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

Launched by PMV PHARMACEUTICALS, INC · Oct 7, 2020

Keywords

ClinConnect Summary

The PYNNACLE clinical trial is studying a new treatment called PC14586, aimed at patients with advanced solid tumors that have a specific genetic mutation known as TP53 Y220C. This trial is currently looking for participants to evaluate how safe and effective this treatment is when given alone or in combination with another drug called pembrolizumab. The goal is to see if PC14586 can help those who have already tried other cancer treatments but continue to have worsening disease.

To be eligible for the trial, participants need to be at least 18 years old (or between 12 and 17 with special approval) and have an advanced solid tumor with the TP53 Y220C mutation. They should have received prior cancer treatments and have measurable disease. Participants can expect to undergo regular monitoring to assess their health and how well the treatment is working. It's important to note that there are specific criteria for exclusion, meaning some people with certain health conditions or previous treatments may not be able to join. Overall, this trial offers a potential new option for those facing advanced cancers with particular genetic characteristics.

Gender

ALL

Eligibility criteria

• 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 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 inducers
• • 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