Clinical Trials /

Study of Vibostolimab Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (MK-7684-001)

NCT02964013

Description:

This is a safety, efficacy, and pharmacokinetics (PK) study of vibostolimab (MK-7684) as monotherapy and in combination with pembrolizumab (MK-3475) or pembrolizumab plus pemetrexed and carboplatin in adults with metastatic solid tumors for which there is no available therapy that is expected to convey clinical benefit. Part A of this study is a dose escalation and confirmation phase to estimate the recommended Phase 2 dose (RPTD) for vibostolimab monotherapy or in combination with pembrolizumab, pemetrexed, and carboplatin. Part A will also evaluate the anti-tumor activity of vibostolimab in combination with pembrolizumab plus pemetrexed and carboplatin in participants with non-small cell lung cancer (NSCLC) and vibostolimab (at two dose levels) in combination with pembrolizumab in Japanese participants with gastric cancer. Part B will evaluate the anti-tumor activity of vibostolimab at the RPTD when used as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors in a non-randomized study design. Part B will also evaluate 2 doses of vibostolimab in combination with pembrolizumab in participants with programmed death 1 (PD-1) treatment naïve cancer using a 1:1 randomized study design. Part B is expanded with Amendment 11 to include an additional arm that will compare the safety and PK of a fixed dose of vibostolimab (+) pembrolizumab coformulation (MK-7684A) to vibostolimab in combination with pembrolizumab administered as separate intravenous infusions. Part A is expanded with Amendment 12 to include an additional arm that will compare the safety and PK of vibostolimab plus pembrolizumab plus the investigator's choice of platinum agent (carboplatin or cisplatin), and etoposide. Part B is expanded with Amendment 12 to include evaluation of efficacy of vibostolimab plus pembrolizumab plus the investigator's choice of platinum agent (carboplatin or cisplatin), and etoposide and efficacy of vibostolimab (+) pembrolizumab coformulation in participants from mainland China. The primary hypotheses are that vibostolimab administered as monotherapy or in combination with pembrolizumab is safe and tolerable when administered at the RPTD and that vibostolimab (+) pembrolizumab coformulation is safe and tolerable when administered as a fixed dose.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Vibostolimab Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (MK-7684-001)
  • Official Title: A Phase 1 Trial of MK-7684 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 7684-001
  • SECONDARY ID: MK-7684-001
  • SECONDARY ID: 194809
  • NCT ID: NCT02964013

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
vibostolimabMK-7684Advanced solid tumor cohort
pembrolizumabKEYTRUDA®Advanced solid tumor cohort
pemetrexedALIMTA®vibostolimab +pembro+pemetrexed+carboplatin
carboplatinPARAPLATIN®vibostolimab +pembro+pemetrexed+carboplatin
MK-7684AMK-7684A
cisplatinPLATINOL-AQ®vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide
etoposideETOPOPHOS®vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide

Purpose

This is a safety, efficacy, and pharmacokinetics (PK) study of vibostolimab (MK-7684) as monotherapy and in combination with pembrolizumab (MK-3475) or pembrolizumab plus pemetrexed and carboplatin in adults with metastatic solid tumors for which there is no available therapy that is expected to convey clinical benefit. Part A of this study is a dose escalation and confirmation phase to estimate the recommended Phase 2 dose (RPTD) for vibostolimab monotherapy or in combination with pembrolizumab, pemetrexed, and carboplatin. Part A will also evaluate the anti-tumor activity of vibostolimab in combination with pembrolizumab plus pemetrexed and carboplatin in participants with non-small cell lung cancer (NSCLC) and vibostolimab (at two dose levels) in combination with pembrolizumab in Japanese participants with gastric cancer. Part B will evaluate the anti-tumor activity of vibostolimab at the RPTD when used as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors in a non-randomized study design. Part B will also evaluate 2 doses of vibostolimab in combination with pembrolizumab in participants with programmed death 1 (PD-1) treatment naïve cancer using a 1:1 randomized study design. Part B is expanded with Amendment 11 to include an additional arm that will compare the safety and PK of a fixed dose of MK-7684A, a co-formulated product of vibostolimab plus pembrolizumab, to vibostolimab in combination with pembrolizumab administered as separate intravenous infusions. Part A is expanded with Amendment 12 to include an additional arm that will compare the safety and PK of MK-7684 plus pembrolizumab plus the investigator's choice of platinum agent (carboplatin or cisplatin), and etoposide. Part B is expanded with Amendment 12 to include evaluation of efficacy of MK-7684 plus pembrolizumab plus the investigator's choice of platinum agent (carboplatin or cisplatin), and etoposide and efficacy of MK-7684A in participants from mainland China. The primary hypotheses are that vibostolimab administered as monotherapy or in combination with pembrolizumab is safe and tolerable when administered at the RPTD and that MK-7684A is safe and tolerable when administered as a fixed dose.

Trial Arms

NameTypeDescriptionInterventions
vibostolimabExperimentalDuring an initial dose evaluation phase, participants will receive Dose A, B, C, D, E, or F of vibostolimab on Day 1 of each 21-day infusion cycle (for a maximum of 35 cycles) until the RPTD has been established. The RPTD will be established based on the number of dose limiting toxicities (DLTs) at each dose level. Once the RPTD is established, participants will continue receiving the RPTD of vibostolimab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
  • vibostolimab
vibostolimab + pembrolizumab (pembro)ExperimentalDuring an initial dose evaluation phase, participants will receive Dose A, B, C, D, E, or F of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle (for a maximum of 35 cycles) until the RPTD of vibostolimab has been established. The RPTD will be established based on the number of DLTs at each dose level. Once the RPTD of vibostolimab is established, participants will continue receiving the RPTD of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
  • vibostolimab
  • pembrolizumab
Advanced solid tumor cohortExperimentalParticipants will receive the RPTD of vibostolimab monotherapy or the RPTD of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
  • vibostolimab
  • pembrolizumab
Randomized dose 1 comparison cohortExperimentalParticipants will be randomized to receive a fixed dose (Dose 1) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
  • vibostolimab
  • pembrolizumab
Randomized dose 2 comparison cohortExperimentalParticipants will be randomized to receive a fixed dose (Dose 2) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
  • vibostolimab
  • pembrolizumab
vibostolimab +pembro+pemetrexed+carboplatinExperimentalParticipants will receive a fixed dose of vibostolimab in combination with 200 mg pembrolizumab, 500 mg/m^2 pemetrexed, and Area Under Curve (AUC) 5 mg/mL/min carboplatin on Day 1 of each 21-day infusion cycle for up to 4 cycles followed by maintenance therapy with a fixed dose of vibostolimab in combination with 200 mg pembrolizumab and 500 mg/m^2 pemetrexed on Day 1 of each 21-day infusion cycle for up to an additional 31 cycles.
  • vibostolimab
  • pembrolizumab
  • pemetrexed
  • carboplatin
vibostolimab Dose 1 Japanese cohortExperimentalJapanese participants will be randomized to receive a fixed dose (Dose 1) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
  • vibostolimab
  • pembrolizumab
vibostolimab Dose 2 Japanese cohortExperimentalJapanese participants will be randomized to receive a fixed dose (Dose 2) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
  • vibostolimab
  • pembrolizumab
MK-7684AExperimentalParticipants will receive a fixed dose of MK-7684A, consisting of 200 mg of vibostolimab + 200 mg pembrolizumab, on Day 1 of each 21-day infusion cycle for up to 35 cycles.
  • MK-7684A
vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposideExperimentalParticipants will receive 200 mg vibostolimab in combination with 200 mg pembrolizumab, plus the investigator's choice of Area Under Curve (AUC) 5 mg/mL/min carboplatin OR 75 mg/m^2 cisplatin on Day 1 of each 21-day cycle plus 100 mg/m^2/day etoposide on Days 1-3 of each 21-day cycle for up to 4 cycles. Maintenance therapy with 200 mg vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day cycle will continue for up to an additional 31 cycles. A participant will be allowed to switch from cisplatin to carboplatin in the event of an adverse event (AE), ineligibility for further cisplatin therapy, and/or the investigator considers switching to carboplatin to be in the best interest of the participant.
  • carboplatin
  • cisplatin
  • etoposide
MK-7684A China cohortExperimentalParticipants from mainland China will receive a fixed dose of MK-7684A, consisting of 200 mg of vibostolimab + 200 mg pembrolizumab, on Day 1 of each 21-day infusion cycle for up to 35 cycles.
  • MK-7684A

Eligibility Criteria

        Inclusion Criteria:

          -  For Part A participants enrolled prior to Amendment 7, must have a histologically or
             cytologically confirmed metastatic solid tumor for which there is no available therapy
             that is expected to convey clinical benefit

          -  For Part A Japanese cohort added with Amendment 7: Must reside in Japan and be of
             Japanese descent and have adenocarcinoma of the stomach and/or gastric-esophageal
             junction (GEJ) that is considered inoperable and that has received, and progressed on,
             at least 1 prior chemotherapy regimen or human epidermal growth factor receptor 2
             (HER2)/neu-targeted approved therapy (if HER2/neu-positive). In both cases,
             participants may be untreated or could have received and progressed on 1 prior
             regimen, but must not have received prior anti-PD-1/PD-L1 therapy

          -  For Part A participants with non-small cell lung cancer (NSCLC) added with Amendment
             7: Must have a histologically or cytologically confirmed diagnosis of stage IV (M1a or
             M1b per current American Joint Committee on Cancer criteria, edition 8) non-squamous
             NSCLC

          -  For Part B China participants added with Amendment 12. Must have a histologically or
             cytologically confirmed metastatic solid tumor for which no more than 2 prior lines of
             therapy were administered and there is no available therapy that is expected to convey
             clinical benefit AND be Chinese from mainland China

          -  For Parts A and B: Has histologically or cytologically confirmed metastatic solid
             tumor

          -  Has measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST)

          -  Has an Eastern Cooperative Oncology Group performance status of 0 to 1

          -  Females must not be pregnant

          -  Women of childbearing potential and male participants must agree to use adequate
             contraception for the course of the study

          -  Has provided a tumor tissue sample (archival or newly obtained core or excisional
             biopsy of a tumor lesion)

          -  For Chinese participants enrolled as part of Amendment 12. No tumor tissue samples
             will be collected

        Exclusion Criteria:

          -  Has had chemotherapy, radiation, biological cancer therapy or major surgery within 4
             weeks prior to the first dose of study treatment

          -  Has not recovered to Common Toxicity Criteria for Adverse Events Grade 1 or better
             from the adverse events due to cancer therapeutics administered more than 4 weeks
             prior to the first dose of study treatment

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment

          -  Has received previous treatment with another agent targeting the T cell immunoglobulin
             and immunoreceptor tyrosine-based inhibitory motif (TIGIT) receptor

          -  Has received previous treatment with an immunomodulatory agent (e.g., anti-programmed
             cell death 1, anti-programmed cell death ligand 1 or cytotoxic T-lymphocyte-associated
             protein 4) and was discontinued from that treatment due to a Grade 3 or higher
             immune-related adverse event

          -  Is expected to require any other form of antineoplastic therapy while participating in
             the trial

          -  Is on chronic systemic steroid therapy in excess of replacement doses or on any other
             form of immunosuppressive medication

          -  Has a history of a previous additional malignancy unless potentially curative
             treatment has been completed with no evidence of malignancy for 5 years

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has an active autoimmune disease

          -  Has an active infection requiring systemic treatment

          -  Has interstitial lung disease

          -  Has active or past history of (non-infectious) pneumonitis requiring steroids

          -  Has symptomatic ascites or pleural effusion

          -  Has previously had a hematopoetic stem cell transplant or solid organ transplant

          -  Is known to be human immunodeficiency virus (HIV) positive and/or known to have active
             chronic or acute Hepatitis B or Hepatitis C

          -  Has a known psychiatric and/or substance abuse disorder that would make it difficult
             for the participant to cooperate with the requirements of the trial

          -  Is a regular user (including recreational use) of any illicit drugs at the time of
             providing documented informed consent, or has a recent history (within the last year)
             of substance abuse

          -  Has received a live virus vaccine within 30 days prior to the first dose of study
             treatment

          -  Has had hormonal cancer therapy (e.g., tamoxifen, leuprolide). within 4 weeks prior to
             the first dose of study treatment

          -  For Part A participants with NSCLC added with Amendment 7: Is unable to interrupt
             aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) other than an aspirin
             dose ≤1.3 gram per day for a 5-day period (8-day period for long-acting agents, such
             as piroxicam)

          -  For Part A participants with NSCLC added with Amendment 7: Is unable or unwilling to
             take folic acid or Vitamin B12 supplementation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose Limiting Toxicities (DLTs)
Time Frame:Up to 24 Months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame:Up to 24 Months
Safety Issue:
Description:
Measure:Area Under the Concentration-Time Curve
Time Frame:Cycle 1 Day 1: pre-dose, 0.5, and 2 hours post-dose. Cycle length= 21 days.
Safety Issue:
Description:
Measure:Maximum Plasma Concentration (Cmax)
Time Frame:Cycle 1 Day 1: pre-dose, 0.5, and 2 hours post-dose. Cycle length= 21 days.
Safety Issue:
Description:
Measure:Trough Concentration (CTrough)
Time Frame:Cycle 1 Day 1: pre-dose, 0.5, and 2 hours post-dose. Cycle length= 21 days.
Safety Issue:
Description:
Measure:Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
Time Frame:At the end of Cycle 1 (cycle length is 21 days)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death Receptor 1 (PD-1)
  • Programmed Cell Death Receptor Ligand 1 (PD-L1)
  • Programmed Cell Death Receptor Ligand 2 (PD-L2)
  • PD-1
  • PDL1
  • PD-L1
  • PD-L2

Last Updated

December 1, 2020