MK-7684A With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors (MK-7684A-005) (KEYVIBE-005)

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of pembrolizumab/vibostolimab co-formulation (MK-7684A) with or without other anticancer therapies in participants with selected advanced solid tumors. The primary hypothesis is that pembrolizumab/vibostolimab co-formulation is superior to pembrolizumab alone in terms of objective response rate or progression-free survival in participants with cervical cancer.

Official Title
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A Multicenter, Open-label, Phase 2 Basket Study of MK-7684A, a Co-formation of Vibostolimab (MK-7684) With Pembrolizumab (MK-3475), With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors

Conditions
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Uterine Cervical Neoplasms, Endometrial Neoplasms, Squamous Cell Carcinoma of Head and Neck, Gallbladder Neoplasms, Cholangiocarcinoma, Esophageal Neoplasms, Triple Negative Breast Neoplasms, Hepatocellular Carcinoma, Urinary Bladder Neoplasms, Ovarian Neoplasms, Stomach Neoplasms

Intervention / Treatment
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* Biological: Pembrolizumab/Vibostolimab Co-Formulation
* Biological: Pembrolizumab
* Drug: Lenvatinib
* Drug: 5-Fluorouracil
* Drug: Cisplatin
* Drug: Paclitaxel
* Drug: Gemcitabine
* Drug: Carboplatin
* Drug: Docetaxel
* Drug: Bevacizumab
* Drug: Capecitabine
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One of the following histologically or cytologically confirmed, advanced (unresectable or metastatic) solid tumors: Squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix Endometrial cancer Head and neck squamous cell carcinoma (HNSCC) Unresectable biliary adenocarcinoma (gallbladder or biliary tree [intrahepatic or extrahepatic] cholangiocarcinoma) Adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the gastroesophageal junction (GEJ). Triple-negative breast cancer (TNBC) Hepatocellular carcinoma (HCC) Urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra Ovarian cancer Gastric cancer Measurable disease per RECIST v1.1 as assessed by BICR or local site investigator. Adequately controlled blood pressure (BP) with or without antihypertensive medications. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART). Male participants must agree to follow contraceptive guidance. Female participants are not pregnant or breastfeeding, not a woman of child-bearing potential (WOCBP) or is a WOCBP and agrees to follow contraceptive guidance. Adequate organ function. Exclusion Criteria: History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years. Prior therapy with anti-programmed cell-death (PD-1), anti-PD-L1, anti-PD-L2, or anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) agent. Prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study medication. Active autoimmune disease that has required systemic treatment in past 2 years. Active infection requiring systemic therapy. Concurrent active hepatitis B and hepatitis C virus infection. History of allogenic tissue/solid organ transplant. Previous treatment with lenvatinib (for participants who will receive lenvatinib in their assigned treatment arm). Has clinically significant cardiovascular disease within 12 months from first dose of study intervention.

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants with locally recurrent unresectable or metastatic cervical cancer whose tumors express programmed cell death 1 ligand 1 (PD-LI) and have a combined positive score (CPS) ≥1 will be randomly assigned to treatment with either pembrolizumab/vibostolimab co-formulation or pembrolizumab only. The other study intervention arms will be assigned to participants depending on the selected cancer type.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab/Vibostolimab Co-Formulation<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion every 3 weeks (Q3W) up to 35 cycles. | Biological: Pembrolizumab/Vibostolimab Co-Formulation<br>* Pembrolizumab 200 mg plus vibostolimab 200 mg administered via IV infusion Q3W<br>* Other names: MK-7684A;|
| Experimental: Pembrolizumab<br>Participants receive pembrolizumab 200 mg via IV infusion Q3W up to 35 cycles. | Biological: Pembrolizumab<br>* Pembrolizumab 200 mg administered via IV infusion Q3W.<br>* Other names: KEYTRUDA®;|
| Experimental: Pembrolizumab/Vibostolimab Co-Formulation + Lenvatinib (Endometrial Cancer Cohort)<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion Q3W up to 35 cycles, plus lenvatinib 20 mg once daily (qd) until meeting discontinuation criteria. | Biological: Pembrolizumab/Vibostolimab Co-Formulation<br>* Pembrolizumab 200 mg plus vibostolimab 200 mg administered via IV infusion Q3W<br>* Other names: MK-7684A;Drug: Lenvatinib<br>* Lenvatinib 20 mg, 12 mg, or 8 mg (dependent on cancer type and body weight) administered via oral capsule QD<br>* Other names: MK-7902;|
| Experimental: Pembrolizumab/Vibostolimab Co-Formulation + Lenvatinib (Hepatocellular Cancer Cohort)<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion Q3W up to 35 cycles, plus lenvatinib 12 mg (body weight [BW] ≥60 kg) or lenvatinib 8 mg (BW <60 kg) qd until meeting discontinuation criteria. | Biological: Pembrolizumab/Vibostolimab Co-Formulation<br>* Pembrolizumab 200 mg plus vibostolimab 200 mg administered via IV infusion Q3W<br>* Other names: MK-7684A;Drug: Lenvatinib<br>* Lenvatinib 20 mg, 12 mg, or 8 mg (dependent on cancer type and body weight) administered via oral capsule QD<br>* Other names: MK-7902;|
| Experimental: Pembrolizumab/Vibostolimab + 5-Fluorouracil + Cisplatin<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion Q3W, plus 5-fluorouracil (5-FU), plus Cisplatin as background therapy. | Biological: Pembrolizumab/Vibostolimab Co-Formulation<br>* Pembrolizumab 200 mg plus vibostolimab 200 mg administered via IV infusion Q3W<br>* Other names: MK-7684A;Drug: 5-Fluorouracil<br>* 5-FU 800 mg/m^2/day administered via continuous IV infusion on each of days 1 to 5 Q3W for up to 35 cycles<br>* Other names: Fluracil;Drug: Cisplatin<br>* Cisplatin administered via IV infusion<br>* Other names: cis Platinum;|
| Experimental: Pembrolizumab/Vibostolimab Co-Formulation + Paclitaxel<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion Q3W up to 35 cycles, plus paclitaxel as background therapy until meeting discontinuation criteria. | Biological: Pembrolizumab/Vibostolimab Co-Formulation<br>* Pembrolizumab 200 mg plus vibostolimab 200 mg administered via IV infusion Q3W<br>* Other names: MK-7684A;Drug: Paclitaxel<br>* Paclitaxel administered via IV infusion at investigator's choice of dose<br>* Other names: Anzatax;|
| Experimental: Pembrolizumab/Vibostolimab Co-Formulation + Gemcitabine/Cisplatin<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion Q3W up to 35 cycles, plus gemcitabine (until disease progression or unacceptable toxicity) and cisplatin (up to 8 cycles) as background therapy. | Drug: Cisplatin<br>* Cisplatin administered via IV infusion<br>* Other names: cis Platinum;Drug: Gemcitabine<br>* Gemcitabine administered via IV infusion on Day 1 and Day 8 of each 3-week cycle, until PD or unacceptable toxicity<br>|
| Experimental: Pembrolizumab/Vibostolimab Co-Formulation+ Carboplatin/Paclitaxel/Bevacizumab<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion Q3W up to 35 cycles, plus carboplatin, paclitaxel, and bevacizumab as background therapy. | Drug: Paclitaxel<br>* Paclitaxel administered via IV infusion at investigator's choice of dose<br>* Other names: Anzatax;Drug: Carboplatin<br>* Carboplatin administered via IV infusion at investigator's choice of dose and frequency<br>Drug: Docetaxel<br>* For participants who cannot receive paclitaxel due to hypersensitivity or adverse event (AE), docetaxel administered via IV infusion Q3W, Day 1 of each cycle for up to 5 cycles<br>Drug: Bevacizumab<br>* Bevacizumab (or biosimilars such as MVASI®, Zirabev®, Aybintio®, ALYMSYS®, Abevmy®, Onbevezy®, Vegzelma®) administered via IV infusion Q3W; Day 1 of each 3-week cycle for up to 15 cycles<br>|
| Experimental: Pembrolizumab/Vibostolimab Co-Formulation + Capecitabine/Oxaliplatin<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion Q3W up to 35 cycles, plus capecitabine and oxaliplatin as background therapy. | Drug: Capecitabine<br>* Capecitabine administered via oral tablet twice daily on Days 1 to 14 of each cycle (Q3W) for up to 35 cycles<br>Drug: Oxaliplatin<br>* Oxaliplatin administered via IV infusion Q3W up to 35 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR) | ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented. | Up to approximately 2 years | 
| Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented. | Up to approximately 2 years | 
| ORR per RECIST 1.1 as Assessed by Investigator in Participants with Selected Solid Tumors | ORR is defined as the percentage of participants who have a CR (Disappearance of all target lesions) or a PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by investigator based on RECIST 1.1 will be presented. | Up to approximately 2 years | 
| PFS per RECIST 1.1 as Assessed by Investigator at 9 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. | 9 months | 
| PFS per RECIST 1.1 as Assessed by Investigator at 12 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to approximately 5.5 years | 
| PFS per RECIST 1.1 as Assessed by Investigator | PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by investigator will be presented. | Up to approximately 2 years | 
| Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR | For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by BICR will be presented. | Up to approximately 2 years | 
| DOR per RECIST 1.1 as Assessed by Investigator | For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by investigator will be presented. | Up to approximately 2 years | 
| ORR per RECIST 1.1 as Assessed by Investigator | ORR is defined as the percentage of participants who have a CR (Disappearance of all target lesions) or a PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by investigator based on RECIST 1.1 will be presented. | Up to approximately 2 years | 
| PFS per RECIST 1.1 as Assessed by Investigator in Participants with Cervical Cancer | PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by investigator will be presented. | Up to approximately 2 years | 
| Change from Baseline in Global Health Status/Quality of Life Score (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 [EORTC QLQ-C30] Items 29 and 30) | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? and How would you rate your overall quality of life during the past week? are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented. | Baseline and up to approximately 2 years | 
| Change from Baseline in Physical Functioning Score (EORTC QLQ-C30 Items 1-5) | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented. | Baseline and up to approximately 2 years | 
| Number of Participants Who Experienced One or More Adverse Events (AEs) | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. | Up to approximately 2 years | 
| Number of Participants Who Discontinued Study Intervention Due to an AE | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. | Up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)