Verastem (NASDAQ:VSTM) executives outlined the company’s commercial and clinical priorities at an H.C. Wainwright event, highlighting the launch of its AVMAPKI FAKZYNJA CO-PACK for KRAS-mutated low-grade serous ovarian cancer and the advancement of its KRAS G12D inhibitor, VS-7375, across pancreatic, lung and colorectal cancers.
Nate Sanburn, Verastem’s chief business officer, said the company is pursuing two platforms: the commercial-stage combination of avutametnib and defactinib, marketed as the AVMAPKI FAKZYNJA CO-PACK, and VS-7375, its development-stage KRAS G12D program. The CO-PACK has received accelerated approval for KRAS-mutated low-grade serous ovarian cancer, while VS-7375 is being evaluated in Phase II studies in pancreatic cancer, non-small cell lung cancer and colorectal cancer.
Commercial launch and ovarian cancer program
Sanburn said the company made changes in the first quarter involving personnel and commercial tactics that contributed to its second-quarter performance. He noted that the launch experienced seasonality in the first quarter, which he said is expected in the disease setting, and that Verastem intends to continue refining its commercial approach through the end of 2026.
The company’s prescribing base has been split roughly 60% academic centers and 40% community practices, Sanburn said. Verastem is seeking to further expand engagement with community-based gynecologic oncologists and medical oncologists, with an emphasis on both new patient starts and keeping patients on treatment.
Jon Pachter, Verastem’s chief scientific officer, said patients with KRAS-mutated low-grade serous ovarian cancer in the Phase II RAMP 201 trial remained on therapy for an average of 18 months. He said that, as is common in a new oncology launch, some initial patients were relatively sicker, and the company is working to reach patients earlier in their treatment journey, including around first recurrence.
Verastem’s confirmatory Phase III RAMP 301 study is fully enrolled and is expected to read out next year, Sanburn said. The trial is designed to confirm results in the KRAS-mutated population and may provide an opportunity to expand into KRAS wild-type disease. Sanburn said the company estimates that approximately 30% of the low-grade serous ovarian cancer market is KRAS-mutated and 70% is KRAS wild type.
The company also expects to present analyses from RAMP 201 and an external-control comparison involving the GOG-0281 study at the upcoming International Gynecologic Cancer Society Congress.
Pancreatic cancer combination data
Pachter also discussed RAMP 205, which evaluated avutametnib and defactinib in combination with gemcitabine and Abraxane in frontline metastatic pancreatic cancer. He said the 29-patient study showed a 52% response rate and approximately one year of overall survival.
He said investigators are interested in evaluating the combination after pancreatic cancer progression on a RAS inhibitor. According to Pachter, resistance mechanisms can continue to feed into the MAP kinase pathway, including RAS amplification, RAF mutations and upstream receptor tyrosine kinases.
VS-7375 development strategy
Pachter described VS-7375 as a selective inhibitor designed to target both the active, or “on,” and inactive, or “off,” states of KRAS G12D. He said the company believes its compound has potent activity against both states, a long residence time and selectivity that could differentiate it from broader pan-RAS approaches.
Verastem expects to provide data on VS-7375 in October. Pachter said the company intends to report results with patient denominators of more than 20 in pancreatic and lung cancer cohorts, as well as colorectal cancer data for the combination with an anti-EGFR therapy.
- Pancreatic cancer: Pachter said approximately 40% of pancreatic cancers are driven by KRAS G12D mutations. The company believes second- and third-line pancreatic cancer could provide an opportunity to demonstrate the treatment’s potential.
- Colorectal cancer: Verastem is studying VS-7375 with cetuximab. Pachter said the company views anti-EGFR combinations as important in colorectal cancer, where he said single-agent RAS inhibitors have generally generated response rates near 10%.
- Lung cancer: The company has enrolled a 25-patient cohort of patients with asymptomatic brain metastases from lung cancer to assess whether VS-7375 can show activity in that setting.
Pachter said preclinical work supports combining KRAS inhibition with EGFR inhibition in pancreatic cancer. He cited research from Channing Der’s laboratory that identified EGFR inhibition as a potential way to enhance RAS inhibitor activity in pancreatic cancer models. Verastem has also generated preclinical data for VS-7375 plus cetuximab, he said.
Verastem selected 900 mg as its go-forward dose for VS-7375, while also evaluating 1,200 mg. Pachter said the higher dose has shown greater exposure and has been well tolerated, potentially providing flexibility for drug-drug interactions and dose optimization.
Beyond the ongoing Phase II studies, Verastem expects to establish three frontline Phase III programs for VS-7375 in the first half of next year. Pachter said future development in the broader RAS field will likely require combination approaches intended to extend duration of benefit and survival, including combinations involving the company’s FAK inhibitor and potential PRMT5 approaches.
About Verastem (NASDAQ:VSTM)
Verastem Oncology is a biopharmaceutical company focused on developing and commercializing targeted therapies for cancers driven by abnormalities in the RAS/MAPK signaling pathway. The company’s research is aimed at addressing cancers with limited treatment options, including ovarian cancer and other solid tumors.
Verastem’s principal products include avutometinib, a RAF/MEK pathway inhibitor, and defactinib, a focal adhesion kinase (FAK) inhibitor. The company has studied these therapies both individually and in combination, with the goal of improving cancer-cell response and overcoming treatment resistance.
