Title
A Phase 1, Dose-Escalation Trial of PT2385 Tablets In Patients With Advanced Clear Cell Renal Cell Carcinoma (MK-3795-001)
A Phase 1, Multiple-Dose, Dose-Escalation Trial of PT2385 Tablets, a HIF-2α Inhibitor, in Patients With Advanced Clear Cell Renal Cell Carcinoma
Phase
Phase 1Lead Sponsor
Peloton Therapeutics, Inc.Study Type
InterventionalStatus
Active, not recruitingIndication/Condition
ccRCC RCC Kidney Cancer ...Intervention/Treatment
nivolumab pt2385 cabozantinib ...Study Participants
110PART 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.
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.
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.
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.
Oral administration
IV infusion
Oral administration
Participants with advanced ccRCC receive MK-3475 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-3475. 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.
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 approximately 1 year (12 cycles; each cycle length = 28 days) or until unequivocal progression or treatment discontinuation, whichever occurs later.
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.
Inclusion Criteria PART 1 Has locally advanced or metastatic ccRCC and has progressed during treatment with at least one prior therapeutic regimen Is of age ≥ 18 years Has a life expectancy of ≥ 3 months Has adequate organ function If a female patient, must be surgically sterile, post-menopausal, or must agree to use physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration, or if a male patient with a female partner, must agree to use physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration 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 HIV 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 Gastrointestinal (GI) disorders Any history of congenital long QT syndrome
