8-K: Verastem Oncology Announces Positive Updated Data from GenFleet Therapeutics Phase 1 Study of GFH375 (VS-7375) in China

Verastem Oncology announces positive updated data from its partner GenFleet Therapeutics' Phase 1 study in China of GFH375 (VS-7375), an oral KRAS G12D inhibitor, showing promising overall response rates in patients with pancreatic and lung cancers.

Summary

• Verastem Oncology's partner, GenFleet Therapeutics, presented updated data from a Phase 1 study of GFH375 (VS-7375) at the ASCO 2025 Annual Meeting.
• The study enrolled 62 patients in China with advanced KRAS G12D mutant solid tumors.
• As of May 16, 2025, data cutoff, 23 efficacy-evaluable patients with pancreatic ductal adenocarcinoma (PDAC) who received 400 or 600 mg daily achieved an overall response rate (ORR) of 52% and a disease control rate (DCR) of 100%.
• 12 efficacy-evaluable patients with non-small cell lung cancer (NSCLC) who received 400 or 600 mg daily achieved an ORR of 42% and a DCR of 83%.
• As of March 31, 2025, there were no dose-limiting toxicities (DLTs) observed across all dose levels (100-900 mg QD).
• Treatment-related adverse events (TRAEs) were mostly Grade 1/2, with the most common being diarrhea, nausea, vomiting, and anemia.
• Verastem plans to initiate a Phase 1/2a study in the U.S. to evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors, starting with a 400 mg dose.
• Verastem will host an investor webcast on June 2, 2025, to review the updated data.

Sentiment

Score: 8

Explanation: The announcement highlights positive clinical data, indicating potential for a new cancer therapy. The absence of significant safety concerns and the advancement to US trials further contribute to a positive outlook.

Positives

• GFH375 (VS-7375) demonstrated a 52% overall response rate (ORR) in patients with pancreatic ductal adenocarcinoma (PDAC).
• GFH375 (VS-7375) demonstrated a 42% ORR in patients with non-small cell lung cancer (NSCLC).
• The disease control rate (DCR) was 100% in PDAC patients and 83% in NSCLC patients.
• No dose-limiting toxicities (DLTs) were observed across all dose levels (100-900 mg QD).
• Treatment-related adverse events (TRAEs) were mostly Grade 1/2.
• Verastem is initiating a Phase 1/2a study in the U.S. to further evaluate VS-7375.

Negatives

• The study population in China had a high percentage of patients with metastatic disease (98%) and those who had received multiple prior lines of therapy (75%).
• Treatment-related adverse events (TRAEs) included diarrhea, nausea, vomiting, and anemia, although mostly Grade 1/2.

Risks

• The uncertainties inherent in research and development, such as the possibility of negative or unexpected results of clinical trials.
• Verastem may not see a return on investment on the payments made pursuant to the collaboration and option agreement with GenFleet, or that GenFleet may fail to fully perform under the agreement.
• The development and commercialization of product candidates may take longer or cost more than planned.
• Data may not be available when expected; preliminary and interim data may not be representative of more mature data.
• Product candidates may not receive regulatory approval, become commercially successful products, or result in new treatment options being offered to patients.

Future Outlook

Verastem plans to initiate a Phase 1/2a study in the U.S. to evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The company will assess the efficacy and safety of VS-7375, both as monotherapy and in combination, in patients with advanced solid tumors, such as pancreatic, colorectal, and non-small cell lung cancers.

Management Comments

• Dan Paterson, president and chief executive officer of Verastem Oncology, stated, We are encouraged by the initial efficacy and safety results from the Phase 1 portion of the study of GFH375 in China by our partner, GenFleet Therapeutics. The results presented at ASCO further support our advancement of our clinical program for VS-7375 in the U.S., as we believe there remains a significant opportunity to further improve on the efficacy seen to date with other KRAS G12D-selective agents. VS-7375s dual inhibition of both the ON/OFF states has the potential to drive deep and durable cancer responses and allow for better combinability with other agents.

Industry Context

This announcement is relevant to the oncology and biopharmaceutical industries, particularly concerning the development of targeted therapies for RAS/MAPK pathway-driven cancers. The KRAS G12D mutation is a significant target in cancer research, and the development of selective inhibitors like VS-7375 represents a potentially valuable advancement.

Comparison to Industry Standards

• The reported ORR of 52% in PDAC patients and 42% in NSCLC patients are promising compared to historical outcomes with standard chemotherapy regimens.
• Mirati Therapeutics' adagrasib (Krazati) has shown efficacy in KRAS G12C-mutated NSCLC, but VS-7375 targets the G12D mutation, addressing a different patient population.
• Amgen's sotorasib (Lumakras) is another KRAS G12C inhibitor, demonstrating the growing interest and competition in this therapeutic area.
• The dual ON/OFF inhibition mechanism of VS-7375 is designed to potentially drive deeper and more durable responses compared to other KRAS inhibitors.

Related Party Transactions

• The document discusses a collaboration between Verastem Oncology and GenFleet Therapeutics, involving the development of oncology programs related to RAS/MAPK pathway-driven cancers. Verastem has an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase 1 trial. Verastem exercised its option for VS-7375.

Stakeholder Impact

• Shareholders: Positive clinical data may increase investor confidence.
• Patients: Potential for a new treatment option for KRAS G12D mutant solid tumors.
• Employees: Advancement of clinical program may boost morale and job security.
• Partners: Strengthens the collaboration between Verastem and GenFleet.

Next Steps

• Verastem will host an investor webcast on June 2, 2025, to review the updated data.
• Verastem plans to initiate a Phase 1/2a study in the U.S. to evaluate the safety and efficacy of VS-7375.
• Verastem will assess the efficacy and safety of VS-7375, both as monotherapy and in combination, in patients with advanced solid tumors.

Key Dates

Recommendation

Keywords

VS-7375, GFH375, KRAS G12D inhibitor, Verastem Oncology, GenFleet Therapeutics, pancreatic ductal adenocarcinoma, non-small cell lung cancer, clinical trial, ASCO 2025, oncology