VS-7375 / Verastem, GenFleet Therap - LARVOL DELTA

Verastem Oncology Announces U.S. IND Clearance of VS-7375, Oral KRAS G12D (ON/OFF) Inhibitor, Enabling Phase 1/2a Trial in Advanced Solid Tumors (Businesswire) - "Verastem Oncology...announced the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application of VS-7375, an oral KRAS G12D (ON/OFF) inhibitor for clinical evaluation. The Company expects to initiate a Phase 1/2a study in mid-2025 with plans for multiple expansion cohorts, including combinations, in advanced solid tumors, such as pancreatic cancer, colorectal cancer, and non-small cell lung cancer. The Company also announced the acceptance of an abstract, by our partner GenFleet Therapeutics, for rapid oral presentation of the preliminary dose escalation phase of the Phase 1/2 study of VS-7375 (also known as GFH375) conducted by GenFleet at the upcoming 2025 American Society of Clinical Oncology (ASCO) Annual Meeting..."

IND • New P1/2 trial • P1/2 data • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

GFH375 (VS-7375): An oral, selective KRAS G12D (ON/OFF) inhibitor with potent anti-tumor efficacy as single agent and in combination with other anticancer therapies in preclinical models (AACR 2025) - P1/2 | "Furthermore, GFH375 was more potent than other KRAS G12D inhibitors (e.g. RMC-9805, MRTX1133) in reducing the level of RAF1-bound active KRAS G12D-GTP (ON) and inhibiting cell proliferation in MEFs expressing human KRAS G12D...Combination with the RAF/MEK clamp avutometinib also enhanced the anti-tumor efficacy of GFH375...Altogether, GFH375 is a potent and selective orally active inhibitor of KRAS G12D (ON/OFF) and demonstrated promising anti-tumor activity in multiple KRAS G12D tumor models in vivo as single agent and in combination with other anticancer therapies including cetuximab. These results support the ongoing clinical evaluation of GFH375 for treatment of patients with KRAS G12D mutant cancers (NCT06500676)."

Combination therapy • Preclinical • Colorectal Cancer • Endometrial Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

A Study of GFH375 in Patients With Advanced Solid Tumors With KRAS G12D Mutations (clinicaltrials.gov) - P1/2 | N=390 | Recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | N=290 ➔ 390

Enrollment change • Oncology • Solid Tumor • KRAS

GFH375 (VS-7375): An oral, selective KRAS G12D (ON/OFF) inhibitor with potent anti-tumor efficacy as single agent and in combination with other anticancer therapies in preclinical models (Businesswire) - "Verastem Oncology announces multiple presentations focused on RAS/MAPK pathway inhibition at AACR Annual Meeting 2025....Abstract #: 4394....VS-7375 (GFH375), a selective oral KRAS G12D (ON/OFF) inhibitor, was found to be more potent than other KRAS G12D inhibitors in preclinical models. In addition, the combination of VS-7375 with the anti-EGFR antibody, cetuximab, induced strong tumor regressions in preclinical models, including complete responses in all mice in a colorectal cancer model."

Preclinical • Colorectal Cancer

VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in Advanced Solid Tumors (Businesswire) - "Verastem filed an investigational new drug (IND) application in the U.S. for VS-7375 in the first quarter of 2025. Key Milestones Expected for 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."

IND • New P1/2 trial • P1 data • Non Small Cell Lung Cancer • Pancreatic Cancer

VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in Advanced Solid Tumors (Businesswire) - "Share preclinical and clinical data from the Phase 1 study of VS-7375 in China in H1 2025."

P1 data • Preclinical • Solid Tumor

Verastem anticipates filing a U.S. IND application for VS-7375 during Q1 2025… (Businesswire) - 'Verastem remains on track to file a U.S. investigational new drug (IND) application for VS-7375 during the first quarter of 2025 and expects to initiate a Phase 1/2a study in mid-2025. The Companies expect to share updated preclinical and clinical data at upcoming medical meetings in mid-2025."

IND • New P1/2 trial • Oncology

Verastem Oncology Exercises Option Early to License VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, from GenFleet Therapeutics and Provides Preliminary Clinical Update on Phase 1 Study in China (Businesswire) - P1/2 | N=290 | NCT06500676 | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | "Verastem Oncology...announced it has exercised early the option to license from GenFleet Therapeutics VS-7375 (also known as GFH375), a potential best-in-class oral and selective KRAS G12D (ON/OFF) inhibitor. In addition, the Company announced preliminary clinical data from the Phase 1 study being conducted by GenFleet in China....As previously announced by GenFleet, 26 patients have been treated with VS-7375 in a Phase 1 dose-escalation study being conducted in China. Both confirmed and unconfirmed partial responses have been observed, including patients with metastatic pancreatic cancer and advanced non-small cell lung cancer. In addition, six dose cohorts have been cleared with no dose-limiting toxicities (DLTs) observed."

Licensing / partnership • P1 data • Non Small Cell Lung Cancer • Pancreatic Cancer • Solid Tumor

Verastem Oncology Reports Second Quarter 2024 Financial Results and Highlights Recent Business Updates (Businesswire) - "Avutometinib and Defactinib Combination in First-Line Metastatic Pancreatic Cancer; Expect to report updated data from the ongoing RAMP 205 trial in Q1 2025; GFH375 (VS-7375): Oral KRAS G12D (ON/OFF) Inhibitor: Plan to initiate development studies outside of China after evaluating initial dose escalation data from the Phase 1 study of GFH375 (VS-7375) in China to accelerate a path forward in the U.S. and rest of world."

New trial • P1/2 data • Pancreatic Cancer

A Study of GFH375 in Patients With Advanced Solid Tumors With KRAS G12D Mutations (clinicaltrials.gov) - P1/2 | N=290 | Recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor • KRAS

A Study of GFH375 in Patients With Advanced Solid Tumors With KRAS G12D Mutations (clinicaltrials.gov) - P1/2 | N=290 | Not yet recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc.

Metastases • New P1/2 trial • Oncology • Solid Tumor • KRAS

Verastem Oncology Announces First Patient Dosed with GFH375/VS-7375, a KRAS G12D (ON/OFF) Inhibitor, in a Phase 1/2 Trial in China as Part of Collaboration with GenFleet Therapeutics (Businesswire) - "Verastem plans to initiate development studies outside of China after evaluating initial dose escalation data from the Phase 1 study in China....Verastem Oncology...announced that the first patient has been dosed in a Phase 1/2 trial in China, conducted by GenFleet Therapeutics, evaluating GFH375/VS-7375, a KRAS G12D (ON/OFF) inhibitor."

Trial status • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

GenFleet Receives IND Approval from China's NMPA for GFH375, an Oral KRAS G12D (ON/OFF) Inhibitor, in a Phase I/II Clinical Trial Treating Advanced Solid Tumor Patients with KRAS G12D Mutation (PRNewswire) - "GenFleet Therapeutics...announced China's National Medical Products Administration (NMPA) has approved the clinical trial application for GFH375 (VS-7375) in an open-label, multi-center phase I/II study targeting advanced solid tumor patients with KRAS G12D mutation....The study (GFH375X1101) will be conducted at ~40 hospitals, including the prominent Shanghai Chest Hospital. In phase I, the study aims to evaluate the safety/tolerability and preliminary efficacy of GFH375 in advanced G12D-mutant solid tumor patients....Progressing into Phase II, the study will further assess the efficacy of GFH375 for patients of advanced solid tumors including pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and non-small cell lung cancer (NSCLC) – three cancer types with highest prevalence of G12D mutation; the study will also investigate the underlying mechanisms of patients' response and resistance to the treatment."

New P1/2 trial • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

GFH375 (VS-7375): An oral, selective KRAS G12D (ON/OFF) inhibitor with potent anti-tumor efficacy (AACR 2024) - "Background: KRAS is the best-known oncogene but had long been considered 'undruggable' until the approval of the first KRAS G12C inhibitor sotorasib in 2021. GFH375 is a highly potent and selective orally active inhibitor of KRAS G12D (ON/OFF) and demonstrated promising anti-tumor activity in multiple KRAS G12D tumor models. GFH375 was also effective in an intracranial tumor model. GFH375 showed strong synergy with avutometinib in vitro and in vivo."

Clinical • Oncology • BRAF • HRAS • KRAS • NRAS

GenFleet Therapeutics Announces Potent Anti-tumor Efficacy of GFH375, an Oral KRAS G12D (ON/OFF) Inhibitor, and its Potential in Combination Therapy with RAF/MEK Clamp at 2024 AACR Annual Meeting (PRNewswire) - "GenFleet Therapeutics...unveiled the latest research findings of GFH375, an oral KRAS G12D (ON/OFF) inhibitor, at the poster presentation of the 2024 American Association for Cancer Research (AACR) Annual Meeting....GFH375 induces tumor regression in multiple KRAS G12D CDX tumor models via oral administration. It also demonstrates potent anti-tumor activity in an intracranial CDX tumor model, which suggests the potential of GFH375 as a treatment for KRAS G12D mutant cancers with brain metastases....The combination of GFH375 and avutometinib enhances anti-tumor efficacy and leads to more significant tumor regression over either drug candidate alone. Meanwhile, the results exhibit favorable toxicity profile of this combination."

Preclinical • Oncology • Solid Tumor

Verastem Oncology Announces Preclinical Presentations for New Oral G12D Inhibitor and for Avutometinib and Defactinib Combination as a Backbone of Therapy for RAS/MAPK Driven Cancers at AACR Annual Meeting 2024 (Businesswire) - "Verastem Oncology...announced that preclinical data will be presented in five posters at the American Association for Cancer Research (AACR) Annual Meeting 2024....The presentations will highlight anti-tumor efficacy of GFH375 (VS-7375), a potent and selective orally bioavailable KRAS G12D (ON/OFF) inhibitor, and will also show data of RAF/MEK clamp plus FAK inhibition in pancreatic ductal adenocarcinoma (PDAC) models supporting the ongoing RAMP 205 trial. Additional presentations will support the use of avutometinib and FAK inhibitor combination in cutaneous melanoma models to overcome resistance to BRAF and MEK inhibitors, resistance to immunotherapy, and brain metastasis....'We look forward to an IND submission by GenFleet in China in H1 2024'."

New P1 trial • Preclinical • Melanoma • Pancreatic Ductal Adenocarcinoma

Verastem Oncology Outlines Key 2024 Strategic Priorities and Upcoming Catalysts for Advancing Avutometinib and Defactinib and Broader Pipeline in RAS Pathway-Driven Cancers (Businesswire) - "GenFleet expected to...begin a Phase 1 trial for GFH375/VS-7375 in China in H2 2024; Companies to continue discovery/lead optimization for second and third programs."

Commercial • New P1 trial • Oncology • Solid Tumor

Verastem Oncology Selects Oral KRAS G12D Inhibitor GFH375/VS-7375 as Lead Program in Discovery and Development Collaboration with GenFleet Therapeutics (Businesswire) - "Verastem Oncology...announced a potential best-in-class KRAS G12D oral inhibitor as the lead program of its discovery and development collaboration with GenFleet Therapeutics ('GenFleet')....'The GLP toxicology studies are complete and we look forward to GenFleet’s anticipated filing of the IND for this KRAS G12D inhibitor in the first half of 2024'."

IND • New molecule • Oncology