- Phase 1 analysis from the PYNNACLE Phase 1/2 study showed promising efficacy of rezatapopt (PC14586) in heavily pre-treated patients with advanced ovarian cancer harboring a TP53 Y220C mutation featured in a late-breaking oral presentation at 2024 SGO Annual Meeting
- Of the 15 patients in the efficacy evaluable population, seven patients achieved a confirmed partial response with a seven-month median duration of response and a favorable safety profile
- Rezatapopt is a first-in-class precision oncology investigational therapy in patients with advanced solid tumors with a TP53 Y220C mutation and KRAS wild-type which is being evaluated in a registrational Phase 2 study
These data were featured today in a late-breaking oral presentation at the 2024
“In this Phase 1 study, we observed promising efficacy of rezatapopt in heavily pre-treated patients with advanced ovarian cancer harboring a TP53 Y220C mutation. In addition, rezatapopt showed a favorable safety profile,” said
Results of Phase 1 Analysis of PYNNACLE in Advanced Ovarian Cancer
Phase 1 data from the PYNNACLE trial (NCT04585750) demonstrated that rezatapopt has a favorable safety profile and induced responses in heavily pre-treated patients across multiple tumor types. This subgroup analysis investigated the efficacy of rezatapopt in patients with advanced ovarian cancer treated across the efficacious dose range (1150 mg daily to 1500 mg twice daily).
Patient Characteristics
- As of
September 5, 2023 , the median age of patients with ovarian cancer (N=22) was 66 years (range 49 – 81 years) - At baseline, 20 patients had high-grade serous ovarian cancer and two had endometrioid cancer
- Nineteen patients were platinum resistant and one was platinum refractory
- Two patients had a BRCA2 mutation
- Six patients were homologous recombination deficiency positive
- All patients were KRAS wild-type
- Median number of prior lines of systemic therapy was four (range 1 – 9)
Efficacy
The efficacy evaluable population consisted of 15 patients with measurable disease at baseline and ≥1 post-baseline tumor assessment.
- Seven patients achieved a confirmed partial response (PR), seven had stable disease (SD), and one had progressive disease
- Median duration of response was seven months
- Of the 15 patients with measurable serum CA-125 at baseline, six had a CA-125 response. Among these, five patients achieved radiographic PR and one had SD
Safety
In the overall population of 67 patients assessed in the efficacious dose range (≥1150mg daily), including this subset of patients with ovarian cancer, treatment-related adverse events (TRAEs) were mostly grade 1 and 2.
- Most frequent TRAEs were nausea (51%), vomiting (43%), and increased blood creatinine (27%)
- Frequency and severity of TRAEs were similar in the ovarian cancer population compared with the overall population
- Rezatapopt administration with food led to an improvement in nausea and vomiting
About Rezatapopt
Rezatapopt (PC14586) is a first-in-class, small molecule, p53 reactivator designed to selectively bind to the pocket in the p53 Y220C mutant protein, restoring the wild-type, or normal, p53 protein structure and tumor-suppressing function. The
About the PYNNACLE Clinical Trial
The ongoing Phase 1/2 PYNNACLE study is evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation. The primary objective of the Phase 1 portion of the trial was to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) of rezatapopt when administered orally to patients. Safety, tolerability, pharmacokinetics and effects on biomarkers will also be assessed. Phase 2 will be an expansion study with the primary objective of evaluating the efficacy of rezatapopt at the RP2D in patients with TP53 Y220C advanced solid tumors. For more information about the Phase 1/2 PYNNACLE clinical trial, refer to www.clinicaltrials.gov (NCT study identifier NCT04585750).
About PMV Pharma
PMV Pharma is a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53. p53 mutations are found in approximately half of all cancers. Our co-founder, Dr.
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the Company’s future plans or expectations for rezatapopt, including our ability to obtain approval on a tumor-agnostic basis, ongoing safety and response rate of participants in our clinical trials and expectations regarding timing and success of the Phase 2 portion of its current clinical trial for rezatapopt, including rezatapopt’s potential efficacy and safety profile in ovarian cancer patients. Any forward-looking statements in this statement are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of the Company’s product candidate development activities and planned clinical trials, the Company’s ability to execute on its strategy and operate as a clinical stage company, the potential for clinical trials of rezatapopt or any future clinical trials of other product candidates to differ from preclinical, preliminary, interim or expected results, the Company’s ability to fund operations, and the impact that any current or future global pandemic or geopolitical emergency may have on the Company’s clinical trials, supply chain, and operations, as well as those risks and uncertainties set forth in the section entitled “Risk Factors” in the Company’s Annual Report on Form 10-K filed with the
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Source:
2024 GlobeNewswire, Inc., source