A Phase 1, Dose-Escalation Trial of PT2385 Tablets In Patients With Advanced Clear Cell Renal Cell Carcinoma (MK-3795-001)

Peloton Therapeutics

Status and phase: Active, not recruiting; Phase 1

Conditions: Kidney Cancer; RCC; Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; ccRCC

Treatments: Drug: MK-3795; Drug: Nivolumab; Drug: Cabozantinib; Drug: Bezlutifan

Study type: Interventional

Funder types: Industry

Identifiers

NCT02293980

MK-3795-001 (Other Identifier)

3795-001

PT2385-101 (Other Identifier)

Details and patient eligibility

About

PART 1: The primary objective of this study is to identify the maximum tolerated dose (MTD) of MK-3795, formerly called PT2385 and/or the recommended Phase 2 dose (RP2D) of MK-3795 in patients with advanced clear cell renal cell carcinoma (ccRCC).

PART 2: The primary objective of this study is to identify the MTD of MK-3795 up to the RP2D, in combination with nivolumab, in patients with advanced ccRCC.As of Amendment 09 (29 Mar 2024), participants with advanced ccRCC will transition from MK-3795 to belzutifan (MK-6482) in combination with nivolumab or belzutifan alone.

PART 3: The primary objective of this study is to identify the MTD of MK-3795 up to the RP2D, in combination with cabozantinib tablets, in patients with advanced ccRCC.

Full description

PART 1: This is a Phase 1, multiple-dose, dose-escalation trial of MK-3795, where patients with advanced ccRCC will be assigned to sequential dose cohorts. Patient safety will be monitored with frequent physical examinations, vital sign measurements, electrocardiograms (ECGs), and hematology and chemistry laboratory studies, and by recording all adverse events (AEs). Blood will be obtained for analysis of the concentration of MK-3795 and to assess biomarkers.

PART 2: This is a Phase 1 trial of MK-3795 in combination with nivolumab, where patients with advanced ccRCC will be assigned to dose cohorts. Patient safety will be monitored with frequent physical examinations, vital sign measurements, ECGs, and hematology and chemistry laboratory studies, and by recording all AEs. Blood will be obtained for analysis of the concentration of MK-3795 and to assess biomarkers. As of Amendment 09 (29 Mar 2024), participants with advanced ccRCC will transition from MK-3795 to belzutifan in combination with nivolumab or belzutifan alone.

PART 3: This is a Phase 1 trial of MK-3795 in combination with cabozantinib tablets, where patients with advanced ccRCC will be assigned to dose cohorts. Patient safety will be monitored with frequent physical examinations, vital sign measurements, ECGs, and hematology and chemistry laboratory studies, and by recording all AEs. Blood will be obtained for analysis of the concentration of MK-3795 and cabozantinb and to assess biomarkers.

Enrollment: 110 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

PART 1

• Has locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) and has progressed during treatment with at least one prior therapeutic regimen
• Has a life expectancy of ≥ 3 months
• Has adequate organ function
• Able to swallow oral medications

PART 2 - In addition to PART 1

• Received no more than three prior systemic treatment regimens in the advanced or metastatic setting
• Must have received at least one but not more than two prior anti-angiogenic therapy regimens

PART 3 - In addition to PART 1

• Must have received at least one vascular endothelial growth factor receptor (VEGFR) targeting tyrosine kinase inhibitor

Exclusion Criteria

PART 1

• Has a history of untreated brain metastasis or history of leptomeningeal disease or spinal cord compression
• Has failed to recover from the reversible effects of prior anticancer therapy
• Has uncontrolled or poorly controlled hypertension
• Is receiving warfarin anticoagulant therapy or expected to require warfarin
• Has had any major cardiovascular event within 6 months prior to study drug administration
• Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results
• Has had major surgery within 4 weeks before first study drug administration
• Has known human immunodeficiency virus (HIV) infection
• Has an active infection requiring systemic treatment
• Is participating in another therapeutic clinical trial

PART 2 - In addition to PART 1

• Has received prior immunotherapy
• Has any active or recent history of a known or suspected autoimmune disease

PART 3 - In addition to PART 1

• Has gastrointestinal (GI) disorders
• Has any history of congenital long QT syndrome

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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110 participants in 3 patient groups

Part 1: MK-3795

Experimental group

Description:

Participants with advanced ccRCC receive MK-3795 at an initial dose level of 100mg orally, twice daily (BID) up to approximately 3 weeks. Dose levels will be escalated to identify the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) for MK-3795. Each escalated dose will be continued for up to approximately 3 weeks before escalating a dose again until a dose limiting toxicity (DLT) is experienced. Thereafter, participants receive RP2D dose of MK-3795 for up to 2 cycles (each cycle length = 28 days) for up to approximately 1 year. Participants may continue to receive MK-3795 beyond 1 year at the discretion of the Sponsor.

Treatment:

Drug: MK-3795

Part 2: MK-3795 + Nivolumab + Belzutifan

Experimental group

Description:

Participants with advanced ccRCC in the expansion phase receive the RP2D of MK-3795 orally in combination with nivolumab 240mg by IV infusion over \~60 minutes every 2 weeks for up to \~1 year (12 cycles; each cycle length = 28 days) or until unequivocal progression or treatment discontinuation, whichever occurs later. As per Amendment 09 (29 March 2024), participants will not receive MK-3795. Participants receive nivolumab 240mg by IV infusion over \~60 minutes every 2 weeks in combination with belzutifan 120 mg once daily (QD) for up to \~1 year (12 cycles; each cycle length = 28 days) or until unequivocal progression or treatment discontinuation, whichever occurs later. If participants experience an adverse event, then nivolumab will be discontinued and participants will continue to receive belzutifan 120 mg QD alone for up to \~1 year (12 cycles; each cycle length = 28 days) or until unequivocal progression or treatment discontinuation, whichever occurs later.

Treatment:

Drug: Bezlutifan

Drug: Nivolumab

Drug: MK-3795

Part 3: MK-3795 + Cabozantinib

Experimental group

Description:

Participants with advanced ccRCC in the expansion phase receive the RP2D of MK-3795 in combination with cabozantinib 20mg up to 60mg orally QD for up to approximately 1 year (12 cycles; each cycle length = 28 days) or until unequivocal progression or treatment discontinuation, whichever occurs later.

Treatment:

Drug: Cabozantinib

Drug: MK-3795