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Clinical Trials in France / NCT04585750
Recruiting Phase 1/2

The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

NCT04585750 · tracked via the Priya Life Science France tracker
Sponsor
PMV Pharmaceuticals, Inc
Phase
Phase 1/2
Started
2020-10-29
Last updated
2026-10-02

Condition(s) studied

Advanced Solid TumorAdvanced Malignant NeoplasmMetastatic CancerMetastatic Solid TumorLung CancerOvarian CancerEndometrial CancerProstate CancerColorectal CancerBreast CancerOther CancerLocally AdvancedHead and Neck CancerGall Bladder CancerSmall Cell Lung CancerSmall Cell Lung Cancer ( SCLC )Small Cell Lung CarcinomaNSCLCNSCLC (Non-small Cell Lung Cancer)SCLCNon-Small Cell Lung CarcinomaTriple Negative Breast CancerTNBCHER2+ Breast CancerNon-Small Cell Lung CancerER/PR Positive Breast CancerHER2- Breast CancerHER2-positive Breast CancerHER2-negative Breast CancerER/PR(+), Her2(-) Breast Cancer

Investigational drug(s) / intervention(s)

rezatapopt →pembrolizumab →

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.

Study 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.

Eligibility

Sex
ALL
Min age
12 Years
Max age
—
Healthy volunteers
No
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). Exception: Ovarian cancer patients with a known KRAS SNV are permitted. 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

Primary outcome measure(s)

  • Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt — 40 months
    Number of participants with treatment related adverse events
  • Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) — 30 months
    RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
  • Phase 1 Monotherapy (Dose Escalation): Establish the maximum tolerated dose (MTD) (Phase 1) — The first 28 days of treatment (Cycle 1) per patient
    Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
  • 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 — 18 months for treatment arm
    Number of participants with treatment related adverse events
  • Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the maximum tolerated dose (MTD) of rezatapopt when administered in combination with pembrolizumab — The first 28 days of combination treatment arm (starting on Day -7) per patient
    Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
  • Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) of rezatapopt when administered in combination with pembrolizumab — 18 months
    RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
  • 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 — 12 months for treatment arm
    Number of participants with treatment related adverse events
  • Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt — 34 months
    Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review across all cohorts
  • Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt in ovarian cancer patients — 34 months
    Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review in the ovarian cancer cohort

Trial sites (76)

FacilityCityRegionStatus
University of California Irvine Chao Family Comprehensive Cancer Center Irvine California Withdrawn
University of San Diego Moores Cancer Center La Jolla California Recruiting
UCLA Jonsson Comprehensive Cancer Center Los Angeles California Recruiting
USC Norris Comprehensive Cancer Center Los Angeles California Recruiting
Rocky Mountain Cancer Center Denver Colorado Recruiting
Yale Cancer Center New Haven Connecticut Recruiting
Medical Oncology Hematology Consultants Newark Delaware Recruiting
University of Miami - Sylvester Comprehensive Cancer Center Miami Florida Recruiting
Advent Health Orlando Florida Recruiting
Florida Cancer Specialists South Port Charlotte Florida Recruiting
Massachusetts General Hospital Boston Massachusetts Recruiting
Dana Farber Cancer Institute Boston Massachusetts Recruiting
Karmanos Cancer Institute Detroit Michigan Completed
Columbia University Medical Center New York New York Not Yet Recruiting
Memorial Sloan Kettering New York New York Recruiting
Duke University Durham North Carolina Recruiting
The Cleveland Clinic Taussig Cancer Center Cleveland Ohio Recruiting
University of Oklahoma Oklahoma City Oklahoma Recruiting
Oregon Health & Science University (OHSU) Portland Oregon Recruiting
Abramson Cancer Center of the University of Pennsylvania Philadelphia Pennsylvania Recruiting
University of Pittsburgh Medical Center Pittsburgh Pennsylvania Recruiting
WellSpan York Cancer Center York Pennsylvania Recruiting
Medical University of South Carolina Charleston South Carolina Terminated
Sarah Cannon Research Institute Nashville Tennessee Recruiting
New Experimental Therapeutics - NEXT Oncology Austin Texas Recruiting
Texas Oncology Bedford Texas Recruiting
UT Southwest Simmons Cancer Center Dallas Texas Recruiting
The University of Texas MD Anderson Cancer Center Houston Texas Recruiting
New Experimental Therapeutics of San Antonio - NEXT Oncology San Antonio Texas Recruiting
Virginia Cancer Specialists Fairfax Virginia Recruiting
University of Washington, Fred Hutchinson Cancer Center Seattle Washington Recruiting
University of Wisconsin Carbone Cancer Center Madison Wisconsin Recruiting
Chris O'Brien Lifehouse Hospital Camperdown New South Wales Recruiting
Mater Cancer Care Centre South Brisbane Queensland Recruiting
Flinders Medical Center Bedford Park South Australia Recruiting
Monash Medical Centre Clayton Victoria Recruiting
Linear Clinical Research Nedlands Western Australia Recruiting
ICANS - Institut de cancérologie Strasbourg Europe Strasbourg Bas-Rhin Recruiting
Institut Bergonie Bordeaux Gironde Recruiting
Institut Claudius Regaud Toulouse Haute-Garonne Recruiting

+ 36 more sites — see the full list on the official registry below.

On this site

📄 Keytruda (pembrolizumab) drug profile →

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04585750 on ClinicalTrials.gov ↗ ← All trials in France