Evaluating PC14586 for advanced solid tumors with a specific mutation

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial evaluates the safety and efficacy of PC14586, a novel oral small molecule designed to reactivate the p53 protein, in patients with advanced solid tumors that have a TP53 Y220C mutation. The study consists of two phases: Phase 1 focuses on determining the maximum tolerated dose and preliminary efficacy of PC14586, while Phase 2 assesses its effectiveness as a monotherapy in various cancer cohorts. Additionally, there is a Phase 1b component that explores the combination of PC14586 with pembrolizumab, an immune checkpoint inhibitor. Enrollment is currently open for the Phase 2 portion of the study.

Why it matters

Who can join: the full rules

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

Where it's running

• University of San Diego Moores Cancer Center
  La Jolla, California, United States Recruiting
• UCLA Jonsson Comprehensive Cancer Center
  Los Angeles, California, United States Recruiting
• USC Norris Comprehensive Cancer Center
  Los Angeles, California, United States Recruiting
• Rocky Mountain Cancer Center
  Denver, Colorado, United States Recruiting
• Yale Cancer Center
  New Haven, Connecticut, United States Recruiting
• Medical Oncology Hematology Consultants
  Newark, Delaware, United States Recruiting

+26 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: PMV Pharma Clinical Study Information Center
• Email: clinicaltrials@pmvpharma.com
• Phone: (609) 235-4038

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Testing MGC026 in patients with advanced solid tumors

  This study is testing a new treatment called MGC026 to see if it can help adults with advanced solid tumors that can't be removed or have spread to other parts of the body.

  Recruiting at 12 sites Phase 1 MacroGenics · Los Angeles, California and 11 other locations · NCT06242470

• CAIX-targeted 18F-T2 PET/CT imaging in solid tumors

  This study tests a CAIX-specific radioactive tracer to see if PET/CT can help visualize solid tumors and checks safety and radiation exposure in adults with certain cancers.

  Recruiting Peking University First Hospital · Beijing, Beijing Municipality · NCT07557225

• Virtual exercise program to preserve function and prevent disability during chemotherapy

  This trial tests whether supervised resistance sessions by video plus short home aerobic workouts help adults 18–64 maintain strength and stay active while receiving curative-intent chemotherapy.

  Recruiting at 29 sites Alliance for Clinical Trials in Oncology · Dublin, California and 29 other locations · NCT07059884

• Validation of a blood test for early cancer detection and monitoring

  This study is testing a blood test to see if it can help find different types of cancer early and monitor patients after treatment.

  Recruiting at 3 sites Adela, Inc · Duarte, California and 16 other locations · NCT05366881

• Evaluating progastrin levels in cancer patients

  This study is testing if measuring progastrin levels in the blood can help predict how cancer will progress and respond to treatment in patients with different types of cancer.

  Recruiting at 17 sites Hospices Civils de Lyon · Bron and 16 other locations · NCT03787056

• Testing trastuzumab deruxtecan (T‑DxD) for HER2‑positive advanced solid tumors

  This will test whether trastuzumab deruxtecan (T‑DxD) helps adults in the US with HER2‑positive (IHC 3+) locally advanced, unresectable, or metastatic solid tumors who have had prior systemic treatment and have no satisfactory alternative options.

  Recruiting at 18 sites AstraZeneca · Birmingham, Alabama and 17 other locations · NCT07124000

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.