PMV Pharmaceuticals Announces Updated Rezatapopt Monotherapy Interim Data From Ongoing PYNNACLE Phase 2 Trial Across Multiple Solid Tumors With a TP53 Y220C Mutation
PMV Pharmaceuticals (Nasdaq: PMVP) reported updated Phase 2 PYNNACLE monotherapy data for rezatapopt (TP53 Y220C) with a 34% ORR across 103 evaluable patients and median duration of response of 7.6 months (data cutoff Sept 4, 2025). Confirmed responses appeared in eight tumor types including ovarian, lung, breast, endometrial, head and neck, colorectal, gallbladder, and ampullary cancer.
The ovarian cohort showed a 46% ORR (22/48) with median duration of response 8.0 months. Safety was mostly Grade 1–2; Grade 3 TRAEs ≤6% and drug discontinuations due to TRAEs were 3.6%. An NDA for platinum-resistant/refractory ovarian cancer is planned for Q1 2027.
PMV Pharmaceuticals (Nasdaq: PMVP) ha riferito dati aggiornati di fase 2 PYNNACLE monoterapia per rezatapopt (TP53 Y220C) con un ORR del 34% su 103 pazienti valutabili e una durata mediana della risposta di 7,6 mesi (cutoff dei dati al 4 settembre 2025). Le risposte confermate sono emerse in otto tipi di tumore tra cui ovaio, polmone,
La coorte ovarica ha mostrato un ORR del 46% (22/48) con una durata media della risposta di 8,0 mesi. La sicurezza è stata principalmente di grado 1–2; eventi avversi legati al trattamento di grado 3 ≤6% e le interruzioni del trattamento dovute a TRAE sono 3,6%. È previsto un NDA per il cancro ovarico resistente/refrattario al platino per Q1 2027.
PMV Pharmaceuticals (Nasdaq: PMVP) informó datos actualizados de Fase 2 PYNNACLE de monoterapia para rezatapopt (TP53 Y220C) con un ORR del 34% en 103 pacientes evaluables y una duración media de la respuesta de 7,6 meses (corte de datos al 4 de septiembre de 2025). Las respuestas confirmadas aparecieron en ocho tipos de tumores, incluyendo ovario, pulmón, mama, endometrio, cabeza y cuello, colorrectal, vesícula biliar y cáncer ampular.
La cohorte de ovario mostró un ORR del 46% (22/48) con una duración media de la respuesta de 8,0 meses. La seguridad fue principalmente de Grado 1–2; eventos adversos graves de grado 3 relacionados con el tratamiento ≤6% y las descontinuaciones por TRAEs fueron 3,6%. Se planea una NDA para cáncer de ovario resistente/refractorio al platino para Q1 2027.
PMV Pharmaceuticals (Nasdaq: PMVP)은 rezatapopt (TP53 Y220C) 치료제의 2상 PYNNACLE 단독요법 데이터를 업데이트하여 전체 평가환자 103명에서 34%의 ORR과 반응 지속 기간의 중앙값 7.6개월을 보고했습니다(데이터 마감일 2025년 9월 4일). 확인된 반응은 자궁난소암, 폐암, 유방암, 자궁내막암, 두경부암, 직장암, 담낭암, 그리고 어피움암을 포함한 8개 종양에서 나타났습니다.
난소 코호트에서 46%(22/48)의 ORR과 반응 지속 기간 8.0개월의 중앙값이 관찰되었습니다. 안전성은 주로 1–2등급이었고, 3등급 TRAE는 ≤6%, TRAE로 인한 약물 중단은 3.6%였습니다. 백금저항성/재발성 난소암에 대한 NDA는 2027년 1분기에 계획되어 있습니다.
PMV Pharmaceuticals (Nasdaq : PMVP) a rapporté des données mises à jour de la phase 2 PYNNACLE en monothérapie pour rezatapopt (TP53 Y220C) avec un ORR de 34% chez 103 patients évaluables et une durée médiane de réponse de 7,6 mois (date de coupure des données au 4 septembre 2025). Des réponses confirmées sont apparues dans huit types de tumeurs, dont l’ovaire, le poumon, le sein, l’endomètre, la tête et le cou, le colorectale, la vésicule biliaire et le cancer ampullaire.
La cohorte ovarienne a montré un ORR de 46% (22/48) avec une durée médiane de la réponse de 8,0 mois. La sécurité était principalement de grade 1–2; les TRAE de grade 3 étaient ≤6% et les discontinuations de traitement liées aux TRAE étaient 3,6%. Une NDA pour le cancer de l’ovaire résistant/refractory au platine est planifiée pour le 1er trimestre 2027.
PMV Pharmaceuticals (Nasdaq: PMVP) berichtete aktualisierte Phase-2-Daten von PYNNACLE als Monotherapie für rezatapopt (TP53 Y220C) mit einer ORR von 34% bei 103 evaluierten Patienten und einer mittleren Ansprechdauer von 7,6 Monaten (Daten-Cutoff 4. September 2025). Bestätigte Antworten traten in acht Tumortypen auf, darunter Ovarialkarzinom, Lungenkrebs, Brustkrebs, Endometriumkarzinom, Kopf- und Halsbereich, kolorektaler Krebs, Gallenblasenkrebs und Ampullenkrebs.
Die Ovarialkohorte zeigte ein ORR von 46% (22/48) mit einer mittleren Ansprechdauer von 8,0 Monaten. Die Sicherheit war überwiegend Grad 1–2; Grad-3-TRAEs ≤6% und Absetzungen aufgrund von TRAEs 3,6%. Eine NDA für platinresistentes/refraktäres Ovarialkarzinom ist für das 1. Quartal 2027 geplant.
PMV Pharmaceuticals (نَصْدَاق: PMVP) أبلغت عن بيانات محدثة من المرحلة الثانية في PYNNACLE كعلاج وحيدي لـ rezatapopt (TP53 Y220C) بمعدل استجابة ورؤية مرضية ORR 34% لدى 103 مرضى قابلين للتقييم وبمتوسط مدة الاستجابة 7.6 أشهر (آخر تاريخ للبيانات 4 سبتمبر 2025). ظهرت استجابات مؤكدة في ثمانية أنواع أورام بما في ذلك المبيض، الرئة، الثدي، بطانة الرحم، الجمجمة والرقبة، المعِدْلة المعِدّلة، مثانة المرارة وسرطان المصعد (الأمبولاري).
المجموعة الخاصة بالمبيض أظهرت ORR 46% (22/48) مع مدة استجابة وسطى 8.0 أشهر. الأمان كان في الغالب من الدرجة 1–2؛ حدوث TRAEs من الدرجة 3 ≤6% ووقف الدواء بسبب TRAEs كان 3.6%. من المخطط تقديم NDA لسرطان المبيض المقاوم/غير المستجيب للبلاتين في الربع الأول من 2027.
- Overall response rate 34% across 103 evaluable patients
- Ovarian cohort ORR 46% (22/48) with median DOR 8.0 months
- Median duration of response 7.6 months across cohorts
- Low discontinuation rate due to TRAEs at 3.6%
- Safety events included Grade 3 TRAEs up to 6% for individual events
- Efficacy cohorts included small sample sizes for several tumor types (eg, endometrial 5 patients)
Insights
Phase 2 PYNNACLE shows meaningful tumor responses and a planned NDA submission for platinum‑resistant ovarian cancer in
The drug produced a
Regulatory path depends on durability, safety, and confirmatory data. Safety findings were mainly Grade 1–2, Grade 3 events were ≤
Key near‑term items to watch include final confirmation of unconfirmed responses, any centralized radiology read versus investigator assessment, cumulative safety with larger exposure, and the datasets the company files with the NDA expected in the leadup to
- Data presented today as an oral presentation at 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
- Confirmed responses observed in eight tumor types spanning ovarian, lung, breast, endometrial, head and neck, colorectal, gallbladder, and ampullary carcinoma
34% overall response rate (ORR) observed among 103 evaluable patients across all cohorts with a median duration of response of 7.6 months46% ORR observed among 48 evaluable patients in ovarian cancer cohort with a median duration of response of 8.0 months- Rezatapopt New Drug Application submission for platinum-resistant/refractory ovarian cancer planned in first quarter of 2027
PRINCETON, N.J., Oct. 24, 2025 (GLOBE NEWSWIRE) -- PMV Pharmaceuticals, Inc. (“PMV Pharma” or the “Company”; Nasdaq: PMVP), a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53, today announced updated data from the Phase 2 pivotal portion of the ongoing PYNNACLE clinical trial. Results were presented today in an oral presentation by Alison M. Schram, M.D., Medical Oncologist at Memorial Sloan Kettering Cancer Center and PYNNACLE Study Investigator, at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics taking place in Boston, Massachusetts. The ongoing Phase 1/2 PYNNACLE clinical trial is evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation.
“Patients with TP53 Y220C-mutated advanced solid tumors are in need of better treatment options, particularly those with platinum-resistant and refractory ovarian cancer. The rezatapopt data presented today demonstrate very encouraging clinical activity, reinforcing the potential for rezatapopt to target the underlying biology of these cancers and providing a potential shift in the current treatment paradigm,” said Dr. Schram.
The Phase 2 clinical trial data below are summarized as of a September 4, 2025 data cutoff date:
- The safety population consisted of 112 patients treated with at least one dose of rezatapopt 2000mg daily as monotherapy.
- Median number of prior lines of systemic therapy was three (range: 1-10)
- The efficacy population consisted of 103 patients treated with at least one dose of rezatapopt as of the data cutoff date and either had ≥1 post-baseline tumor assessment or discontinued early.
Efficacy
- Confirmed responses were observed in patients whose tumors were TP53 Y220C mutated and KRAS wild-type in eight tumor types including ovarian, lung, breast, endometrial, head and neck, colorectal, gallbladder cancers, and ampullary carcinoma.
- Overall response rate (ORR) of
34% (35/103 patients) per investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including confirmed and unconfirmed responses. - The cohort-specific ORRs were as follows:
- Ovarian cancer:
46% ORR (22/48 patients, including one confirmed complete response, 18 confirmed partial responses, and three unconfirmed partial responses [uPR]) - Breast cancer:
17% ORR (2/12 patients) - Endometrial cancer:
60% ORR (3/5 patients, including one uPR) - Lung cancer:
21% ORR (4/19 patients, including one uPR) - Other solid tumors:
21% ORR (4/19 patients)
- Ovarian cancer:
- Across all cohorts, the median time to response was 1.3 months and the median duration of response was 7.6 months.
- In the ovarian cancer cohort, the median time to response was 1.3 months and median duration of response was 8.0 months.
- Post the September 4, 2025 data cutoff date, four uPRs were confirmed and one uPR (ovarian cancer) remains on treatment.
Safety
- Treatment-related adverse events (TRAEs) were mostly Grade 1-2 with the most frequent TRAEs observed (>
15% ) being nausea, fatigue, blood creatinine increased, and alanine aminotransferase (ALT) increased. The rates of individual Grade 3 TRAEs were ≤6% . All Grade 3 TRAEs resolved on treatment and there were no discontinuations due to Grade 3 aspartate aminotransferase (AST)/ALT elevations. - Rezatapopt administration with food led to an improvement in gastrointestinal tolerability relative to Phase 1 data.
- Lab abnormalities were manageable, with the majority of cases being transient and reversible.
- The rate of drug discontinuations due to a TRAE was
3.6% .
“We are pleased to share these updated results from the pivotal portion of the ongoing PYNNACLE trial, which continue to enhance our understanding about the potential of rezatapopt to deliver deep and durable responses in patients with limited targeted treatment options. The improvements in overall response rates and median duration of response across all cohorts and specifically in the ovarian cancer cohort are encouraging and further support the potential of rezatapopt to meaningfully impact outcomes for patients with TP53 Y220C mutated advanced tumors,” said Deepika Jalota, Pharm.D., Chief Development Officer of PMV Pharma. “We remain on track to submit an NDA in the first quarter of 2027 for platinum-resistant/refractory ovarian cancer, while continuing to generate additional data to support our broader regulatory strategy.”
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 tumor-suppressor function. The U.S. Food and Drug Administration granted Fast Track designation to rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors with a p53 Y220C mutation.
About the PYNNACLE Clinical Trial
The ongoing Phase 1/2 PYNNACLE clinical trial is evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation. The primary objective of the Phase 1 portion of the clinical 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 were also assessed. The Phase 2 portion is a registrational, single arm, expansion basket clinical trial comprising five cohorts (ovarian, lung, breast, and endometrial cancers, and other solid tumors) with the primary objective of evaluating the efficacy of rezatapopt at the RP2D in patients with TP53 Y220C and KRAS wild-type advanced solid tumors. For more information about the Phase 1/2 PYNNACLE clinical trial, refer to www.clinicaltrials.gov (NCT trial 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. TP53 mutations are found in approximately half of all cancers. The Company’s co-founder, Dr. Arnold Levine, established the field of p53 biology when he discovered the p53 protein in 1979. Bringing together leaders in the field to utilize more than four decades of p53 biology, PMV Pharma combines unique biological understanding with a pharmaceutical development focus. PMV Pharma is headquartered in Princeton, New Jersey. For more information, please visit www.pmvpharma.com.
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 clinical development activities, plans and projected timelines for rezatapopt, including expectations regarding the timing and completion of patient enrollment and ultimate completion of the Phase 2 portion of the PYNNACLE study, the timing of disclosures regarding clinical data updates of its current clinical trial for rezatapopt, expected therapeutic benefits of rezatapopt including potential efficacy and tolerability, plans regarding regulatory filings and approvals, including targeted timelines for the Company’s New Drug Application submission and initial U.S. Food and Drug Administration (FDA) approval for platinum-resistant or refractory ovarian indication, ongoing safety and response rate of participants in the PYNNACLE study, as well as the overall timing and success of the Company’s current and future clinical trials for rezatapopt, the adequacy of the data to support the Company’s pursuit of regulatory approval, and the Company’s expectations regarding the therapeutic, addressable patient populations, timing for approval, and commercial potential of rezatapopt. 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 Company’s preclinical studies and clinical trials may not be successful; the FDA may not agree with the Company’s interpretation of the data from clinical trials of its product candidates; the Company may decide, or the FDA may require the Company, to conduct additional clinical trials or to modify its ongoing clinical trials, which could result in enrollment or other delays to the Company’s anticipated timelines; the Company may experience delays in the commencement, enrollment, completion, or analysis of clinical testing for its product candidates, or significant issues regarding the adequacy of the Company’s clinical trial designs or the execution of its clinical trials may arise, which could result in increased costs and delays, or limit the Company’s ability to pursue or obtain regulatory approval; the commencement, enrollment, and completion of clinical trials and the reporting of data; a global pandemic, other public health emergencies or geopolitical tensions or conflicts may disrupt the Company’s business and that of the third parties on which the Company is dependent on, including delaying or otherwise disrupting the Company’s clinical trials and preclinical studies, manufacturing and supply chain, or impairing employee productivity; the Company’s product candidates may not receive regulatory approval or be successfully commercialized; unexpected adverse side effects or inadequate therapeutic efficacy of the Company’s product candidates could delay or prevent regulatory approval or commercialization; the Company may not be able to obtain additional financing on terms acceptable or at all; as well as those risks and uncertainties set forth in the sections entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in the Company’s Annual Report on Form 10-K, filed with the Securities and Exchange Commission (the “SEC”) on March 3, 2025, the Company’s Quarterly Report on Form 10-Q for the three months ended March 31, 2025, filed with the SEC on May 9, 2025, and the Company’s Quarterly Report on Form 10-Q for the three months ended June 30, 2025, filed with the SEC on August 7, 2025, and its other filings filed with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Contacts
Investors Contact:
Tim Smith
Senior Vice President, Head of Corporate Development and Investor Relations
investors@pmvpharma.com
Media Contact:
Kathy Vincent
Greig Communications
kathy@greigcommunications.com
FAQ
What was the overall response rate for rezatapopt in the PYNNACLE Phase 2 trial (data cutoff Sept 4, 2025)?
What response did PMVP report for the ovarian cancer cohort (rezatapopt, PYNNACLE)?
What is the median duration of response reported for rezatapopt across PYNNACLE cohorts?
What safety profile did PMVP report for rezatapopt monotherapy in PYNNACLE?
Will PMV Pharmaceuticals submit an NDA for rezatapopt and when (PMVP)?
Which tumor types showed confirmed responses to rezatapopt in the PYNNACLE trial?
