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

Study Overview
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Brief Summary
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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 pembrolizumab/vibostolimab 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 pembrolizumab/vibostolimab 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 pembrolizumab/vibostolimab coformulation is safe and tolerable when administered as a fixed dose.

Official Title
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A Phase 1 Trial of MK-7684 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

Conditions
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Neoplasms

Intervention / Treatment
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* Biological: vibostolimab
* Biological: pembrolizumab
* Drug: pemetrexed
* Drug: carboplatin
* Biological: pembrolizumab/vibostolimab coformulation
* Drug: cisplatin
* Drug: etoposide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vibostolimab<br>During 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. | Biological: vibostolimab<br>* Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684;|
| Experimental: vibostolimab + pembrolizumab<br>During 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. | Biological: vibostolimab<br>* Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684;Biological: pembrolizumab<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-3475;|
| Experimental: Advanced solid tumor cohort<br>Participants 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. | Biological: vibostolimab<br>* Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684;Biological: pembrolizumab<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-3475;|
| Experimental: Randomized dose 1 comparison cohort<br>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. | Biological: vibostolimab<br>* Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684;Biological: pembrolizumab<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-3475;|
| Experimental: Randomized dose 2 comparison cohort<br>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. | Biological: vibostolimab<br>* Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684;Biological: pembrolizumab<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-3475;|
| Experimental: vibostolimab +pembrolizumab+pemetrexed+carboplatin<br>Participants 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. | Biological: vibostolimab<br>* Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684;Biological: pembrolizumab<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-3475;Drug: pemetrexed<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: ALIMTA®;Drug: carboplatin<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4<br>* Other names: PARAPLATIN®;|
| Experimental: vibostolimab Dose 1 Japanese cohort<br>Japanese 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. | Biological: vibostolimab<br>* Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684;Biological: pembrolizumab<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-3475;|
| Experimental: vibostolimab Dose 2 Japanese cohort<br>Japanese 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. | Biological: vibostolimab<br>* Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684;Biological: pembrolizumab<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-3475;|
| Experimental: pembrolizumab/vibostolimab coformulation<br>Participants will receive a fixed dose of pembrolizumab/vibostolimab coformulation, consisting of 200 mg of pembrolizumab + 200 mg vibostolimab, on Day 1 of each 21-day infusion cycle for up to 35 cycles. | Biological: pembrolizumab/vibostolimab coformulation<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684A;|
| Experimental: vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide<br>Participants 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. | Biological: vibostolimab<br>* Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684;Biological: pembrolizumab<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-3475;Drug: carboplatin<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4<br>* Other names: PARAPLATIN®;Drug: cisplatin<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4<br>* Other names: PLATINOL-AQ®;Drug: etoposide<br>* Administered as an IV infusion on Days 1-3 of 21-day infusion Cycles 1-4<br>* Other names: ETOPOPHOS®;|
| Experimental: pembrolizumab/vibostolimab coformulation China cohort<br>Participants from mainland China will receive a fixed dose of pembrolizumab/vibostolimab coformulation, consisting of 200 mg of pembrolizumab + 200 mg vibostolimab, on Day 1 of each 21-day infusion cycle for up to 35 cycles. | Biological: pembrolizumab/vibostolimab coformulation<br>* Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35<br>* Other names: MK-7684A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLTs) |  | Up to 24 Months | 
| Number of Participants Who Experienced At Least One Adverse Event (AE) |  | Up to 27 Months | 
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) |  | Up to 24 Months | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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