ccRCCPhase 1NCT02293980
A Phase 1, Dose-Escalation Trial of PT2385 Tablets In Patients With Advanced Clear Cell Renal Cell Carcinoma (MK-3795-001)
A Phase 1 study testing MK-3795, Nivolumab and Cabozantinib in people with ccRCC and RCC, run by Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 25 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ccRCC, RCC, Kidney Cancer
- What is being tested?
- MK-3795, Nivolumab and Cabozantinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 25 sitesUnited States
- Study dates
- 25 Nov 2014to 30 Nov 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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 locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
Emory University Winship Cancer Institue
Atlanta, Georgia, 30322
University of Colorado Cancer Center
Aurora, Colorado, 80045
University of Maryland - Greenebaum Cancer Center
Baltimore, Maryland, 21201
Massachusetts General Hospital - Cancer Center
Boston, Massachusetts, 02114
Beth Israel Deconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Rush University Medical Center
Chicago, Illinois, 60612
Cleveland Clinic
Cleveland, Ohio, 44195
The Ohio State University
Columbus, Ohio, 43210
UT Southwestern Medical Center
Dallas, Texas, 75239
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
Virginia Cancer Specialists
Fairfax, Virginia, 22031
The West Clinic
Germantown, Tennessee, 38138
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Tennessee Oncology
Nashville, Tennessee, 37203
Vanderbilt Medical Center
Nashville, Tennessee, 37232
Yale School of Medicine
New Haven, Connecticut, 06510
Mount Sinai Heath System
New York, New York, 10019-1147
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of Pittsburg Medical Center
Pittsburgh, Pennsylvania, 15232
Swedish Cancer Institute
Seattle, Washington, 98104
University of Washington
Seattle, Washington, 98109
About this study
Official title: A Phase 1, Multiple-Dose, Dose-Escalation Trial of PT2385 Tablets, a HIF-2α Inhibitor, in Patients With Advanced Clear Cell Renal Cell Carcinoma
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.
Read the detailed 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.
- Conditions
- ccRCC, RCC, Kidney Cancer, Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma
- Being tested
- MK-3795, Nivolumab, Cabozantinib, Bezlutifan
- Medical subject headings
- Kidney Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-3795Drug
Also called PT2385, PT-2385, HIF-2a, MK-3795
Oral administration
NivolumabDrug
Also called Opdivo
IV infusion
CabozantinibDrug
Also called Cabometyx
Oral administration
BezlutifanDrug
Also called MK-6482
Oral administration
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: MK-3795; Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Part 1: 3 Weeks; Part 2: 4 Weeks, Part 3: 4 Weeks
Secondary outcomes (25)
Number of Participants Who Experience an Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of participants who experience an AE will be presented.
Measured: Up to approximately 9 years
Best Response (BOR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
BOR is the best tumor response recorded up until documentation of progression of disease (PD) or death from any cause, or until the patient withdraws consent. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.
Measured: Up to approximately 1 year
Objective Response Rate (ORR) per RECIST 1.1
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR based on RECIST 1.1 will be presented.
Measured: Up to approximately 1 year
Progression-Free Survival (PFS) per RECIST 1.1
PFS is defined as the time from the first dose of MK-3795 to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.
Measured: Up to approximately 9 years
Duration of Response (DOR) per RECIST 1.1
For participants who demonstrate a confirmed Complete Response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The median DOR will be presented.
Measured: Up to approximately 1 year
Clinical Benefit Rate (CBR) per RECIST 1.1
CBR is defined as the percentage of participants who achieve clinical benefit. Clinical benefit is defined as a best response of CR (Disappearance of all target lesions), PR (At least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.]).
Measured: Up to approximately 1 year
Maximum concentration (Cmax) of Study Treatment
Blood samples will be collected at designated timepoints for the determination of Cmax. Cmax was defined as the maximum concentration of study treatment is reached.
Measured: At designated timepoints (up to 106 days)
Time to Maximum Concentration (Tmax) of Study Treatment
Blood samples will be collected at designated timepoints the determination of Tmax. Tmax is defined as the time to the maximum concentration of study treatment reached.
Measured: At designated timepoints (up to 106 days)
Terminal half-life (t½λz) of Study Treatment
Blood samples will be collected at designated timepoints for the determination of (t½λz). (t½λz) is defined as the time required for the plasma concentration of study drug to decrease 50% in the final stage of its elimination.
Measured: At designated timepoints (up to 106 days)
Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) of Study Treatment
Blood samples will be collected at designated timepoints for the determination of AUC0-inf. AUC0-inf is the area under the serum concentration-time curve from time zero to infinity.
Measured: At designated timepoints (up to 106 days)
Area Under the Concentration-Time Curve From 0 to Inf Extrapolated (AUC0-inf Extrap) of Study Treatment
Blood samples were collected at designated timepoints for the determination of AUC0-inf extrapolated. AUC0-inf extrapolated is a measure of mean concentration in serum from time zero to infinity.
Measured: At designated timepoints (up to 106 days)
Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Study Treatment
Blood samples were collected at designated timepoints for the determination of AUC0-12. AUC0-12 is a measure of mean concentration in serum from time zero to 12 hours.
Measured: At designated timepoints (up to 106 days)
Area Under the Plasma Concentration-time Curve From Time 0 to Last (AUC0-last) of Study Treatment
Blood samples were collected at designated timepoints for the determination of AUC0-last. AUC0-last is a measure of mean concentration in serum from time zero to last measurable concentration.
Measured: At designated timepoints (up to 106 days)
Apparent Volume of Distribution (Vz/F) of Study Treatment
Blood samples were collected at designated timepoints for the determination of Vz/F. Vz/F is a the volume of study drug that would need to be uniformly distributed to produce desired serum concentration. F is the fraction of the dose absorbed.
Measured: At designated timepoints (up to 106 days)
Apparent Clearance (CL/F) of Study Treatment
Blood samples were collected at designated timepoints for the determination of CL/F. CL/F is a the volume of plasma from which study drug was eliminated per unit time. F is the fraction of the dose absorbed.
Measured: At designated timepoints (up to 106 days)
Accumulation Ratio (RAC)
Blood samples were collected at designated timepoints for the determination of RAC. RAC is calculated as AUC0-12 at steady state divided by AUC0-12 after first dose.
Measured: At designated timepoints (up to 106 days)
Mean Plasma Concentration of Erythropoietin (EPO) Level
Blood samples will be collected at designated timepoints to measure EPO level. The mean concentration of EPO level will be reported.
Measured: At designated timepoints (up to 106 days)
Mean Plasma Concentration of Plasminogen Activator Inhibitor 1 (PAI-1) Level
Blood samples will be collected at designated timepoints to measure PAI-1 level. The mean concentration of PAI-1 level will be reported.
Measured: At designated timepoints (up to 106 days)
Mean Plasma Concentration of Insulin Growth Factor Binding Protein 3 (IGFBP3) Level
Blood samples will be collected at designated timepoints to measure IGFBP3 level. The mean concentration of IGFBP3 level will be reported.
Measured: At designated timepoints (up to 106 days)
Mean Plasma Concentration of Vascular Endothelial Growth Factor A (VEGFa) Level
Blood samples will be collected at designated timepoints to measure VEGFa level. The mean concentration of VEGFa level will be reported.
Measured: At designated timepoints (up to 106 days)
Percent Change from Baseline in the EPO Level
Blood samples will be collected at designated timepoints to measure EPO level. The percent change from baseline in EPO level up to approximately Week 16 will be reported.
Measured: Baseline and up to approximately Week 16
Percent Change from Baseline in the PAI-1 Level
Blood samples will be collected at designated timepoints to measure PAI-1 level. The percent change from baseline in PAI-1 level up to approximately Week 16 will be reported.
Measured: Baseline and up to approximately Week 16
Percent Change from Baseline in the IGFBP3 Level
Blood samples will be collected at designated timepoints to measure IGFBP3 level. The percent change from baseline in IGFBP3 level up to approximately Week 16 will be reported.
Measured: Baseline and up to approximately Week 16
Percent Change from Baseline in the VEGFa
Blood samples will be collected at designated timepoints to measure VEGFa level. The percent change from baseline in VEGFa level up to approximately Week 16 will be reported.
Measured: Baseline and up to approximately Week 16
Antitumor Activity
Antitumor activity will be assessed by non-contrast or contrast computerized tomography (CT) or magnetic resonance imaging (MRI) at baseline, during Week 6, and every 9 weeks thereafter up to approximately 1 year.
Measured: Baseline, at Week 6 and every 9 Weeks thereafter up to approximately 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2014 (estimated)
- Study start25 Nov 2014
- Primary completion31 Jan 2017
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ccRCCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02293980
- Sponsor's protocol ID
- 3795-001
- Other IDs
- PT2385-101, MK-3795-001
- Status last verified
- May 2024
- First submitted
- 14 Nov 2014
- Last updated
- 17 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
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.
PubMed 29257710
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multiple-Dose, Dose-Escalation Trial of PT2385 Tablets, a HIF-2α Inhibitor, in Patients With Advanced Clear Cell Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02293980
- Acronym / sponsor ID
- 3795-001
- Conditions
- ccRCC, RCC, Kidney Cancer, Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 25 Nov 2014 (actual)
- Primary completion
- 31 Jan 2017 (actual)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 19 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: MK-3795 | Experimental | Drug: MK-3795Participants 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. |
| Part 2: MK-3795 + Nivolumab + Belzutifan | Experimental | Drug: MK-3795, Drug: Nivolumab, Drug: BezlutifanParticipants 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. |
| Part 3: MK-3795 + Cabozantinib | Experimental | Drug: MK-3795, Drug: CabozantinibParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-3795Also: PT2385, PT-2385, HIF-2a, MK-3795Oral administration | Drug | Part 1: MK-3795, Part 2: MK-3795 + Nivolumab + Belzutifan, Part 3: MK-3795 + Cabozantinib |
| NivolumabAlso: OpdivoIV infusion | Drug | Part 2: MK-3795 + Nivolumab + Belzutifan |
| CabozantinibAlso: CabometyxOral administration | Drug | Part 3: MK-3795 + Cabozantinib |
| BezlutifanAlso: MK-6482Oral administration | Drug | Part 2: MK-3795 + Nivolumab + Belzutifan |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Part 1: 3 Weeks, Part 2: 4 Weeks, Part 3: 4 Weeks
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.
Recommended Phase 2 Dose (RP2D)
Time frame: Part 1: 3 Weeks; Part 2: 4 Weeks, Part 3: 4 Weeks
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.
25 secondary outcomes
Number of Participants Who Experience an Adverse Event (AE)
Time frame: Up to approximately 9 years
Best Response (BOR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: Up to approximately 1 year
Objective Response Rate (ORR) per RECIST 1.1
Time frame: Up to approximately 1 year
Progression-Free Survival (PFS) per RECIST 1.1
Time frame: Up to approximately 9 years
Duration of Response (DOR) per RECIST 1.1
Time frame: Up to approximately 1 year
Clinical Benefit Rate (CBR) per RECIST 1.1
Time frame: Up to approximately 1 year
Maximum concentration (Cmax) of Study Treatment
Time frame: At designated timepoints (up to 106 days)
Time to Maximum Concentration (Tmax) of Study Treatment
Time frame: At designated timepoints (up to 106 days)
Terminal half-life (t½λz) of Study Treatment
Time frame: At designated timepoints (up to 106 days)
Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) of Study Treatment
Time frame: At designated timepoints (up to 106 days)
Area Under the Concentration-Time Curve From 0 to Inf Extrapolated (AUC0-inf Extrap) of Study Treatment
Time frame: At designated timepoints (up to 106 days)
Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of Study Treatment
Time frame: At designated timepoints (up to 106 days)
Area Under the Plasma Concentration-time Curve From Time 0 to Last (AUC0-last) of Study Treatment
Time frame: At designated timepoints (up to 106 days)
Apparent Volume of Distribution (Vz/F) of Study Treatment
Time frame: At designated timepoints (up to 106 days)
Apparent Clearance (CL/F) of Study Treatment
Time frame: At designated timepoints (up to 106 days)
Accumulation Ratio (RAC)
Time frame: At designated timepoints (up to 106 days)
Mean Plasma Concentration of Erythropoietin (EPO) Level
Time frame: At designated timepoints (up to 106 days)
Mean Plasma Concentration of Plasminogen Activator Inhibitor 1 (PAI-1) Level
Time frame: At designated timepoints (up to 106 days)
Mean Plasma Concentration of Insulin Growth Factor Binding Protein 3 (IGFBP3) Level
Time frame: At designated timepoints (up to 106 days)
Mean Plasma Concentration of Vascular Endothelial Growth Factor A (VEGFa) Level
Time frame: At designated timepoints (up to 106 days)
Percent Change from Baseline in the EPO Level
Time frame: Baseline and up to approximately Week 16
Percent Change from Baseline in the PAI-1 Level
Time frame: Baseline and up to approximately Week 16
Percent Change from Baseline in the IGFBP3 Level
Time frame: Baseline and up to approximately Week 16
Percent Change from Baseline in the VEGFa
Time frame: Baseline and up to approximately Week 16
Antitumor Activity
Time frame: Baseline, at Week 6 and every 9 Weeks thereafter up to approximately 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2024.
- Derived from this study: PubMed 29257710Courtney 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.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Related trials for ccRCC
Active, not recruitingPhase 3
A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)
Carcinoma, Renal Cell
RecruitingPhase 1
Open-Label Phase 1/2 Study of NEO-811 in Subjects With Locally Advanced or Metastatic Non-Resectable Clear Cell Renal Cell Carcinoma
Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma
RecruitingPhase 1/2
A Trial to Find Out if REGN5678 (Nezastomig) is Safe and How Well it Works Alone or in Combination With Cemiplimab for Adult Participants With Metastatic Castration-Resistant Prostate Cancer and Other Tumors
Metastatic Castration-Resistant Prostate Cancer (mCRPC), Clear Cell Renal Cell Carcinoma (ccRCC)
RecruitingPhase 3
Study of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma
Metastatic Clear Cell Renal Cell Carcinoma, Advanced Clear Cell Renal Cell Carcinoma
Active, not recruitingPhase 1/2
AB-2100, an Integrated Circuit T Cell Therapy in Patients With Recurrent Clear-cell Renal Cell Carcinoma (ccRCC)
Advanced/Metastatic Clear Cell Renal Cell Carcinoma, Recurrence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-3795, Nivolumab and Cabozantinib in people with ccRCC and RCC, run by Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Part 1: 3 Weeks, Part 2: 4 Weeks, Part 3: 4 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02293980, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2024.