Verastem Oncology Outlines 2025 Strategic Priorities and Milestones for Novel Pipeline Targeting RAS/MAPK Pathway-Driven Cancers
Verastem Oncology announced key 2025 priorities and milestones for its RAS/MAPK pathway-driven cancer pipeline. The FDA granted priority review for avutometinib plus defactinib combination therapy for recurrent KRAS mutant LGSOC, with a PDUFA date of June 30, 2025. The company plans a U.S. commercial launch in mid-2025.
Key developments include: ongoing RAMP 205 trial in metastatic pancreatic cancer with updated data expected in Q1 2025; VS-7375 IND filing planned for Q1 2025 with Phase 1/2a study initiation in mid-2025; and recent financing providing runway beyond potential FDA approval.
The company's 2025 strategic priorities focus on: launching avutometinib plus defactinib in the U.S. for LGSOC; expanding the combination therapy to other solid tumors; and advancing its early-stage pipeline, including VS-7375, a KRAS G12D inhibitor.
Verastem Oncology ha annunciato le principali priorità e traguardi per il 2025 riguardanti il suo programma oncologico basato sulla via RAS/MAPK. La FDA ha concesso la revisione prioritaria per la terapia combinata di avutometinib e defactinib per il LGSOC ricorrente con mutazione KRAS, con una data PDUFA fissata al 30 giugno 2025. L'azienda prevede un lancio commerciale negli Stati Uniti a metà del 2025.
Gli sviluppi chiave includono: il trial RAMP 205 in corso sul cancro pancreas metastatico con dati aggiornati previsti per il primo trimestre del 2025; la registrazione dell'IND per VS-7375 programmata per il primo trimestre del 2025 con inizio dello studio di fase 1/2a a metà 2025; e un recente finanziamento che fornisce una durata oltre la potenziale approvazione della FDA.
Le priorità strategiche del 2025 dell'azienda si concentrano su: il lancio di avutometinib e defactinib negli Stati Uniti per il LGSOC; l'espansione della terapia combinata ad altri tumori solidi; e il progresso della sua pipeline in fase iniziale, incluso VS-7375, un inibitore di KRAS G12D.
Verastem Oncology anunció las principales prioridades y hitos para 2025 en su cartera de tratamientos contra el cáncer impulsada por la vía RAS/MAPK. La FDA otorgó revisión prioritaria para la terapia combinada de avutometinib y defactinib para LGSOC recurrente con mutación KRAS, con una fecha PDUFA del 30 de junio de 2025. La empresa planea un lanzamiento comercial en EE. UU. a mediados de 2025.
Los desarrollos clave incluyen: el ensayo RAMP 205 en curso en cáncer de páncreas metastásico con datos actualizados esperados para el primer trimestre de 2025; la presentación de IND para VS-7375 planeada para el primer trimestre de 2025 con el inicio del estudio de fase 1/2a a mediados de 2025; y un reciente financiamiento que proporciona recursos más allá de una posible aprobación de la FDA.
Las prioridades estratégicas de la compañía para 2025 se centran en: el lanzamiento de avutometinib y defactinib en EE. UU. para LGSOC; la expansión de la terapia combinada a otros tumores sólidos; y el avance de su pipeline en etapa temprana, incluido VS-7375, un inhibidor de KRAS G12D.
Verastem Oncology는 RAS/MAPK 경로 기반 암 파이프라인에 대한 2025년 주요 우선事项 및 이정표를 발표했습니다. FDA는 재발성 KRAS 돌연변이 LGSOC에 대한 avutometinib과 defactinib 조합 요법에 대해 우선 심사를 승인했으며, PDUFA 날짜는 2025년 6월 30일입니다. 회사는 2025년 중반 미국에서 상용화를 계획하고 있습니다.
주요 개발 사항에는: 1분기에 업데이트된 데이터가 예상되는 전이성 췌장암에 대한 RAMP 205 시험 진행; 2025년 1분기에 VS-7375 IND 제출이 계획되어 있으며, 2025년 중반에 1/2a 단계 연구가 시작될 예정; 그리고 최근 자금 조달이 FDA 승인 가능성을 넘어서는 자원을 제공하고 있습니다.
회사의 2025년 전략적 우선사항은: LGSOC를 위한 미국에서의 avutometinib과 defactinib 출시; 조합 요법을 다른 고형 종양으로 확대; 그리고 KRAS G12D 억제제인 VS-7375를 포함한 초기 단계 파이프라인을 발전시키는 데 초점을 맞추고 있습니다.
Verastem Oncology a annoncé ses priorités et objectifs clés pour 2025 concernant son pipeline de thérapies contre le cancer basé sur la voie RAS/MAPK. La FDA a accordé un examen prioritaire pour la thérapie combinée d'avutometinib et de defactinib pour le LGSOC récurrent avec mutation KRAS, avec une date PDUFA fixée au 30 juin 2025. L'entreprise prévoit un lancement commercial aux États-Unis à la mi-2025.
Les développements clés incluent : l'essai RAMP 205 en cours sur le cancer du pancréas métastatique avec des données mises à jour attendues au premier trimestre 2025 ; dépôt de demande IND pour VS-7375 prévu pour le premier trimestre 2025 avec le début de l'étude de phase 1/2a à la mi-2025 ; et un récent financement fournissant des fonds suffisants au-delà d'une éventuelle approbation de la FDA.
Les priorités stratégiques de l'entreprise pour 2025 se concentrent sur : le lancement d'avutometinib et de defactinib aux États-Unis pour le LGSOC ; l'expansion de la thérapie combinée à d'autres tumeurs solides ; et l'avancement de son pipeline précoce, y compris VS-7375, un inhibiteur de KRAS G12D.
Verastem Oncology hat die wichtigsten Prioritäten und Meilensteine für 2025 für seine krebserzeugende Pipeline, die auf dem RAS/MAPK-Weg basiert, bekannt gegeben. Die FDA hat die priorisierte Prüfung für die Kombinationstherapie aus avutometinib und defactinib bei wiederkehrendem KRAS-mutiertem LGSOC genehmigt, mit einem PDUFA-Datum vom 30. Juni 2025. Das Unternehmen plant einen kommerziellen Markteintritt in den USA Mitte 2025.
Wichtige Entwicklungen umfassen: den laufenden RAMP 205-Test bei metastasiertem Bauchspeicheldrüsenkrebs, bei dem im ersten Quartal 2025 aktualisierte Daten erwartet werden; geplante IND-Einreichung für VS-7375 im ersten Quartal 2025 mit Beginn der Phase 1/2a-Studie Mitte 2025; und die kürzliche Finanzierung, die Spielraum über die potenzielle FDA-Zulassung hinaus bietet.
Die strategischen Prioritäten des Unternehmens für 2025 konzentrieren sich auf: die Einführung von avutometinib und defactinib in den USA für LGSOC; die Erweiterung der Kombinationstherapie auf andere solide Tumoren; und die Weiterentwicklung seiner frühen Pipeline, einschließlich VS-7375, einem KRAS G12D-Inhibitor.
- FDA granted Priority Review for avutometinib plus defactinib with PDUFA date set for June 30, 2025
- Recent debt and equity financing strengthens cash position beyond FDA approval
- Strategic collaboration with IQVIA for commercialization support
- 83% overall response rate (5/6 patients) in RAMP 205 trial dose level 1 cohort
- VS-7375 showed partial responses in pancreatic and lung cancers with no dose-limiting toxicities
- Accelerated approval pathway requires additional confirmatory trials
- Commercial launch dependent on FDA approval
- Small patient sample size in RAMP 205 trial preliminary results
Insights
Verastem's 2025 strategic roadmap presents multiple value-driving catalysts that could transform the company from clinical to commercial stage. The priority review designation for avutometinib plus defactinib in KRAS-mutant LGSOC significantly accelerates their path to market, with the June 30, 2025 PDUFA date representing a critical inflection point.
The LGSOC opportunity, while targeting a rare indication, represents a strategic entry point with competition and high unmet need. The combination therapy showed compelling efficacy in the RAMP 201 trial and the planned publication of primary analysis data in H1 2025 could strengthen its position for NCCN guidelines inclusion, important for market adoption.
The company's pipeline diversification strategy is particularly noteworthy. The RAMP 205 trial in first-line metastatic pancreatic cancer, showing an 83% overall response rate in initial cohorts, could open a significantly larger market opportunity. The recent VS-7375 acquisition targeting KRAS G12D mutations is strategically important, as G12D represents approximately 30% of all KRAS mutations in pancreatic cancer.
Financially, the Oberland Capital agreements provide important runway beyond potential FDA approval, while the IQVIA partnership brings commercial infrastructure support, reducing execution risk for the LGSOC launch. The multiple data readouts scheduled throughout 2025 across different programs create a steady stream of potential value-creating events.
The therapeutic strategy of combining RAF/MEK and FAK inhibition represents an innovative approach to addressing resistance mechanisms in RAS-driven cancers. The priority review in LGSOC validates this scientific rationale, while the expansion into pancreatic cancer and NSCLC demonstrates the platform's broader potential.
The RAMP 205 trial data in pancreatic cancer is particularly intriguing, as the 83% response rate in first-line treatment significantly exceeds historical benchmarks with standard chemotherapy. The planned RP2D decision in H1 2025 will be important for determining the optimal dosing strategy for expansion cohorts.
The VS-7375 program targeting KRAS G12D introduces a potentially best-in-class approach using an ON/OFF inhibitor mechanism. This differs from traditional KRAS inhibitors by potentially achieving better target engagement while maintaining a favorable safety profile, as evidenced by the absence of dose-limiting toxicities across six dose levels in initial clinical testing.
The multi-pronged development strategy across LGSOC, pancreatic cancer and NSCLC, combined with the novel KRAS G12D program, positions Verastem to potentially address multiple areas of high unmet need in RAS pathway-driven cancers.
Avutometinib plus defactinib granted priority review by FDA, under the accelerated approval pathway, for recurrent KRAS mutant LGSOC; PDUFA action date set for June 30, 2025
Potential
RAMP 205 trial in 1L metastatic pancreatic cancer continues to progress, with updated data expected in Q1 2025 to guide RP2D decision for trial expansion
VS-7375 is on track for
Cash position following recent debt and equity financing provides expected runway beyond potential FDA approval and helps to advance early-stage pipeline
"We ended 2024 having made tremendous progress across our pipeline programs, including FDA acceptance of our NDA with Priority Review for avutometinib plus defactinib in recurrent KRAS mutant low-grade serous ovarian cancer. As we head into 2025, we are building on the foundational milestones achieved in 2024 and are poised for a transformative year of growth as we evolve into a commercial-stage company while advancing several clinical programs,” said Dan Paterson, president and chief executive officer at Verastem Oncology. “With the addition of VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, we are well-positioned to further establish our leadership in targeting RAS/MAPK pathway-driven cancers, including metastatic pancreatic cancer, non-small cell lung cancer, and KRAS G12D mutant solid tumors.”
In 2025, Verastem will focus on three strategic priorities to drive sustainable long-term growth:
-
Successfully launch avutometinib plus defactinib in recurrent KRAS mutant low-grade serous ovarian cancer (LGSOC) in the
U.S. and continue to advance the regulatory pathway inJapan andEurope - Maximize the synergistic potential of the avutometinib plus defactinib combination in other advanced solid tumors for market expansion opportunities
- Advance its novel, early-stage pipeline, including its potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, to create multiple opportunities to demonstrate transformative outcomes for people living with RAS/MAPK pathway-driven cancers
Successfully Launch Avutometinib Plus Defactinib in the
On December 30, 2024, the
To further strengthen its positioning for a potential mid-2025 launch, Verastem previously announced agreements with Oberland Capital and IQVIA. The agreements with Oberland Capital include a debt refinancing and an equity investment, which strengthens the Company’s cash position and will help fund commercialization past FDA approval and other pipeline programs. The strategic collaboration with IQVIA leverages IQVIA’s world-class infrastructure and commercialization solutions to complement the Company’s launch strategy in recurrent LGSOC.
Key Milestones Expected for 2025:
- Primary analysis from both the FRAME and RAMP 201 clinical trials will be published in H1 2025; submit RAMP 201 primary analysis publication for NCCN consideration in H1 2025.
- Present additional analyses from the RAMP 201 trial at a medical meeting in Q1 2025.
- Plan for FDA decision on approval of the combination of avutometinib plus defactinib in recurrent KRAS mutant LGSOC, expected by June 30, 2025.
- Complete enrollment for the international Phase 3 confirmatory RAMP 301 clinical trial for patients with recurrent LGSOC regardless of KRAS mutation status by the end of 2025.
-
Report initial data from the RAMP 201J Phase 2 clinical trial being conducted in
Japan with the Japanese Gynecologic Oncology Group (JGOG) evaluating the safety and efficacy of avutometinib in combination with defactinib for recurrent LGSOC in H2 2025. -
Continue to advance the regulatory pathway in
Japan andEurope .
Maximize the Synergistic Potential of Avutometinib Plus Defactinib for Advanced Solid Tumor Market Expansion Opportunities
RAMP 205: Avutometinib Plus Defactinib in Combination with Chemotherapy in First-Line Metastatic Pancreatic Cancer
At the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2024, Verastem presented initial interim data from the ongoing RAMP 205 Phase 1/2 clinical trial evaluating multiple dose cohorts of avutometinib plus defactinib in combination with gemcitabine and Nab-paclitaxel as first-line systemic treatment for patients with metastatic pancreatic cancer. Patients receiving the combination in the dose level 1 cohort achieved a confirmed overall response rate (ORR) of
Key Milestones Expected for 2025:
- Report updated data from the ongoing RAMP 205 trial in Q1 2025 and present data at a medical meeting in mid-year 2025.
- Choose a Recommended Phase 2 Dose (RP2D) for trial expansion in H1 2025.
RAMP 203: Avutometinib Plus Defactinib in Combination with a KRAS G12C Inhibitor in Non-Small Cell Lung Cancer (NSCLC)
In December 2024, the Company announced preliminary clinical data for the triplet combination cohort of avutometinib and LUMAKRAS™ (sotorasib) plus defactinib in the RAMP 203 Phase 1/2 study in KRAS G12C mutant advanced NSCLC. No DLTs have been observed in the triplet combination.
Key Milestones Expected for 2025:
- Complete enrollment in the KRAS G12C inhibitor, prior-treated Stage 1 Part B cohort in Q1 2025. Continue to follow patients in both doublet cohorts (KRAS G12C inhibitor naïve and prior-treated) for safety and efficacy to determine if observed efficacy supports expanded enrollment.
- Complete enrollment and evaluate the safety and efficacy of the triplet combination in H1 2025.
- Present an interim update at a medical meeting in H2 2025.
Advance Novel, Early-stage Pipeline to Create Multiple Opportunities to Demonstrate Potentially Transformative Outcomes in RAS/MAPK Pathway-driven Cancers
VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in Advanced Solid Tumors
In July 2024, GenFleet Therapeutics began dosing several patients in a Phase 1/2 trial in
Key Milestones Expected for 2025:
-
File an investigational new drug (IND) application in the
U.S. for VS-7375 in Q1 2025. -
Initiate a Phase 1/2a trial in the
U.S. by mid-2025. -
Share preclinical and clinical data from the Phase 1 study of VS-7375 in
China in H1 2025.
Discovery/lead optimization continues for the second and third programs in the GenFleet collaboration.
About the Avutometinib and Defactinib Combination
Avutometinib is an oral RAF/MEK clamp that potentially inhibits MEK1/2 kinase activities and induces inactive complexes of MEK with ARAF, BRAF, and CRAF, potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of the MEK-only inhibitors.
Defactinib is an oral, selective inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2), the two members of the focal adhesion kinase family of non-receptor protein tyrosine kinases. FAK and Pyk2 integrate signals from integrin and growth factor receptors to regulate cell proliferation, survival, migration, and invasion. FAK activation has been shown to mediate resistance to multiple anti-cancer agents, including RAF and MEK inhibitors.
Verastem Oncology is currently conducting clinical trials with avutometinib with and without defactinib in RAS/MAPK-driven tumors as part of its Raf And Mek Program or RAMP. Verastem is currently enrolling patients and activating sites for RAMP 301 (GOG-3097/ENGOT-ov81/NCRI) (NCT06072781), an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC).
Verastem was granted Priority Review and a Prescription Drug User Fee Act (PDUFA) date of June 30, 2025, for its New Drug Application (NDA) to the
Verastem Oncology has established a clinical collaboration with Amgen to evaluate LUMAKRAS™ (sotorasib) in combination with avutometinib and defactinib in both treatment-naïve patients and in patients whose KRAS G12C mutant non-small cell lung cancer progressed on a G12C inhibitor as part of the RAMP 203 trial (NCT05074810). Verastem has received Fast Track Designation from the FDA for the triplet combination in April 2024. RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award. FDA granted Orphan Drug Designation to the avutometinib and defactinib combination for the treatment of pancreatic cancer.
About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor
VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. GenFleet’s IND for VS-7375 (known as GFH375 in
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a late-stage development biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with RAS/MAPK pathway-driven cancers. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition and KRAS G12D inhibition. For more information, please visit www.verastem.com and follow us on LinkedIn.
Forward-Looking Statements
This press release includes forward-looking statements. These forward-looking statements generally can be identified by the use of words such as “anticipate,” “expect,” “plan,” “could,” “may,” “believe,” “estimate,” “forecast,” “goal,” “project,” and other words of similar meaning. Such forward-looking statements address various matters about, among other things, Verastem Oncology’s programs and product candidates, strategy, future plans and prospects, including statements related to the potential for and timing of commercialization of product candidates, the anticipated timing for the IND application for VS-7375/GFH375, the expected outcome and benefits of the Company’s collaboration with GenFleet Therapeutics (
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For Investor and Media Inquiries:
Julissa Viana
Vice President, Corporate Communications and Investor Relations
investors@verastem.com or
media@verastem.com
Source: Verastem Oncology
FAQ
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