Verastem Oncology Reports Positive Initial Results from RAMP 205 Trial in First-Line Metastatic Pancreatic Cancer

Verastem Oncology has announced promising interim safety and efficacy results from its ongoing RAMP 205 Phase 1/2 clinical trial, which evaluates the combination of avutometinib and defactinib with gemcitabine and Nab-paclitaxel for first-line treatment in patients with metastatic pancreatic cancer. As of May 14, 2024, in the study's most mature dose cohort, 83% of patients achieved a confirmed partial response. The initial results will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 1, 2024.

The trial involves different dose and schedule cohorts to determine the optimal Phase 2 dose. Specifically, patients in dose level 1 received 2.4 mg of avutometinib twice weekly, 200 mg of defactinib twice daily for 3 weeks out of every 4, along with 800 mg/m² of gemcitabine and 125 mg/m² of Nab-paclitaxel on days 1, 8, and 15 of each cycle. This cohort showed an 83% partial response rate, though one patient experienced dose-limiting toxicity (DLT) in the form of febrile neutropenia. Additional patients were subsequently enrolled, and the dose level was cleared for further study.

The study continues to evaluate other dose regimens to solidify the recommended Phase 2 dose. Dr. John Hayslip, Chief Medical Officer of Verastem Oncology, emphasized the significance of targeting the RAS/MAPK pathway, given that over 90% of pancreatic tumors exhibit a KRAS mutation. He noted that the data supports the intent behind the PanCAN Therapeutic Accelerator Award to expedite the development of new therapies.

Dr. Anna Berkenblit, Chief Scientific and Medical Officer at PanCAN, highlighted the critical need for new treatment options for pancreatic cancer, expressing hope that the results from this study could lead to improved patient outcomes.

As of the May 14 data cutoff, 41 patients had been treated across four cohorts. The responses varied, with dose level 1 showing significant promise. Patients in the trial had a median age of 64 years, with 46% male and 49% having an ECOG performance status of one. Of the 26 patients who had the opportunity for their first scan, 21 experienced a reduction in target lesion size.

Initial interim safety data indicated that 12 patients experienced 19 treatment-emergent serious adverse events (SAEs), with 11 patients experiencing grade ≥3 SAEs. These included increased blood bilirubin, biliary obstruction, febrile neutropenia, pulmonary embolism, sepsis, anemia, pneumoperitoneum, septic shock, skin infection, malignant neoplasm progression, and vomiting. Two patients discontinued treatment due to adverse events.

Verastem will discuss these interim results during an investor conference call and webcast on May 24, 2024. The company aims to advance its pipeline focused on RAS/MAPK-driven cancers, developing novel small-molecule drugs that inhibit critical cancer signaling pathways.

Pancreatic cancer, a leading cause of cancer-related deaths, is predominantly treated with surgery, chemotherapy, and radiation. However, the five-year survival rate for metastatic pancreatic cancer remains at a dismal 3%. The RAMP 205 study aims to bring new hope by evaluating avutometinib and defactinib in combination with standard chemotherapy.

Verastem's investigational combination of avutometinib and defactinib has shown promise by inhibiting the RAS/MAPK pathway more effectively than existing therapies. The FDA has granted Breakthrough Therapy Designation for this combination in treating recurrent low-grade serous ovarian cancer, in addition to Orphan Drug Designation.

Currently, Verastem is involved in multiple clinical trials, including RAMP 301, an international Phase 3 trial for recurrent low-grade serous ovarian cancer, and RAMP 201, a Phase 2 trial for the same condition. The company also collaborates with Amgen and Mirati to evaluate avutometinib in combination with other treatments for KRAS-mutant cancers.

Verastem Oncology remains committed to developing new therapies that improve the lives of cancer patients, with a strong focus on RAS/MAPK-driven cancers.