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

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 2

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05007106

MK-7684A-005 (Other Identifier)

KEYVIBE-005 (Other Identifier)

2021-001009-56 (EudraCT Number)

2023-505284-36 (Other Identifier)

7684A-005

jRCT2031210335 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 604 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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604 participants in 9 patient groups

Pembrolizumab/Vibostolimab Co-Formulation

Experimental group

Description:

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.

Treatment:

Biological: Pembrolizumab/Vibostolimab Co-Formulation

Pembrolizumab

Experimental group

Description:

Participants receive pembrolizumab 200 mg via IV infusion Q3W up to 35 cycles.

Treatment:

Biological: Pembrolizumab

Pembrolizumab/Vibostolimab Co-Formulation + Lenvatinib (Endometrial Cancer Cohort)

Experimental group

Description:

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) up to 45 cycles.

Treatment:

Drug: Lenvatinib

Biological: Pembrolizumab/Vibostolimab Co-Formulation

Pembrolizumab/Vibostolimab Co-Formulation + Lenvatinib (Hepatocellular Cancer Cohort)

Experimental group

Description:

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 up to 45 cycles

Treatment:

Drug: Lenvatinib

Biological: Pembrolizumab/Vibostolimab Co-Formulation

Pembrolizumab/Vibostolimab + 5-Fluorouracil + Cisplatin

Experimental group

Description:

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.

Treatment:

Drug: Cisplatin

Drug: 5-Fluorouracil

Biological: Pembrolizumab/Vibostolimab Co-Formulation

Pembrolizumab/Vibostolimab Co-Formulation + Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Biological: Pembrolizumab/Vibostolimab Co-Formulation

Pembrolizumab/Vibostolimab Co-Formulation + Gemcitabine/Cisplatin

Experimental group

Description:

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.

Treatment:

Drug: Cisplatin

Drug: Gemcitabine

Pembrolizumab/Vibostolimab Co-Formulation+ Carboplatin/Paclitaxel/Bevacizumab

Experimental group

Description:

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 local standard of care (SOC) background therapy.

Treatment:

Drug: Bevacizumab

Drug: Paclitaxel

Drug: Carboplatin

Drug: Docetaxel

Pembrolizumab/Vibostolimab Co-Formulation + Capecitabine/Oxaliplatin

Experimental group

Description:

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.

Treatment:

Drug: Capecitabine

Drug: Oxaliplatin