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

NCT02293980 | Active Not Recruiting Phase 1

• 3 other identifiers: 3795-001PT2385-101MK-3795-001
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 25

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  MTD of MK-3795 will be determined. MTD will be defined as the dose level at which 2 or more participants experience a dose limiting toxicity (DLT) which will be deemed intolerable and the dose level below will be declared the MTD.

  Part 1: 3 Weeks, Part 2: 4 Weeks, Part 3: 4 Weeks

• Recommended Phase 2 Dose (RP2D)

  The RP2D of MK-3795 will be determined. The RP2D will be determined based on the MTD (or the optimal biological dose (OBD) if the MTD is not identified), the overall safety profile with continued treatment, and pharmacokinetic (PK) profile.

  Part 1: 3 Weeks; Part 2: 4 Weeks, Part 3: 4 Weeks

Secondary Outcomes (25)

• Number of Participants Who Experience an Adverse Event (AE)

  Up to approximately 9 years

• Best Response (BOR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 1 year

• Objective Response Rate (ORR) per RECIST 1.1

  Up to approximately 1 year

• Progression-Free Survival (PFS) per RECIST 1.1

  Up to approximately 9 years

• Duration of Response (DOR) per RECIST 1.1

  Up to approximately 1 year

Study Arms (3)

Part 1: MK-3795

EXPERIMENTAL

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.

Drug: MK-3795

Part 2: MK-3795 + Nivolumab + Belzutifan

EXPERIMENTAL

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.

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

Part 3: MK-3795 + Cabozantinib

EXPERIMENTAL

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.

Drug: MK-3795; Drug: Cabozantinib

Interventions

MK-3795 DRUG

Oral administration

Also known as: PT2385, PT-2385, HIF-2a, MK-3795

Part 1: MK-3795; Part 2: MK-3795 + Nivolumab + Belzutifan; Part 3: MK-3795 + Cabozantinib

Nivolumab DRUG

IV infusion

Also known as: Opdivo

Part 2: MK-3795 + Nivolumab + Belzutifan

Cabozantinib DRUG

Oral administration

Also known as: Cabometyx

Part 3: MK-3795 + Cabozantinib

Bezlutifan DRUG

Oral administration

Also known as: MK-6482

Part 2: MK-3795 + Nivolumab + Belzutifan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (25)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Emory University Winship Cancer Institue

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Maryland - Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital - Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mount Sinai Heath System

New York, New York, 10019-1147, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

The West Clinic

Germantown, Tennessee, 38138, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75239, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 29257710 DERIVED

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

PT2385; endothelial PAS domain-containing protein 1; Nivolumab; cabozantinib; belzutifan

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2014
• First Posted: November 19, 2014
• Study Start: November 25, 2014
• Primary Completion: January 31, 2017
• Study Completion (Estimated): November 30, 2026
• Last Updated: June 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

US (25)