days ]
    Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points during the Dose Escalation phase to assess the Cmax of MK-1308.
  • Dose Confirmation: AUC of MK-1308 at steady state [ Time Frame: Cycles 1, 2, 3: end of infusion (up to approximately 30 minutes), Day 8, and Day 15. Cycle 4 and 8: end of infusion (up to 30 minutes). Cycle = 21 days ]
    AUC is the area under the plot of plasma concentration of drug against time after drug administration and is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs. Blood samples will be collected at multiple time points during the Dose Confirmation phase to assess the AUC of MK-1308.
  • Dose Confirmation: Cmin of MK-1308 at steady state [ Time Frame: Pre-dose cycles 1, 2, 3, 4, 5, 6, 8, and every 4 cycles up to 2 years. Cycle = 21 days ]
    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) during the Dose Confirmation phase to assess the Cmin of MK-1308.
  • Dose Confirmation: Cmax of MK-1308 at steady state [ Time Frame: Cycles 1, 2, 3: end of infusion (up to approximately 30 minutes), Day 8, and Day 15. Cycle 4 and 8: end of infusion (up to 30 minutes). Cycle = 21 days ]
    Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points during the Dose Confirmation phase to assess the Cmax of MK-1308.
  • Dose Escalation and Dose Confirmation: ORR as assessed by investigator based on modified RECIST 1.1 [ Time Frame: Up to approximately 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 modified RECIST 1.1. Tumor responses evaluated using modified 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 modified 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 modified 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.
  • Efficacy Expansion: Duration of Response (DOR) as assessed by BICR based on modified RECIST 1.1 [ Time Frame: Up to approximately 4 years ]
    DOR was 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2017)
  • Dose Escalation: Area under the plasma concentration time curve (AUC) of MK-1308 at steady state [ Time Frame: pre-dose Cycles 1, 2, 3, 5, 6, 7, 9 and every 4 cycles up to 3 years, postdose (30 min): cycles 1, 2, 3, 5, and 9, Days 8 and 15 of cycles 1, 2, & 3. Cycle = 21 days ]
    AUC is the area under the plot of plasma concentration of drug against time after drug administration and is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs. Blood samples will be collected at multiple time points (pre-dose and post-dose) during the Dose Escalation phase to assess the AUC of MK-1308.
  • Dose Escalation: Minimum concentration (Cmin) of MK-1308 at steady state [ Time Frame: pre-dose Cycles 1, 2, 3, 5, 6, 7, 9 and every 4 cycles up to 3 years, postdose (30 min): cycles 1, 2, 3, 5, and 9, Days 8 and 15 of cycles 1, 2, & 3. Cycle = 21 days ]
    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 and post-dose) during the Dose Escalation phase to assess the Cmin of MK-1308.
  • Dose Escalation: Maximum concentration (Cmax) of MK-1308 at steady state [ Time Frame: pre-dose Cycles 1, 2, 3, 5, 6, 7, 9 and every 4 cycles up to 3 years, postdose (30 min): cycles 1, 2, 3, 5, and 9, Days 8 and 15 of cycles 1, 2, & 3. Cycle = 21 days ]
    Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points (pre-dose and post-dose) during the Dose Escalation phase to assess the Cmax of MK-1308.
  • Dose Confirmation: AUC of MK-1308 at steady state [ Time Frame: pre-dose cycles 1, 2, 3, 4, 5, 6, 8, and every 4 cycles up to 3 years, post-dose (30 min): cycles 1, 2, 3, 4, and 8, Days 8 & 15 in cycles 1, 2, & 3. Cycle = 21 days ]
    AUC is the area under the plot of plasma concentration of drug against time after drug administration and is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs. Blood samples will be collected at multiple time points (pre-dose and post-dose) during the Dose Confirmation phase to assess the AUC of MK-1308.
  • Dose Confirmation: Cmin of MK-1308 at steady state [ Time Frame: pre-dose cycles 1, 2, 3, 4, 5, 6, 8, and every 4 cycles up to 3 years, post-dose (30 min): cycles 1, 2, 3, 4, and 8, Days 8 & 15 in cycles 1, 2, & 3. Cycle = 21 days ]
    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 and post-dose) during the Dose Confirmation phase to assess the Cmin of MK-1308.
  • Dose Confirmation: Cmax of MK-1308 at steady state [ Time Frame: pre-dose cycles 1, 2, 3, 4, 5, 6, 8, and every 4 cycles up to 3 years, post-dose (30 min): cycles 1, 2, 3, 4, and 8, Days 8 & 15 in cycles 1, 2, & 3. Cycle = 21 days ]
    Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points (pre-dose and post-dose) during the Dose Confirmation phase to assess the Cmax of MK-1308.
  • Objective Response Rate (ORR) as assessed by investigator based on RECIST 1.1 [ Time Frame: Up to 3 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) based on imaging per RECIST 1.1. According to 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 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.
  • ORR as assessed by investigator based on immune-related RECIST (irRECIST) in conjunction with RECIST 1.1 [ Time Frame: Up to 3 years ]
    ORR is defined as the percentage of participants whose best response based on imaging is CR or PR per irRECIST. irRECIST is a modification to RECIST that takes into account unique patterns of atypical response in immunotherapy and enables treatment beyond initial radiographic progression. The irRECIST modification to RECIST is used in conjunction with RECIST 1.1 to determine the BOR. At initial PD by RECIST 1.1, if participant is clinically stable the investigator may continue to treat and scan again ≥4 weeks later to see if PD confirmed. CR is disappearance of all lesions (target, non-target, and new lesions if any had appeared). PR is a decrease of ≥30% in the SOD of target lesions from baseline, with no indication of further progression by non-target or new lesions. BOR during irRECIST portion is the most favorable visit response observed, with no confirmation requirement. BOR for the participant overall is the more favorable of the RECIST 1.1 (pre-PD) and irRECIST (post-PD) BORs.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Pharmacokinetics (PK), and Efficacy of MK-1308 in Combination With Pembrolizumab in Advanced Solid Tumors (MK-1308-001)
Official Title  ICMJE A Phase 1 Open Label, Multi-Arm, Multicenter Study of MK-1308 in Combination With Pembrolizumab for Subjects With Advanced Solid Tumors
Brief Summary This study will assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of MK-1308 when used in combination with pembrolizumab in participants with advanced solid tumors.
Detailed Description

After screening, participants are assigned to either the Dose Escalation Phase or Dose Confirmation Phase. The Dose Escalation Phase consists of 3 cohorts and will evaluate available PK and safety data from the first 6 participants of each cohort, including dose limiting toxicities (DLTs). The purpose of the Dose Confirmation Phase is to gather additional safety, tolerability, PK, and preliminary efficacy data of MK-1308 in combination with pembrolizumab. The 5 arms of the Dose Confirmation Phase will include advanced/metastatic non-small cell lung cancer (NSCLC) and second line advanced/metastatic small cell lung cancer (SCLC). In participants who have initial evidence of radiological progressive disease (PD) by modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, it will be at the discretion of the investigator whether to continue a participant on study treatment until repeat imaging is obtained.

Protocol Amendment 4 will enroll participants with melanoma in a limited Efficacy Expansion Cohort. During the Efficacy Expansion Phase, participants will be randomized to receive either MK-1308 in combination with pembrolizumab or MK-1308 monotherapy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Biological: MK-1308
    MK-1308 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.
  • 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®
Study Arms  ICMJE
  • Experimental: Escalation: Dose Level (DL) 1 MK-1308 + 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 MK-1308 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 MK-1308 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.
    Interventions:
    • Biological: MK-1308
    • Biological: Pembrolizumab
  • Experimental: Escalation: DL 2 MK-1308 + 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 MK-1308 at DL2. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive MK-1308 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.
    Interventions:
    • Biological: MK-1308
    • Biological: Pembrolizumab
  • Experimental: Escalation: DL 3 MK-1308 + 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 MK-1308 at DL3. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive MK-1308 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.
    Interventions:
    • Biological: MK-1308
    • Biological: Pembrolizumab
  • Experimental: Confirmation: DL 1 MK-1308 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 MK-1308 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.
    Interventions:
    • Biological: MK-1308
    • Biological: Pembrolizumab
  • Experimental: Confirmation: DL 1 MK-1308 Schedule 2 + Pembro (NSCLC): Arm B
    On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive MK-1308 at DL1 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and MK-1308 at DL1 according to Schedule 2. Participants will be treated for up to 35 cycles total on study.
    Interventions:
    • Biological: MK-1308
    • Biological: Pembrolizumab
  • Experimental: Confirmation: DL 2 MK-1308 Schedule 2 + Pembro (NSCLC): Arm C
    On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with NSCLC receive MK-1308 at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and MK-1308 at DL2 according to Schedule 2. Participants will be treated for up to 35 cycles total on study.
    Interventions:
    • Biological: MK-1308
    • Biological: Pembrolizumab
  • Experimental: Confirmation: DL 2 MK-1308 Schedule 2 + Pembro (SCLC): Arm D
    On Cycle 1, Day 1 of the Dose Confirmation Phase, participants with SCLC receive MK-1308 at DL2 in combination with pembrolizumab at PDL1. On all subsequent cycles, participants receive pembrolizumab at PDL1 according to Schedule 1 and MK-1308 at DL2 according to Schedule 2. Participants will be treated for up to 35 cycles total on study.
    Interventions:
    • Biological: MK-1308
    • Biological: Pembrolizumab
  • Experimental: Confirmation: DL 2 MK-1308 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 MK-1308 at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. Participants will be treated for up to 35 cycles total on study.
    Interventions:
    • Biological: MK-1308
    • Biological: Pembrolizumab
  • Experimental: Expansion: DL1 MK-1308 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 melanoma receive MK-1308 at DL1 in combination with pembrolizumab at pembrolizumab dose level 2 (PDL2). Both MK-1308 and pembrolizumab will be administered according to Schedule 2 for up to 24 months on study.
    Interventions:
    • Biological: MK-1308
    • Biological: Pembrolizumab
  • Experimental: Expansion: DL1 MK-1308 Schedule 2 Monotherapy: Arm G
    On Cycle 1, Day 1 of the Efficacy Expansion Phase and during all subsequent cycles, participants with melanoma receive MK-1308 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).
    Intervention: Biological: MK-1308
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 14, 2018)
308
Original Estimated Enrollment  ICMJE
 (submitted: June 5, 2017)
148
Estimated Study Completion Date  ICMJE October 24, 2022
Estimated Primary Completion Date October 24, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Female participants of childbearing potential must have negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study treatment and 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
  • 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. 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 Stage 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
  • BRAF V600 mutation-positive melanoma participants may 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

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 only:

  • 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 MK-1308.
  • 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) ONLY:

  • 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 non-infectious 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-virus 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 study medication(s)
  • Has not fully recovered from any effects of major surgery without significant detectable infection

For Efficacy Expansion Phase Arms (F and G) 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
  • Has not discontinued steroid treatment for an irAE for at least 2 weeks prior to the first dose of study drug
  • Has ocular melanoma
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Australia,   Israel,   Japan,   Korea, Republic of,   New Zealand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03179436
Other Study ID Numbers  ICMJE 1308-001
MK-1308-001 ( Other Identifier: Merck Registration Number )
173820 ( Registry Identifier: JAPIC-CTI )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP