Recruiting
Phase 1
Phase 2

PC14586

Sponsor:

PMV Pharmaceuticals, Inc

Code:

NCT04585750

Conditions

Advanced Solid Tumor

Advanced Malignant Neoplasm

Metastatic Cancer

Metastatic Solid Tumor

Lung Cancer

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Interventions

rezatapopt

pembrolizumab

Study Details

Brief summary:

The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. The Phase 1 portion of the study will assess the safety, tolerability and preliminary efficacy of multiple dose levels of rezatapopt as monotherapy and in Phase 1b in combination with pembrolizumab.

Conditions

Advanced Solid Tumor

Advanced Malignant Neoplasm

Metastatic Cancer

Metastatic Solid Tumor

Lung Cancer

Study ID

NCT04585750

Start date

Oct 29, 2020

Status verified date

Mar, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Aug 15, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • At least 18 years of age or 12 to 17 years of age after Safety Review Committee approval.
  • Locally advanced or metastatic solid malignancy with a TP53 Y220C mutation
  • Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
  • Previously treated with one or more lines of anticancer therapy and progressive disease
  • Adequate organ function
  • Measurable disease per RECIST v1.1 (Phase 2)

Additional Criteria for Inclusion in Phase 1b (rezatapopt) + pembrolizumab combination)

  • Anti-PD-1/PD-L1 naive or must have progressed on treatment
  • Measurable disease

Exclusion Criteria:

  • Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug
  • Radiotherapy within 14 days of receiving the study drug
  • Primary CNS tumor
  • History of leptomeningeal disease or spinal cord compression
  • Brain metastases, unless neurologically stable and do not require steroids to treat associated neurological symptoms
  • Stroke or transient ischemic attack within 6 months prior to screening
  • Heart conditions such as unstable angina within 6 months prior to screening, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities
  • Strong CYP3A4 inducers and strong CYP2C9 inhibitors/inducers within 14 days of first dose of rezatapopt
  • History of gastrointestinal (GI) disease that may interfere with absorption of study drug or patients unable to take oral medication
  • History of prior organ transplant
  • Known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer
  • Known, active uncontrolled Hepatitis B, Hepatitis C, or human immunodeficiency virus infection

Additional Criteria for Exclusion from Phase 2 (rezatapopt monotherapy)

  • Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2)

Additional Criteria for Exclusion from Phase 1b (rezatapopt) + pembrolizumab combination)

  • Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and discontinued from that treatment due to a Grade 3 or higher immune-related AE (irAE)
  • Received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention
  • Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy within 7 days prior to the first dose of study drug
  • Hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • History of radiation pneumonitis
  • History of (non-infectious) or active pneumonitis / interstitial lung disease that required steroids
  • Active infection requiring systemic therapy
  • Known history of HIV infection
  • Has previously received rezatapopt

Study Design

Enrollment

300 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1 Monotherapy Dose Escalation

Multiple dose levels of daily oral rezatapopt will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of rezatapopt to recommend a Phase 2 dose (RP2D).

experimental: Phase 1b Combination Therapy Dose Escalation, Part 1

Multiple dose levels of daily oral rezatapopt in combination with a stable dose of pembrolizumab (200 mg IV q3 weeks) will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of PC14586 to recommend a Phase 2 dose (RP2D) of rezatapopt when administered in combination with pembrolizumab.

experimental: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patients

Additional (expansion of) participants will enroll at the RP2D of daily oral PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 naive patients.

experimental: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patients

Additional (expansion of) participants will enroll at the RP2D of daily oral rezatapopt when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 relapsed/refractory patients.

experimental: Phase 2 Monotherapy Dose Expansion, Ovarian Cancer Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Ovarian Cancer Cohort participants will have locally advanced or metastatic ovarian cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.

experimental: Phase 2 Monotherapy Dose Expansion, Lung Cancer Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Lung Cancer Cohort participants will have locally advanced or metastatic lung cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.

experimental: Phase 2 Monotherapy Dose Expansion, Breast Cancer Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Breast Cancer Cohort participants will have locally advanced or metastatic breast cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.

experimental: Phase 2 Monotherapy Dose Expansion, Endometrial Cancer Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Endometrial Cancer Cohort participants will have locally advanced or metastatic endometrial cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.

experimental: Phase 2 Monotherapy Dose Expansion, Other Solid Tumors Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Other Solid Tumors Cohort participants will have locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.

Interventions

rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

pembrolizumab

Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.

Primary outcome measure

  • Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt [ Time Frame: 40 months ]
  • Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) [ Time Frame: 30 months ]
  • Phase 1 Monotherapy (Dose Escalation): Establish the maximum tolerated dose (MTD) (Phase 1) [ Time Frame: The first 28 days of treatment (Cycle 1) per patient ]
  • Phase 1b Combination Therapy (Part 1: Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab [ Time Frame: 18 months for treatment arm ]
  • Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the maximum tolerated dose (MTD) of rezatapopt when administered in combination with pembrolizumab [ Time Frame: The first 28 days of combination treatment arm (starting on Day -7) per patient ]
  • Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) of rezatapopt when administered in combination with pembrolizumab [ Time Frame: 18 months ]
  • Phase 1b Combination Therapy (Part 2: Dose Expansion): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab [ Time Frame: 12 months for treatment arm ]
  • Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt [ Time Frame: 34 months ]
  • Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt in ovarian cancer patients [ Time Frame: 34 months ]

Central Contacts and Locations

Central contacts

PMV Pharma Clinical Study Information Center

(609) 235-4038clinicaltrials@pmvpharma.com

Locations

University of San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92093

UCLA Jonsson Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90024

USC Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Rocky Mountain Cancer Center

Recruiting

Denver, Colorado, United States, 80218

Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06519

Medical Oncology Hematology Consultants

Recruiting

Newark, Delaware, United States, 19713

University of Miami - Sylvester Comprehensive Cancer Center

Recruiting

Miami, Florida, United States, 33136

Advent Health

Recruiting

Orlando, Florida, United States, 32803

Florida Cancer Specialists South

Recruiting

Port Charlotte, Florida, United States, 33980

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Karmanos Cancer Institute

Recruiting

Detroit, Michigan, United States, 48201

Memorial Sloan Kettering

Recruiting

New York, New York, United States, 10065

Duke University

Recruiting

Durham, North Carolina, United States, 27705

The Cleveland Clinic Taussig Cancer Center

Recruiting

Cleveland, Ohio, United States, 44195

University of Oklahoma

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Oregon Health & Science University (OHSU)

Recruiting

Portland, Oregon, United States, 97210

Abramson Cancer Center of the University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

WellSpan York Cancer Center

Recruiting

York, Pennsylvania, United States, 17403

Sarah Cannon Research Institute

Recruiting

Nashville, Tennessee, United States, 37203

New Experimental Therapeutics - NEXT Oncology

Recruiting

Austin, Texas, United States, 78705

Texas Oncology

Recruiting

Bedford, Texas, United States, 76022

UT Southwest Simmons Cancer Center

Recruiting

Dallas, Texas, United States, 75390

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

New Experimental Therapeutics of San Antonio - NEXT Oncology

Recruiting

San Antonio, Texas, United States, 78229

Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

University of Washington, Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

University of Wisconsin Carbone Cancer Center

Recruiting

Madison, Wisconsin, United States, 53705

More Information

Sponsor

PMV Pharmaceuticals, Inc

Last update posted

Aug 10, 2026

Last verified

Mar, 2026

Keywords

  • PC14586
  • p53
  • Y220C
  • Phase 1
  • Phase 1/2
  • PMV
  • PMV Pharma
  • p53 mutation
  • TP53
  • TP53 mutation
  • p53 mutant
  • p53 reactivator
  • pembrolizumab
  • Keytruda
  • combination
  • PD-1
  • PD-L1
  • anti-PD-1
  • Merck
  • MSD
  • IgG4
  • mAb
  • Phase 1b
  • NGS
  • Next Generation Sequencing
  • precision
  • Phase 2
  • Rezatapopt

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by PMV Pharmaceuticals, Inc on 2026-08-10.