VS-7375 / Verastem, GenFleet Therap - LARVOL DELTA

A first-in-human phase I/II study of GFH375, a highly selective and potent oral KRAS G12D inhibitor in patients with KRAS G12D mutant advanced solid tumors. (ASCO 2025) - P1/2 | "According to the preliminary data from ongoing FIH study, GFH375 monotherapy has demonstrated good tolerability and promising anti-tumor activities in pts with advanced solid tumor supporting further clinical development."

Clinical • Metastases • P1/2 data • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Solid Tumor • KRAS

Efficacy and safety of GFH375 monotherapy in previously treated advanced KRAS G12D-mutant pancreatic ductal adenocarcinoma (PDAC) (ESMO 2025) - P1/2 | "Conclusions GFH375 monotherapy shows promising efficacy with a manageable safety profile in previously treated KRAS G12D-mutant PDAC. The trial is still ongoing."

Clinical • Late-breaking abstract • Metastases • Monotherapy • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CDKN2A • KRAS • SMAD4 • TP53

RCZY-869: A highly potent, selective, and orally bioavailable covalent KRASG12D (ON-state) inhibitor with robust antitumor activity in preclinical models of KRASG12D-driven solid tumors (AACR 2026) - "Phase 1/1b data show ON-state inhibitor RMC-9805 and ON/OFF inhibitor VS-7375 (GFH375) have comparable objective response rates (ORR) and disease control rates (DCR) in NSCLC at their respective recommended Phase 2 doses (RP2D). These findings position RCZY-869 as a novel ON-state-selective KRASG12D inhibitor with compelling preclinical potency and efficacy. Ongoing characterization advances its candidate package to support clinical development."

Preclinical • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

VS-7375: An oral, selective KRAS G12D dual ON/OFF inhibitor with potent anti-tumor activity as a single agent and in combination with other agents (AACR 2026) - P1/2 | "To assess potential benefits of dual ON/OFF inhibition relative to ON-only RAS inhibitors, we compared efficacy in KRAS G12D mt in vivo models relative to the KRAS G12D ON-only inhibitor zoldonrasib (RMC-9805) and the pan-RAS ON-only inhibitor daraxonrasib (RMC-6236). Lastly, addition of a FAK inhibitor with VS-7375 increased duration of tumor regression in KRAS G12D mt cancer models, altogether supporting the potential clinical evaluation of novel combination strategies with VS-7375 in patients with KRAS G12D mt cancers for maximal anti-tumor efficacy and durability. VS-7375 is currently in phase 1/2 clinical evaluation in the US (VS-7375-101; NCT07020221) and in advanced clinical evaluation in China (NCT06500676) as monotherapy and in combination with cetuximab or chemotherapy ± pembrolizumab for patients with KRAS G12D mt cancers."

Combination therapy • Colorectal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • MTAP

VS-7375, a non-covalent dual ON/OFF KRASG12D inhibitor, displays superior activity to ON-only KRASG12D inhibitors in preclinical models of pancreatic cancer (AACR 2026) - "Abstract is embargoed at this time."

Late-breaking abstract • Preclinical • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Strong durable tumor regressions with the KRASG12D ON/OFF inhibitor VS-7375 in combination with PRMT5 inhibition in MTAP-deleted/KRASG12D-mutant pancreatic cancer (AACR 2026) - "Abstract is embargoed at this time."

Combination therapy • Late-breaking abstract • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • MTAP

Late-Breaking Abstracts (Verastem Press Release) - "Late-breaking abstracts will be available on the AACR Annual Meeting website on April 17, 2026....Abstract #: LB183 / 5; Title: Strong durable tumor regressions with the KRAS G12D ON/OFF inhibitor VS-7375 in combination with PRMT5 inhibition in MTAP-deleted/KRAS G12D-mutant pancreatic cancer....Abstract #: LB197 / 19; Title: VS-7375, a non-covalent dual ON/OFF KRAS G12D inhibitor, displays superior activity to ON-only KRAS G12D inhibitors in preclinical models of pancreatic cancer."

Late-breaking abstract • Preclinical • Pancreatic Cancer

Title: VS-7375: An oral, selective KRAS G12D dual ON/OFF inhibitor with potent anti-tumor activity as a single agent and in combination with other agents (Verastem Press Release) - "Abstracts Accepted for Presentation at the AACR Annual Meeting 2026....In the KP4 KRAS G12D pancreatic cancer model, VS-7375 (50 mg/kg twice daily), zoldonrasib (100 mg/kg once daily) and daraxonrasib (25 mg/kg once daily), produced similar initial tumor regression through day nine. By approximately day 20, however, zoldonrasib and daraxonrasib lost anti-tumor activity with tumor outgrowth, (mean tumor volume >850 mm by day 30) whereas VS-7375 maintained sustained tumor regression (mean tumor volume ~80 mm by day 30), consistent with pharmacodynamic analyses showing durable pathway inhibition only with VS-7375....VS-7375 also showed deeper tumor regression compared to these RAS ON-only inhibitors in KRAS G12D-mutated lung and colorectal xenograft models."

Preclinical • Colorectal Cancer • Non Small Cell Lung Cancer

VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor in Advanced Solid Tumors (Businesswire) - "The Company today announced an update on its progress with the VS-7375-101 Phase 1/2 study....The 600 mg QD dose level of VS-7375 in combination with cetuximab was cleared with no DLTs and higher doses are now being evaluated....As of the January 30, 2026 data cutoff, VS-7375 demonstrated an encouraging safety profile and was generally well-tolerated across all monotherapy dose levels evaluated to date. Patients (n=23) receiving VS-7375 at either 400 mg QD, 600 mg QD or 900 mg QD with a mean duration of therapy of 1.6 months (0.7-5.6), reported no drug related liver function test abnormalities."

P1/2 data • Trial status • Solid Tumor

GenFleet’s KRAS G12D inhibitor GFH375 secured China’s Breakthrough Therapy Designation for previously treated NSCLC patients. (TipRanks)

Breakthrough therapy • Non Small Cell Lung Cancer

A Phase 1/2a Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors (clinicaltrials.gov) - P1/2 | N=295 | Recruiting | Sponsor: Verastem, Inc. | Trial completion date: Sep 2028 ➔ Dec 2028 | Trial primary completion date: Sep 2028 ➔ Dec 2028

Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

VS-7375:…The combination dose escalation cohorts were initiated in first-line (1L) NSCLC and 2L PDAC at the end of 2025 (Businesswire)

Trial status • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

2026 Priorities:…VS-7375 (Businesswire) - "Verastem expects to: (i) Report an interim update on the Phase 1/2 trial of VS-7375 in 1H 2026; (ii) Select the recommended Phase 2 dose (RP2D) with cetuximab and initiate the CRC combination expansion cohort in 1H 2026; (iii) Engage with the FDA in 1H 2026 to discuss its development path forward, including potential registration-directed clinical trials in PDAC, NSCLC, and CRC; (iv) Complete enrollment in combination dose-escalation cohorts in mid-2026; (v) Complete enrollment in monotherapy expansion cohorts in 2H 2026; (vi) Select the RP2D and plan to initiate the PDAC and NSCLC combination expansion cohorts in 2H 2026."

FDA event • P1/2 data • Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

A Study of GFH375 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors Harboring KRAS G12D Mutation (clinicaltrials.gov) - P1/2 | N=126 | Recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc.

New P1/2 trial • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Phase III Study to Compare GFH375 and Chemotherapy in Patients With KRAS G12D-Mutant Metastatic Pancreatic Cancer (clinicaltrials.gov) - P3 | N=320 | Not yet recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc.

Monotherapy • New P3 trial • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

GFH375X1201: A Phase II Study to Evaluate GFH375 in Patients With KRAS G12D Mutant Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | N=83 ➔ 0 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Dec 2027 ➔ Aug 2027

Enrollment change • Monotherapy • Trial primary completion date • Trial withdrawal • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Key Milestones (Businesswire) - "Plan to initiate the dose escalation cohorts in combination with chemotherapy for PDAC and with chemotherapy plus anti-PD-1 for NSCLC in Q4 2025; Plan to report an interim safety and efficacy update on the Phase 1/2a trial of VS-7375 in 1H 2026; Expect to select the RP2D and plan to initiate monotherapy expansion cohorts in advanced PDAC, NSCLC, and other KRAS G12D-mutated solid tumors in 1H 2026; Expect to select the RP2D and plan to initiate combination expansion cohorts in CRC, PDAC, and NSCLC in 1H 2026; Plan to engage with the FDA to discuss our development path forward​, including potential registration-directed clinical trials in PDAC and NSCLC in 1H 2026."

New P1/2 trial • P1/2 data • Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

A Phase 1/2a Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors (clinicaltrials.gov) - P1/2 | N=330 | Recruiting | Sponsor: Verastem, Inc. | N=130 ➔ 330

Enrollment change • Monotherapy • Colorectal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

VS-7375: An oral, selective KRAS G12D dual ON/OFF inhibitor with superior anti-tumor efficacy relative to ON-only KRAS inhibitors (AACR-NCI-EORTC 2025) - P1/2 | "In 3D proliferation assays among a panel of human tumor cell lines, VS-7375 showed improved KRAS G12D potency and selectivity relative to the G12Di RMC-9805 and MRTX1133...To assess potential benefits of dual ON/OFF inhibition in KRAS G12D in vivo models, we compared efficacy relative to the ON-only inhibitors RMC-9805 (G12Di) and RMC-6236 (pan-RAS inhibitor)...Combination of VS-7375 with the anti-EGFR antibody cetuximab induced complete responses in all mice in a colorectal cancer xenograft model, and cetuximab also augmented the antitumor efficacy of VS-7375 in pancreatic and lung cancer models...VS-7375 is now being evaluated as monotherapy and in combinations in the US (NCT07020221). Altogether, these results demonstrate that the dual ON/OFF profile of VS-7375 corresponds with strong preclinical anti-tumor efficacy in KRAS G12D mutant cell lines and animal models, along with promising initial response rates for patients with KRAS G12D mutant solid tumors."

Clinical • Colorectal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Characterization of PSTA-5204, an oral KRAS G12D (ON) inhibitor with potent in vitro and in vivo efficacy (AACR-NCI-EORTC 2025) - "At ASCO, KRAS G12D (ON) inhibitor RMC-9805 and (ON/OFF) inhibitor VS-7375 showed promising clinical antitumor activity in NSCLC and PDAC. Notably, tumors in the PSTA-5204 15 mg/kg group showed near-complete regression by day 21 post-treatment. PSTA-5024 was well tolerated throughout the study and showed no evidence of hERG inhibition, supporting its safety profile.Conclusions PSTA-5204, an oral KRAS G12D (ON) inhibitor, demonstrates enhanced in vitro potency, near-complete tumor growth inhibition at a low dose of 7.5 mg/kg, along with a favorable pharmacokinetic and safety profile—highlighting its potential as a preclinical candidate."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Verastem Oncology Announces Encouraging Preliminary Data from Ongoing Phase 1/2a Dose Escalation Trial of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in Patients with KRAS G12D Mutant Solid Tumors (Businesswire) - "First two monotherapy dose levels (400 mg QD and 600 mg QD) cleared, with no dose-limiting toxicities reported. Promising anti-tumor activity observed in patients with various solid tumors, including advanced pancreatic ductal adenocarcinoma....Enrollment initiated for VS-7375 in combination with cetuximab in patients with advanced KRAS G12D mutant solid tumors, including colorectal cancer. Plan to report an interim safety and efficacy update on the Phase 1/2a trial in the first half of 2026."

Enrollment status • P1/2 data • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

First Patient Dosed in a Phase Ib/II Study of GFH375, an Oral KRAS G12D (ON/OFF) Inhibitor, Combined with Cetuximab or Chemotherapy for Advanced Solid Tumors including First-line Pancreatic Ductal Adenocarcinoma (PDAC) (HKEXnews) - "Phase Ib trial will be conducted at approximately 15 investigational sites including Peking University Cancer Hospital."

Trial status • Pancreatic Ductal Adenocarcinoma

Verastem Oncology Announces Updated Data from Partner GenFleet Therapeutics’ Phase 1/2 Monotherapy Study in China of GFH375 (VS-7375) in Advanced KRAS G12D Mutant Pancreatic Ductal Adenocarcinoma (Businesswire) - "As of the data cutoff of September 27, 2025, 59 efficacy-evaluable patients had at least one post-treatment tumor assessment and achieved an ORR of 40.7% (24/59) (confirmed and unconfirmed) and a disease control rate (DCR) of 96.7% (57/59) with the majority of patients (91.5%) experiencing a reduction in target lesions. Overall survival (OS) observed at month four was 92.2%. The median OS was not reached as of the data cutoff, with a median follow-up time of 5.65 months."

P1/2 data • Pancreatic Ductal Adenocarcinoma

Efficacy and Safety of GFH375 in Advanced Non-small Cell Lung Cancer Patients with KRAS G12D Mutation (IASLC-WCLC 2025) - P1/2 | "GFH375 is well tolerated. As monotherapy, it demonstrates promising anti-tumor activity in NSCLC pts with KRAS G12D mutations, warranting further clinical development."

Clinical • IO biomarker • Metastases • Anemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Solid Tumor • KEAP1 • KRAS • PIK3CA • STK11 • TP53

Verastem Oncology Announces Late-Breaking Abstract from Partner GenFleet Therapeutics’ Study in China of GFH375 (VS-7375) in Advanced Non-Small Cell Lung Cancer at IASLC 2025 World Conference on Lung Cancer (Businesswire) - "The study population includes 142 patients....GFH375 demonstrated an overall response rate (ORR) of 68.8% in non-small cell lung cancer (NSCLC) at the recommended Phase 2 dose of 600 mg QD. GFH375 demonstrated an ORR of 57.7% in efficacy evaluable patients with NSCLC across all dose levels. Mini oral presentation on Sunday, September 7, 2025..."

Late-breaking abstract • P1/2 data • Non Small Cell Lung Cancer