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

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

VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in Advanced Solid Tumors (Businesswire) - "Key Milestones Expected for the Second Half of 2025: (i) Report a preliminary update on the Phase 1 monotherapy dose escalation in Q4 2025; (ii) Subject to the results of the Phase 1 monotherapy dose escalation, the Company plans to initiate monotherapy expansion cohorts in both advanced PDAC and NSCLC; (iii) Initiate the dose escalation cohorts in combination with cetuximab, chemotherapy, and chemotherapy with checkpoint-inhibitor for CRC, PDAC, and NSCLC, respectively, in Q4 2025; (iv) Subject to the results of the Phase 1 dose escalation combinations cohorts with VS-7375, the Company plans to initiate a combination expansion cohort in CRC, PDAC, and NSCLC."

P1 data • Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

FDA grants fast track designation to Verastem’s pancreatic cancer drug (Investing.com) - "The U.S. Food and Drug Administration has granted Fast Track Designation to Verastem Oncology’s...VS-7375, an oral KRAS G12D inhibitor, for the treatment of pancreatic cancer with KRAS G12D mutations, the company announced Thursday...The designation applies to VS-7375 for first-line treatment of locally advanced or metastatic pancreatic adenocarcinoma with KRAS G12D mutations, as well as for patients who have received at least one prior line of standard therapy...Enrollment is currently ongoing in a U.S. Phase 1/2a clinical trial evaluating VS-7375 in patients with advanced KRAS G12D mutant solid tumors, including pancreatic cancer. The company plans to expand the trial globally...Upon completion of the dose-escalation phase, Verastem plans to select a recommended Phase 2 dose and assess VS-7375 as monotherapy in expansion cohorts for advanced pancreatic cancer and non-small cell lung cancer."

Fast track • Trial status • Non Small Cell Lung Cancer • Pancreatic Adenocarcinoma • Solid Tumor

Verastem Oncology Announces First Patient Dosed with VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in a U.S. Phase 1/2a Trial in KRAS G12D Advanced Solid Tumors (Businesswire) - "Verastem Oncology...announced that the first patient has been dosed in VS-7375-101, the U.S. Phase 1/2a clinical trial evaluating VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, in patients with advanced KRAS G12D mutant solid tumors....VS-7375-101 is a Phase 1/2a study being conducted in the U.S., with plans to expand globally, and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The monotherapy dose escalation phase of the study will use a starting dose of 400 mg, based on an efficacious dose identified in the Phase 1/2 study conducted in China....Phase 1 dose-escalation study to evaluate VS-7375 in the U.S., with plans to expand as monotherapy into pancreatic cancer and non-small cell lung cancer cohorts, along with colorectal cancer in combination with cetuximab."

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

A Phase II Study to Evaluate GFH375 in Patients With KRAS G12D Mutant Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=83 | Not yet recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc.

Monotherapy • New P2 trial • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

A Phase 1/2a Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Recruiting | Sponsor: Verastem, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

A Phase 1/2a Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Not yet recruiting | Sponsor: Verastem, Inc.

Monotherapy • New P1/2 trial • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Verastem Oncology Announces Updated Data from Partner GenFleet Therapeutics’ Phase 1 Study in China of GFH375 (VS-7375), an Oral KRAS G12D (ON/OFF) Inhibitor (Businesswire) - P1/2 | N=390 | NCT06500676 | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | "GenFleet reported that 62 patients were enrolled in the Phase 1 portion of the study in China, receiving oral doses ranging from 100 to 900 mg daily. In the study, 98% of patients had metastatic disease, and 75% had received ≥2 prior lines of therapy. As of the data cutoff of May 16, 2025, 23 efficacy-evaluable patients with PDAC and 12 efficacy-evaluable patients with NSCLC, who received daily dosages of 400 or 600 mg and had at least one post-treatment tumor assessment, achieved an ORR of 52% and a disease control rate (DCR) of 100%, and an ORR of 42% and a DCR of 83%, respectively. As of the cutoff date of March 31, 2025, GenFleet reported that there were no dose-limiting toxicities (DLTs) observed across all dose levels (100-900 mg QD), and the treatment-related adverse events (TRAEs) were mostly Grade 1/2."

P1 data • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Verastem Oncology Announces Positive Updated Results from RAMP 205 Evaluating Avutometinib Plus Defactinib in Combination with Standard-of-Care Chemotherapy in Frontline Metastatic Pancreatic Ductal Adenocarcinoma (Businesswire) - P1b/2a | N=40 | RAMP205 (NCT05669482) | Sponsor: Verastem, Inc. |"As of April 25, 2025, 60 patients (12 per cohort) had been treated in one of five dose regimens with the combination of avutometinib and defactinib with gemcitabine and Nab-paclitaxel in frontline metastatic PDAC. In the dose level 1 cohort, 12 patients received 2.4 mg of avutometinib twice a week (BIW), 200 mg of defactinib twice a day (BID) for 3 weeks out of every 4 and 800 mg/m2 of gemcitabine and 125 mg/m2 of Nab-paclitaxel on a schedule of day 1, day 8 and day 15. In dose level 1, 83% (10/12) of patients achieved partial responses (8 confirmed and 2 unconfirmed who remain on treatment)....The Company is now developing plans for a registrational Phase 3 front-line metastatic PDAC trial to begin in 2026....Company will host an R&D investor webcast on Monday, June 2 at 11:00 am CDT to review the updated RAMP 205 data as well as updated data on VS-7375 presented at ASCO."

New P3 trial • P1/2 data • Pancreatic Ductal Adenocarcinoma