Summary

Eligibility
for people ages 12 years and up (full criteria)
Location
at UCSD
Dates
study started
completion around

Description

Summary

This Phase 1/2 study will assess the safety, tolerability, and efficacy of multiple dose levels of PC14586 (INN: rezatapopt) alone (monotherapy) and in combination with pembrolizumab in participants with advanced solid tumors containing a TP53 Y220C mutation.

Official Title

A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of PC14586 in Patients With Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

Details

PC14586 (INN: rezatapopt) is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.

The primary objective of Phase 1 Monotherapy is to establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of PC14586 (INN: rezatapopt). Secondary objectives are to characterize the pharmacokinetic (PK) properties, safety and tolerability, and to assess preliminary efficacy including overall response rate (ORR).

The primary objective of Phase 1b Combination Therapy is to establish the MTD/RP2D of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab. Secondary objectives of Phase 1b Combination Therapy are to characterize PK, safety and tolerability, and to assess preliminary efficacy of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab, including ORR.

The primary objective of Phase 2 Monotherapy is to evaluate the efficacy of PC14586 (INN: rezatapopt) at the RP2D including the ORR in the Ovarian Cancer Cohort and the ORR across all cohorts as determined by blinded independent central review. Secondary objectives of Phase 2 are to characterize the safety, PK properties, quality of life, and other efficacy measures of PC14586 (INN: rezatapopt) at the RP2D.

Keywords

Advanced Solid Tumor, Advanced Malignant Neoplasm, Metastatic Cancer, Metastatic Solid Tumor, Lung Cancer, Ovarian Cancer, Endometrial Cancer, Prostate Cancer, Colorectal Cancer, Breast Cancer, Other Cancer, Locally Advanced, Head and Neck Cancer, 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, Neoplasms, Endometrial Neoplasms

Eligibility

You can join if…

Open to people ages 12 years and up

  • At least 18 years of age or 12 to 17 years of age after Safety Review Committee approval.
  • Advanced 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 (PC14586 (INN: rezatapopt) + pembrolizumab combination)

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

You CAN'T join if...

  • Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug
  • Radiotherapy within 28 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, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities
  • Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc prolongation, or proton pump inhibitors
  • 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 (PC14586 monotherapy)

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

    Additional Criteria for Exclusion from Phase 1b (PC14586 (INN: 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 PC14586 (INN: rezatapopt)

Locations

  • University of California, San Diego not yet accepting patients
    La Jolla California 92093 United States
  • USC Norris Comprehensive Cancer Center accepting new patients
    Los Angeles California 90033 United States
  • Oregon Health & Science University (OHSU) accepting new patients
    Portland Oregon 97210 United States

Details

Status
accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
(estimated)
Sponsor
PMV Pharmaceuticals, Inc
ID
NCT04585750
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 230 study participants
Last Updated