Pipeline | Verastem, Inc.

Robust Clinical Program: Avutometinib in Multiple Combinations Across RAS/MAPK Pathway-Driven Tumors

Avutometinib, an oral RAF/MEK Clamp

Avutometinib is a RAF/MEK Clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF, potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition.

Defactinib, an oral, selective FAK Inhibitor

Defactinib is a best-in-class selective FAK inhibitor that has been studied as a monotherapy and in combination in patients with solid tumors.

Verastem-Sponsored Trials

Verastem Oncology’s pipeline is focused on RAS/MAPK-driven cancers, specifically novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and FAK inhibition.

Indication	Study Name	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
R/R LGSOC Regimen: avutometinib + defactinib vs investigator’s choice of treatments (ICT) Study Name: RAMP 301	RAMP 301	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
R/R LGSOC^1,2 Regimen: avutometinib +/- defactinib Study Name: RAMP 201	RAMP 201	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
R/R NSCLC (KRAS G12C) Regimen: avutometinib + sotorasib +/- defactinib Study Name: RAMP 203	RAMP 203	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
Pancreatic Ductal Adenocarcinoma Regimen: avutometinib + gemcitabine/nab-paclitaxel + defactinib Study Name: RAMP 205	RAMP 205	Discovery	Preclinical	Phase 1	Phase 2	Phase 3

Verastem Collaboration with GenFleet Therapeutics

Verastem Oncology entered into a collaboration agreement with GenFleet Therapeutics that includes three discovery programs and provides Verastem with exclusive options to license three compounds selected for collaboration after successful completion of pre-determined milestones in Phase 1 trials. The licenses would give Verastem Oncology development and commercialization rights outside of the GenFleet territories of mainland China, Hong Kong, Macau, and Taiwan.

Verastem has identified GFH375/VS-7375, a potential best-in-class, potent and selective oral KRAS G12D (ON/OFF) inhibitor, as the lead discovery program from the collaboration. GenFleet’s IND for GFH375/VS-7375 was approved in China in June 2024 and the Phase 1/2 trial in KRAS G12D-mutant solid tumors was subsequently initiated and the first patient was dosed in July 2024.

Indication	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
KRAS G12D-mutant Solid Tumors Regimen: Oral KRAS G12D (ON/OFF) Inhibitor GenFleet initiated Phase 1/2 trial in China.	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
Undisclosed	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
Undisclosed	Discovery	Preclinical	Phase 1	Phase 2	Phase 3

Investigator-Sponsored Trials

Indication	Study Name	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
R/R LGSOC Regimen: avutometinib + defactinib Study Name: IST-FRAME	IST-FRAME	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
Gynecological Cancers (RAS Pathway-driven)³ Regimen: avutometinib + defactinib Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
Mesonephric Regimen: avutometinib + defactinib Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
R/R NSCLC (KRAS mt) Regimen: avutometinib + everolimus (mTORi) Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
R/R Colorectal Cancer Regimen: avutometinib + cetuximab (EGFRi) Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3
ER+ Breast Cancer Regimen: avutometinib + abemaciclib + fulvestrant Study Name: IST	IST	Discovery	Preclinical	Phase 1	Phase 2	Phase 3

¹FDA Breakthrough Therapy Designation
²Registration-directed trial

These studies are investigating treatments or outcomes that have not received approval from a health authority. We are working diligently to demonstrate the safety and efficacy of these products, but there is no guarantee that the outcome of these studies will result in approval. We invite you to review our expanded access policy.

Investigator Sponsored Trials (IST)

We believe in the power of collaboration to help us push forward with new and promising cancer treatments. Our Verastem Oncology Investigator Sponsored Trial (IST) program strives to advance medical and scientific knowledge for our product candidates and disease states of interest. We welcome partnerships with researchers and sponsoring institutions that build on this mission.

Investigator Sponsored Trial Form

For additional details regarding our IST program or to submit a research request, please download, complete and submit the form below via email to verastem-IST@verastem.com.

Download Form

Research Collaborations

Verastem Oncology also accepts proposals for preclinical research collaborations. For more information, please reach out to us at research@verastem.com.