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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 : August 2, 2019
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 MK-1308 when used in combination with pembrolizumab in participants with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Biological: MK-1308 Biological: Pembrolizumab Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 308 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open Label, Multi-Arm, Multicenter Study of MK-1308 in Combination With Pembrolizumab for Subjects With Advanced Solid Tumors
Actual Study Start Date : July 2, 2017
Estimated Primary Completion Date : February 16, 2023
Estimated Study Completion Date : February 16, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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®

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.
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®

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.
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®

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.
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®

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.
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®

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.
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®

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.
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®

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.
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®

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.
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®

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).
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.




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 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.

  3. 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.

  4. Efficacy Expansion: Number of participants with ≥1 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.

  5. Efficacy Expansion: Number of participants that discontinue 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

  6. Efficacy Expansion: Objective Response Rate (ORR) as assessed by blinded independent central review (BICR) based on modified 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) 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Dose Escalation and Dose Confirmation: ORR as assessed by investigator based on modified RECIST 1.1 [ Time Frame: Up to 3 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.

  8. Dose Escalation and Dose Confirmation: 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.

  9. Efficacy Expansion: Duration of Response (DOR) as assessed by BICR based on modified RECIST 1.1 [ Time Frame: Up to 3 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).



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.


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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
  • 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 as confirmed 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 Stage IV disease must have progressed on treatment with an anti-PD1/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
  • Have submitted pre-trial imaging and provided a baseline tumor sample

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 ocular melanoma
  • Has uvular melanoma

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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United States, Arizona
Banner MD Anderson Cancer Center ( Site 0013) Active, not recruiting
Gilbert, Arizona, United States, 85234
United States, New Jersey
John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0005) Active, not recruiting
Hackensack, New Jersey, United States, 07601
United States, Tennessee
Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 0004) Active, not recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001) Active, not recruiting
San Antonio, Texas, United States, 78229
Australia, New South Wales
Blacktown Hospital. Western Sydney local health district ( Site 0009) Recruiting
Blacktown, New South Wales, Australia, 2148
Contact: Study Coordinator    +61298818421      
Australia, South Australia
Ashford Cancer Centre Research ( Site 0012) Recruiting
Kurralta Park, South Australia, Australia, 5037
Contact: Study Coordinator    +61882922220      
Israel
Rambam Medical Center ( Site 0003) Recruiting
Haifa, Israel, 3109601
Contact: Study Coordinator    +97247776738      
Hadassah Ein Karem Hebrew University Medical Center ( Site 0021) Recruiting
Jerusalem, Israel, 9112001
Contact: Study Coordinator    +97226776781      
Sheba Medical Center - Cancer Center ( Site 0002) Recruiting
Ramat-Gan, Israel, 5266202
Contact: Study Coordinator    +9725302513      
Japan
National Cancer Center Hospital East ( Site 0014) Active, not recruiting
Kashiwa, Chiba, Japan, 277-8577
Hyogo Cancer Center ( Site 0015) Active, not recruiting
Akashi, Hyogo, Japan, 673-8558
Korea, Republic of
Asan Medical Center ( Site 0006) Active, not recruiting
Seoul., Korea, Republic of, 05505
Seoul National University Hospital ( Site 0007) Active, not recruiting
Seoul, Korea, Republic of, 03080
Severance Hospital Yonsei University Health System ( Site 0008) Active, not recruiting
Seoul, Korea, Republic of, 03722
Samsung Medical Center ( Site 0010) Active, not recruiting
Seoul, Korea, Republic of, 06351
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03179436     History of Changes
Other Study ID Numbers: 1308-001
MK-1308-001 ( Other Identifier: Merck Registration Number )
173820 ( Registry Identifier: JAPIC-CTI )
First Posted: June 7, 2017    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: July 2019
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 Death-1 (PD-1, PD1),
Programmed Death-Ligand 1 (PD-L1, PDL1)

Additional relevant MeSH terms:
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Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents