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

NCT ID: NCT02293980

Last Updated: 2024-06-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-25

Study Completion Date

2026-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

ccRCC RCC Kidney Cancer Clear Cell Renal Cell Carcinoma Renal Cell Carcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Part 1: MK-3795

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.

Group Type EXPERIMENTAL

MK-3795

Intervention Type DRUG

Oral administration

Part 2: MK-3795 + Nivolumab + Belzutifan

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.

Group Type EXPERIMENTAL

MK-3795

Intervention Type DRUG

Oral administration

Nivolumab

Intervention Type DRUG

IV infusion

Bezlutifan

Intervention Type DRUG

Oral administration

Part 3: MK-3795 + Cabozantinib

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.

Group Type EXPERIMENTAL

MK-3795

Intervention Type DRUG

Oral administration

Cabozantinib

Intervention Type DRUG

Oral administration

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

MK-3795

Oral administration

Intervention Type DRUG

Nivolumab

IV infusion

Intervention Type DRUG

Cabozantinib

Oral administration

Intervention Type DRUG

Bezlutifan

Oral administration

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

PT2385, PT-2385, HIF-2a, MK-3795 Opdivo Cabometyx MK-6482

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status

Yale School of Medicine

New Haven, Connecticut, United States

Site Status

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Emory University Winship Cancer Institue

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Maryland - Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital - Cancer Center

Boston, Massachusetts, United States

Site Status

Beth Israel Deconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Mount Sinai Heath System

New York, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

The West Clinic

Germantown, Tennessee, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Vanderbilt Medical Center

Nashville, Tennessee, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Courtney KD, Infante JR, Lam ET, Figlin RA, Rini BI, Brugarolas J, Zojwalla NJ, Lowe AM, Wang K, Wallace EM, Josey JA, Choueiri TK. Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2alpha Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma. J Clin Oncol. 2018 Mar 20;36(9):867-874. doi: 10.1200/JCO.2017.74.2627. Epub 2017 Dec 19.

Reference Type DERIVED
PMID: 29257710 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

PT2385-101

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3795-001

Identifier Type: OTHER

Identifier Source: secondary_id

3795-001

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Study of Durvalumab and Guadecitabine in Advanced Kidney Cancer
NCT03308396 ACTIVE_NOT_RECRUITING PHASE1/PHASE2