Description:
This study will assess the safety and tolerability of multiple dose levels of PC14586 in
participants with advanced solid tumors containing a p53 Y220C mutation.
Title
- Brief Title: The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 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 Advanced Solid Tumors Harboring a p53 Y220C Mutation
Clinical Trial IDs
- ORG STUDY ID:
PMV-586-101
- NCT ID:
NCT04585750
Conditions
- Advanced Solid Tumor
- Advanced Malignant Neoplasm
- Metastatic Cancer
- Metastatic Solid Tumor
Interventions
| Drug | Synonyms | Arms |
|---|
| PC14586 | | Phase 1 Dose Escalation |
Purpose
This study will assess the safety and tolerability of multiple dose levels of PC14586 in
participants with advanced solid tumors containing a p53 Y220C mutation.
Detailed Description
PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the
p53 Y220C mutation. The trial will be conducted in 2 parts: dose escalation (Phase 1) and
dose expansion (Phase 2).
The primary objective of Phase 1 is to establish the maximum tolerated dose / recommended
dose of PC14586 to treat participants with advanced solid tumors harboring a p53 Y220C
mutation. Secondary objectives of Phase 1 are to characterize the pharmacokinetic properties
of the investigational drug, its safety and tolerability, and to assess the overall response
rate (ORR).
The primary objective of Phase 2 is to assess the ORR in participants with advanced solid
tumors harboring a p53 Y220C mutation as determined by an independent radiology committee.
Secondary objectives of Phase 2 include the safety, pharmacokinetic properties, and efficacy
of PC14586 at the recommended dose.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Phase 1 Dose Escalation | Experimental | Multiple dose levels of PC14586 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). | |
| Phase 2 Dose Expansion, Cohort A | Experimental | Additional (expansion of) participants will enroll at the RP2D of PC14586 for continued evaluation. Cohort A participants will have advanced solid tumors harboring a p53 Y220C mutation who meet all eligibility criteria and have measureable disease per RECIST 1.1. | |
| Phase 2 Dose Expansion, Cohort B | Experimental | Additional (expansion of) participants will enroll at the RP2D of PC14586 for continued evaluation. Cohort B participants will have advanced solid tumors harboring a p53 Y220C mutation who do not meet all eligibility criteria (e.g. have a primary central nervous system (CNS) tumor) and do not have measurable disease per RECIST 1.1. | |
Eligibility Criteria
Inclusion Criteria:
- At least 18 years of age or 12 to 17 years of age after adequate adult safety data
become available
- Advanced solid malignancy with a p53 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
Exclusion Criteria:
- 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 (Phase 1, Phase 2 Cohort A)
- History of leptomeningeal disease or spinal cord compression
- Brain metastases, unless asymptomatic and not requiring steroids for at least 2 weeks
prior to receiving the study drug
- 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 12 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Determine the number and type of adverse events to characterize the safety of PC14586 |
| Time Frame: | 48 months for study (Phase 1 and 2) |
| Safety Issue: | |
| Description: | Number of participants with treatment related adverse events |
Secondary Outcome Measures
| Measure: | Blood plasma assessment to characterize the pharmacokinetics (PK) of PC14586 and metabolites (Phase 1 and 2) |
| Time Frame: | Approximately 12 months per patient (48 months for study) |
| Safety Issue: | |
| Description: | Blood plasma concentration |
| Measure: | Response rate assessment to assess clinical activity / efficacy of PC14586 (Phase 1) |
| Time Frame: | 20 months for study (end of Phase 1) |
| Safety Issue: | |
| Description: | Overall response rate in accordance with Response Evaluation Criteria in Solid Tumors |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | PMV Pharmaceuticals, Inc |
Trial Keywords
- PC14586
- p53
- Y220C
- Phase 1
- Phase 1/2
- PMV
- PMV Pharma
- p53 mutation
- TP53
- TP53 mutation
- p53 mutant
- p53 reactivator
Last Updated
June 14, 2021
