VS-7375 / Verastem, GenFleet Therap - LARVOL DELTA

Efficacy and Safety of GFH375 in Advanced KRASG12D Mutant Non-Small Cell Lung Cancer (NSCLC) Patients (IASLC-WCLC 2026) - P1/2 | "Updated data from approximately 75 patients with a minimum follow-up of more than 4 months will be presented at the conference, along with genetic co-alteration analyses derived from NGS profiling of baseline tumor tissue and paired baseline/end-of-treatment ctDNA samples. Conclusions : GFH375 exhibits compelling clinical efficay in patients with KRAS G12D mutant NSCLC, accompanied by a tolerable safety profile, warranting further clinical development."

Clinical • IO biomarker • Metastases • Dyslipidemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Renal Disease • Sarcoma • Solid Tumor • BCL2L11 • CDKN2A • KEAP1 • KRAS • STK11 • TP53

Oral KRAS G12D inhibitor GFH375 for previously treated advanced solid tumors with KRASG12D mutations: a phase 1 trial. (PubMed, Nat Med) - P1/2 | "The phase 2 portion of this trial with expansion cohorts for NSCLC, PDAC, CRC and other solid tumors is ongoing. ClinicalTrials.gov identifier: NCT06500676 ."

IO biomarker • Journal • P1 data • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Septic Shock • Solid Tumor • KRAS

GenFleet Therapeutics disclosed that its clinical program evaluating GFH375 combined with cetuximab has been placed on the proposed Breakthrough Therapy Designation list by China’s Center for Drug Evaluation (TipRanks) - "The regimen targets metastatic colorectal cancer patients with KRAS G12D mutations whose disease has progressed after standard chemotherapies, and the public comment period on the designation runs until 24 September 2026."

Breakthrough therapy • Colorectal Cancer

Anti-tumor efficacy of the selective oral KRAS G12D dual ON/OFF inhibitor VS-7375 as a single agent and in combination with pan-RAS inhibition (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Clinical • Combination therapy • Oncology • KRAS

Verastem Oncology today announced it will host an investor event on Wednesday, October 14,at 8:00 am ET to present initial efficacy and updated safety and tolerability data for VS-7375 in pancreatic, lung, and colorectal cancers from the ongoing TARGET-D clinical development program (Businesswire) - "The upcoming presentation will build on the clinical update reported in June 2026 and provide the first broader safety and efficacy assessment of VS-7375 across these tumor types...The TARGET-D program includes the Phase 1/2 TARGET-D 101 (NCT07020221)...as well as three registration-directed Phase 2 trials currently enrolling patients: TARGET-D 201 (NCT07644559) for metastatic PDAC, TARGET-D 202 (NCT07659782) for advanced NSCLC, and TARGET-D 203 (NCT07659795) for metastatic CRC."

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

Preliminary efficacy of GFH375 in patients with advanced cholangiocarcinoma or colorectal cancer harboring KRAS G12D mutation. (ASCO 2026) - P1/2 | "GFH375 monotherapy has demonstrated promising antitumor activities in heavily treated pts with CCA and CRC. GFH375 monotherapy in CCA and in combination with other anti-tumor therapies for CRC is under development."

Clinical • Metastases • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • BCL2L11 • KRAS • PIK3CA • RUNX1 • SMAD4 • TP53

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

Emerging Therapeutic Strategies for Non-G12C KRAS Mutations in Colorectal Cancer: Focusing on G12D and G12V. (PubMed, J Gastrointest Cancer) - "The non-G12C KRAS era is beginning, but durable benefit in CRC will likely require rational combinations tailored to allele, lineage, and resistance biology."

Journal • Review • Colorectal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • KRAS

A Phase II Study of GFH375 Combined With GFS202A or GFH276 Versus GFH375 Monotherapy in Patients With Previously Treated Locally Advanced Unresectable or Metastatic Pancreatic Cancer Harboring KRAS G12D Mutation (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc.

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

GenFleet Therapeutics (Shanghai)…is pleased to announce GFH375…has advanced into a multicenter, open-label, randomized controlled registrational phase III study (’Kylin-Flight 01’) in China evaluating monotherapy efficacy and safety versus docetaxel in patients with KRAS G12D-mutant locally advanced, unresectable, or metastatic…NSCLC who have failed standard-of-care therapy (HKEXnews) - "The trial will be conducted across more than 40 clinical sites nationwide, with the first patient recently dosed at Nanjing Drum Tower Hospital."

Trial status • Non Small Cell Lung Cancer

GenFleet Therapeutics…is pleased to announce the initiation of a three-arm, parallel-controlled phase II study evaluating two novel combination regimens versus monotherapy of GFH375, an oral KRAS G12D (ON/OFF) inhibitor, among pretreated KRAS G12D-mutant patients with locally advanced unresectable or metastatic pancreatic cancer (HKEXnews) - "The multicenter, open-label, randomized controlled study will be conducted across tens of clinical sites in the Chinese mainland; with Ruijin Hospital Affiliated to Shanghai Jiao Tong University's School of Medicine as the leading site. The two combination therapies include GFH375 plus GFS202A, the world’s first cachexia-targeted bispecific antibody (GDF15/IL-6 bispecific antibody), and GFH375 plus GFH276, a Pan RAS (ON) inhibitor."

New P2 trial • Pancreatic Cancer

A Study to Evaluate GFH375 Versus Docetaxel in Participants With Non-Small Cell Lung Cancer With KRAS G12D Mutation (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | Not yet recruiting ➔ Recruiting

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

VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor in Advanced Solid Tumors:…Expected Key Milestones (Businesswire) - "(i) Report updated VS-7375 clinical data in October 2026; (ii) Complete enrollment across all three TARGET-D Phase 2 trials by the end of 2026; (iii) Meet with the FDA before the end of the year to review Phase 3 pivotal trial designs in 1L mPDAC, 1L mCRC, and 1L advanced NSCLC; (iv) Enroll the first patient in each of the Phase 3 pivotal trials in the first half of 2027."

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

At the end of June, the Company completed target enrollment in TARGET-D 101 PDAC and NSCLC monotherapy cohorts and CRC cetuximab combination cohorts (Businesswire) - "More than 200 patients have been treated with VS-7375 in the TARGET-D 101 dose escalation and expansion study. The Company has also cleared the 1200 mg daily (QD) dose of VS-7375 with no dose-limiting toxicities (DLTs) observed. Patients will continue to be evaluated at this dose in the TARGET-D 101 dose escalation study to support Project Optimus requirements..."

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

TARGET-D 202: A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=105 | Recruiting | Sponsor: Verastem, Inc. | Not yet recruiting ➔ Recruiting

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

Verastem Oncology…announced that the first patient has been dosed in the TARGET-D 203 Phase 2 registration-directed trial evaluating VS-7375, an investigational oral KRAS G12D (ON/OFF) inhibitor with best-in-class potential, to treat patients with KRAS G12D-mutated metastatic colorectal cancer (Businesswire) - "The Company has now initiated treatment across all three of its TARGET-D registration-directed Phase 2 clinical trials evaluating VS-7375 in patients with KRAS G12D-mutated pancreatic, colorectal, and lung cancers...Patient follow-up continues to mature across monotherapy and combination cohorts, and the Company expects to share an update in the second half of 2026."

Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

TARGET-D 203: A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Colorectal Cancer (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Verastem, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Verastem Oncology Doses First Patient in TARGET-D 202 Phase 2 Registration-Directed Trial of VS-7375 for KRAS G12D-Mutated Advanced Non-Small Cell Lung Cancer (Businesswire) - "TARGET-D 202 (NCT07659782) is a global, open-label, Phase 2 registration-directed trial evaluating VS-7375 monotherapy at the recommended Phase 2 dose (RP2D) of 900 mg daily (QD) in patients with unresectable locally advanced or metastatic KRAS G12D-mutated NSCLC whose disease has progressed following prior treatment with platinum-based chemotherapy and an anti-PD-(1) therapy....A cohort in the study will also evaluate VS-7375 in non-small cell lung cancer patients with asymptomatic untreated brain metastases."

Trial status • Non Small Cell Lung Cancer

A Study to Evaluate GFH375 Versus Docetaxel in Participants With Non-Small Cell Lung Cancer With KRAS G12D Mutation (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc.

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Expected Key Milestones (Businesswire) - "(i) Report an update on the TARGET-D 101 trial in 2H 2026; (ii) Complete target enrollment in TARGET-D 101 PDAC and NSCLC monotherapy cohorts and mCRC cetuximab combination cohorts by the end of June 2026; (iii) Announce first patient dosed in the TARGET-D 202 and TARGET-D 203 clinical trials in mid-2026; (iv) Complete enrollment across all three TARGET-D Phase 2 trials by the end of 2026; (v) Meet with the U.S. Food and Drug Administration (FDA) before the end of the year to review Phase 3 pivotal trial designs in 1L mPDAC, 1L mCRC and 1L advanced NSCLC; (vi) Enroll the first patient in each of the Phase 3 pivotal trials in the first half of 2027."

FDA event • New P3 trial • P1/2 data • Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

TARGET-D 202: A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=105 | Not yet recruiting | Sponsor: Verastem, Inc.

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

TARGET-D 203: A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Colorectal Cancer (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Verastem, Inc.

New P2 trial • Colorectal Adenocarcinoma • 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 | Recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

The KRAS G12D Inhibitor Pipeline Grows. (PubMed, Cancer Discov) - "At this year's ASCO Annual Meeting, investigators also presented encouraging early clinical data for several KRASG12D-selective inhibitors, including RNK08594, GFH375, and DN022150, suggesting that this type of drug could play a role in the treatment of several solid tumors, such as pancreatic ductal adenocarcinoma and non-small cell lung cancer."

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