PMV Pharmaceuticals Provides a Progress Update on PYNNACLE Clinical Trial
PMV Pharmaceuticals provided updates on its PYNNACLE clinical trial for rezatapopt. The Phase 2 monotherapy portion is progressing well, with >75% of sites activated globally and interim analysis expected by mid-2025. However, the company is discontinuing the Phase 1b combination arm with KEYTRUDA due to dose-limiting toxicities and clinical benefit. The maximum tolerated dose was established at rezatapopt 500mg daily with pembrolizumab 200mg every three weeks.
Additionally, PMV announced collaboration with MD Anderson and Memorial Sloan Kettering for a new Phase 1b study evaluating rezatapopt in AML/MDS patients with TP53 Y220C mutation, starting Q1 2025.
PMV Pharmaceuticals ha fornito aggiornamenti sul suo trial clinico PYNNACLE per rezatapopt. La parte di monoterapia di Fase 2 sta procedendo bene, con oltre il 75% dei centri attivati a livello globale e un'analisi intermedia prevista per metà del 2025. Tuttavia, l'azienda sta interrompendo il braccio di combinazione di Fase 1b con KEYTRUDA a causa di tossicità limitanti della dose e benefici clinici. La dose massima tollerata è stata stabilita a rezatapopt 500mg al giorno con pembrolizumab 200mg ogni tre settimane.
Inoltre, PMV ha annunciato una collaborazione con MD Anderson e Memorial Sloan Kettering per un nuovo studio di Fase 1b che valuterà rezatapopt in pazienti con AML/MDS con mutazione TP53 Y220C, che inizierà nel primo trimestre del 2025.
PMV Pharmaceuticals proporcionó actualizaciones sobre su ensayo clínico PYNNACLE para rezatapopt. La parte de monoterapia de Fase 2 avanza bien, con más del 75% de los sitios activados a nivel mundial y un análisis intermedio esperado para mediados de 2025. Sin embargo, la empresa está descontinuando el brazo de combinación de Fase 1b con KEYTRUDA debido a toxicidades limitativas de dosis y beneficios clínicos. La dosis máxima tolerada se estableció en rezatapopt 500mg diarios con pembrolizumab 200mg cada tres semanas.
Además, PMV anunció una colaboración con MD Anderson y Memorial Sloan Kettering para un nuevo estudio de Fase 1b que evaluará rezatapopt en pacientes con AML/MDS con mutación TP53 Y220C, que comenzará en el primer trimestre de 2025.
PMV 제약회사는 rezatapopt의 PYNNACLE 임상 시험에 대한 업데이트를 제공했습니다. 2상 단일요법 부분은 전 세계적으로 75% 이상의 사이트가 활성화되며 순조롭게 진행되고 있으며, 중간 분석은 2025년 중반에 예정되어 있습니다. 그러나 회사는 용량 제한 독성과 임상적 이점으로 인해 KEYTRUDA와의 1b상 병합 시험을 중단하고 있습니다. 최대 허용 용량은 rezatapopt 500mg 매일과 pembrolizumab 200mg 3주마다로 설정되었습니다.
또한 PMV는 MD Anderson 및 Memorial Sloan Kettering과 협력하여 TP53 Y220C 변이를 가진 AML/MDS 환자에서 rezatapopt를 평가하는 새로운 1b상 연구를 2025년 1분기에 시작한다고 발표했습니다.
PMV Pharmaceuticals a fourni des mises à jour sur son essai clinique PYNNACLE pour rezatapopt. La partie monothérapie de Phase 2 progresse bien, avec plus de 75 % des sites activés à l'échelle mondiale et une analyse intermédiaire prévue pour mi-2025. Cependant, l'entreprise interrompt le bras de combinaison de Phase 1b avec KEYTRUDA en raison de toxicités limitantes de dose et de bénéfices cliniques. La dose maximale tolérée a été établie à rezatapopt 500 mg par jour avec pembrolizumab 200 mg toutes les trois semaines.
De plus, PMV a annoncé une collaboration avec MD Anderson et Memorial Sloan Kettering pour une nouvelle étude de Phase 1b évaluant rezatapopt chez des patients atteints d'AML/MDS avec la mutation TP53 Y220C, qui débutera au premier trimestre 2025.
PMV Pharmaceuticals hat Updates zu seiner PYNNACLE-Studie für rezatapopt bereitgestellt. Der Teil der Phase-2-Monotherapie verläuft gut, wobei mehr als 75 % der Standorte weltweit aktiviert wurden und eine Zwischenanalyse bis Mitte 2025 erwartet wird. Das Unternehmen stellt jedoch den Kombinationsarm der Phase 1b mit KEYTRUDA aufgrund von dosislimitierenden Toxizitäten und klinischem Nutzen ein. Die maximal tolerierte Dosis wurde auf rezatapopt 500 mg täglich mit pembrolizumab 200 mg alle drei Wochen festgelegt.
Zusätzlich gab PMV eine Zusammenarbeit mit MD Anderson und Memorial Sloan Kettering für eine neue Phase-1b-Studie bekannt, die rezatapopt bei AML/MDS-Patienten mit der TP53 Y220C-Mutation bewertet, die im ersten Quartal 2025 beginnt.
- Phase 2 monotherapy trial enrollment is on track with >75% site activation
- New Drug Application submission planned for end of 2026
- New Phase 1b study collaboration with prestigious cancer centers for AML/MDS treatment
- Discontinuation of Phase 1b combination trial with KEYTRUDA due to toxicities
- clinical benefit observed at maximum tolerated dose in combination therapy
- Multiple Grade 2 and 3 adverse events reported in combination therapy
Insights
This clinical trial update reveals significant developments for PMV Pharmaceuticals' rezatapopt program. The discontinuation of the pembrolizumab combination arm due to dose-limiting toxicities and clinical benefit at 500mg represents a setback in the combination strategy. However, the Phase 2 monotherapy trial continues to progress well with >75% site activation and remains on track for interim analysis by mid-2025.
The new collaboration with MDACC and MSK for AML/MDS patients opens a promising avenue in hematologic malignancies. This strategic pivot could potentially address an important unmet need in patients with TP53 Y220C mutations, who typically face poor prognosis. The planned combination with azacitidine in this setting appears more mechanistically sound than the failed PD-1 combination.
- Enrollment on track in registrational Phase 2 portion of PYNNACLE clinical trial evaluating rezatapopt as monotherapy in patients with TP53 Y220C and KRAS wild-type advanced solid tumors; more than
75% of sites activated across the U.S., Europe, and Asia-Pacific; interim analysis expected by mid-2025
- Dose-limiting toxicities observed in rezatapopt and Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) combination arm of Phase 1b PYNNACLE trial; rezatapopt 500 mg once-daily in combination with pembrolizumab 200 mg every three weeks established as maximum tolerated dose; due to limited clinical benefit at this dose, PMV is discontinuing enrollment in the Phase 1b combination arm
- PMV Pharmaceuticals is collaborating with MD Anderson Cancer Center (MDACC) and Memorial Sloan Kettering Cancer Center (MSK) to support an investigator-initiated Phase 1b study evaluating rezatapopt monotherapy and in combination with azacitidine in patients with recurrent or refractory AML/MDS harboring a TP53 Y220C mutation
PRINCETON, N.J., Oct. 23, 2024 (GLOBE NEWSWIRE) -- PMV Pharmaceuticals, Inc. (Nasdaq: PMVP), a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53, today provided an update on the Phase 2 monotherapy and Phase 1b combination portions of the ongoing PYNNACLE clinical trial.
PYNNACLE Phase 2 Monotherapy Update
Enrollment is on track in the Phase 2 monotherapy portion of the PYNNACLE clinical trial. The multicenter, single-arm, registrational, tumor-agnostic Phase 2 trial is assessing rezatapopt as monotherapy at a dose of 2000 mg once-daily in patients with TP53 Y220C and KRAS wild-type advanced solid tumors. The primary endpoint of the trial is overall response rate per blinded independent central review. The trial is designed to enroll 114 patients across five cohorts at approximately 60 sites.
More than
PYNNACLE Phase 1b Rezatapopt in Combination with Pembrolizumab Update
PMV has decided to discontinue enrollment in the Phase 1b combination arm of the PYNNACLE trial evaluating rezatapopt in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with advanced solid tumors harboring a TP53 Y220C mutation. Nineteen patients were enrolled in the combination arm of the trial. This decision was driven by dose-limiting toxicities (DLTs) observed at the 1000 mg dose of rezatapopt once-daily plus pembrolizumab 200 mg every three weeks. The DLTs were Grade 2 and 3 and included AST increase, platelet count decrease, pancreatitis, dehydration, and rash. No Grade 4 or 5 adverse events were observed. The safety profile of the rezatapopt and pembrolizumab combination has been consistent with each agent as monotherapy with no new safety signals observed.
Per protocol, these observations established rezatapopt 500 mg once-daily in combination with pembrolizumab 200 mg every three weeks as the maximum tolerated dose. Patients dosed with rezatapopt 500 mg once-daily in combination with pembrolizumab did not experience a clinically meaningful benefit, informing the decision to discontinue enrollment in the combination arm of the PYNNACLE trial.
MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center to Initiate a Phase 1b Study in Recurrent/Refractory AML/MDS
PMV Pharma is collaborating with MD Anderson Cancer Center (MDACC) and Memorial Sloan Kettering Cancer Center (MSK) to support an investigator-initiated Phase 1b study. The study is designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of rezatapopt monotherapy and in combination with azacitidine in approximately 25 patients with recurrent or refractory acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS) harboring a TP53 Y220C mutation. Enrollment is planned to begin in the first quarter of 2025 across two sites.
“There is an important need for new treatment options for patients with recurrent or refractory AML or MDS harboring a TP53 Y220C mutation, as this mutation is often associated with poorer prognosis and resistance to conventional therapies” said Courtney DiNardo M.D., MSCE, Department of Leukemia, Division of Cancer Medicine at MDACC. “Based on proof-of-concept data demonstrating the ability of rezatapopt to selectively reactivate p53 in locally advanced/metastatic solid tumor patients with a TP53 Y220C mutation, we believe that rezatapopt in combination with azacitidine has the potential to significantly benefit this patient population.”
Eytan M. Stein, M.D., Chief, Leukemia Service at MSK commented, “Patients with p53 mutant AML currently have no effective standard of care treatment options that lead to long term survival, so this important trial using rezatapopt is the first step in developing a focused, mutation specific strategy, for this patient population.”
David Mack, Ph.D., President and Chief Executive Officer of PMV Pharma commented, “While we are disappointed to discontinue enrollment of the trial evaluating rezatapopt in combination with pembrolizumab, we look forward to the initiation of the AML/MDS study and evaluating rezatapopt in other settings. I would like to thank the patients and investigators for their time and commitment to the Phase 1b combination portion of the PYNNACLE study. We remain excited by the potential for rezatapopt as a monotherapy in patients with advanced solid tumors harboring a TP53 Y220C mutation and KRAS wild-type and look forward to providing interim data in the middle of next year.”
KEYTRUDA® (pembrolizumab) is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
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 (FDA) granted Fast Track designation to rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors with a TP53 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 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. In Phase 1, an overall response rate of
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. Our 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 over 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 our future plans or expectations for rezatapopt, including our ability to obtain approval as a treatment option on a tumor-agnostic basis and as a monotherapy or in combination with other agents, expectations regarding timing for interim data readouts and success of the Phase 2 portion of the PYNNACLE trial, our expectation and timing of NDA filing(s) with the FDA for the current clinical trial for rezatapopt, the current and future enrollment of patients in our clinical trials, the timing, progress and activation of sites for our clinical trials, and plans for MDACC and MSKCC’s investigator-initiated study assessing rezatapopt as monotherapy and in combination with azacitidine for treatment of recurrent or refractory AML/MDS 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 our product candidate development activities and planned clinical trials, our ability to execute on our 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 or expected results, our ability to fund operations, and the impact that a global pandemic, other public health emergencies or geopolitical tensions or conflicts may have on our clinical trials, supply chain, and operations, as well as those risks and uncertainties set forth in the section entitled “Risk Factors” in our Annual Report on Form 10-K, filed with the Securities and Exchange Commission (the “SEC”) on February 29, 2024, our Quarterly Report on Form 10-Q for the three months ended March 31, 2024, filed with the SEC on May 9, 2024, and our 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. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
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
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