Pipeline | Verastem, Inc.

At Verastem, we are pursuing unexplored avenues in the RAS/MAPK pathway with 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. We are exploring both monotherapy and synergistic combinations with our current
pipeline and external assets. Our pipeline includes:

Avutometinib, an oral RAF/MEK clamp: we are evaluating avutometinib in multiple combination studies in low-grade serous ovarian cancer (LGSOC), pancreatic ductal adenocarcinoma (PDAC), and other RAS/MAPK-driven tumors.
defactinib, an oral FAK inhibitor: we are evaluating defactinib in combination with avutometinib and other external assets in low-grade serous ovarian cancer, pancreatic cancer, and other RAS/MAPK-driven tumors.
VS-7375, an oral KRAS G12D (ON/OFF) inhibitor: we are evaluating VS-7375 as monotherapy and in combinations for KRAS G12D-mutated PDAC, non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and other solid tumors.
Undisclosed RAS Pathway-related targets: from our collaboration with GenFleet Therapeutics, Verastem has two undisclosed assets at discovery phase targeting RAS/MAPK pathway-driven cancers.

Avutometinib, RAF/MEK Clamp + Defactinib, FAKi

Indication	Study Name	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
Recurrent LGSOC¹ Regimen: avutometinib + defactinib Study Name: RAMP 201	RAMP 201	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
Recurrent LGSOC Regimen: international confirmatory trial of avutometinib + defactinib vs investigator’s choice of treatments (ICT) Study Name: RAMP 301	RAMP 301	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
PDAC Regimen: avutometinib + defactinib + gemcitabine/nab-paclitaxel Study Name: RAMP 205	RAMP 205	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved

¹ FDA Accelerated Approval, May 8, 2025

VS-7375, Oral KRAS G12D (ON/OFF) Inhibitor

Indication	Study Name	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
KRAS G12D-mutated solid tumors (PDAC, NSCLC, CRC) Regimen: dose escalation and expansion trial of VS-7375 monotherapy + various combinations Study Name: TARGET-D 101	TARGET-D 101	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
KRAS G12D-mutated 2L metastatic PDAC Regimen: registration-directed trial of VS-7375 monotherapy + EGFR combination Study Name: TARGET-D 201	TARGET-D 201	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
KRAS G12D-mutated 2L/3L advanced NSCLC Regimen: registration-directed trial of VS-7375 monotherapy Study Name: TARGET-D 202	TARGET-D 202	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved
KRAS G12D-mutated 2L+ metastatic CRC Regimen: registration-directed trial of VS-7375 combinations with EGFR and chemotherapy Study Name: TARGET-D 203	TARGET-D 203	Discovery	Preclinical	Phase 1	Phase 2	Phase 3	FDA Approved

Verastem Collaboration with GenFleet Therapeutics

Verastem Oncology entered into a collaboration agreement with GenFleet Therapeutics for three discovery programs, with exclusive options to license three compounds upon successful completion of predetermined Phase 1 milestones. These licenses would grant Verastem development and commercialization rights outside of GenFleet territories (mainland China, Hong Kong, Macau, and Taiwan).

VS-7375 (known as GFH375 in China), a potential best-in-class, potent and selective oral KRAS G12D (ON/OFF) inhibitor, has been identified as the lead discovery program. GenFleet’s IND for GFH375 (VS-7375) was approved in June 2024, and they are currently conducting Phase 1/2 and Phase 3 clinical trials in China.

Investigator-Sponsored Trials

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.

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

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 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.