Treatment With Novel KRAS Inhibitor Commences in Phase 1/1B Study, COVALENT-10

The COVALENT-102 study has started BMF-219 treatment in patients with KRAS-mutated, advanced solid tumors.

The first patient with a KRAS-mutated, unresectable, locally advanced, or metastatic advanced solid tumor has been dosed with BMF-219, signaling treatment initiation in the phase 1/1b COVALENT-102 study (NCT05631574).1

BMF-219 is a pan-KRAS inhibitor that targets KRAS G12C, G12D, G12R, and other KRAS locations. The agent is also the first Menin inhibitor to be investigated for the treatment of KRAS-mutated non–small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC).

“We are eager to explore the potential of BMF-219 as a pan-KRAS inhibitor in patients with three of the most prominent KRAS-mutant solid tumor types, including those with tumors that have failed to respond to investigational and approved mutation-specific KRAS inhibitors,” said Steve Morris, MD, chief medical officer of Biomea Fusion, Inc, in a press release. “As a covalent Menin inhibitor, we believe BMF-219 has critical advantages over late stage, mutation-specific inhibitors of KRAS including independence on the KRAS activation state, reduced likelihood for acquisition of resistance mutations, and its potential to address multiple activating KRAS mutations.”

In the open-label, multi-cohort, multicenter study, a dose-escalation, and dose-expansion will occur to assess the safety, tolerability, and optimal dose of BMF-219 in patients with KRAS-mutated NSCLC, CRC, and PDAC. The agent will be administered orally, once daily or twice per day during the dose-escalation phase. The coprimary end points of the study are the number of patients who experience dose-limiting toxicities and the objective response rate. The secondary end points include the number of patients with treatment-emergent adverse events, pharmacokinetics, duration of response, and disease control rate.2

To be eligible for inclusion, patients must have a confirmed diagnosis of unresectable, locally advanced, and/or metastatic stage IIIB/IV NSCLC, stage III/IV PDAC, and/or stage III/IV CRC for which there are not curative therapies, and a documented KRAS mutation. Patients are also required to show documented progression and measurable disease following at least 1 prior line of systemic therapy, with a maximum of 4 prior treatment lines. Additionally, an ECOG performance score of 0-2, and adequate hematologic, liver, and renal function are required.

Any person with symptomatic and/or untreated central nervous system (CNS) metastasis or other pre-existing CNS involvement will be excluded from the study. The study also excludes those with serious concomitant disorder, concurrent malignancy in the previous 2 years, and significant cardiovascular disease. Patients who were previously treated with a Menin inhibitor, require a CYP3Z inhibitor or inducer, or had major surgery within 4 weeks of the start of the study are also ineligible.

Patients with KRAS-mutated NSCLC, CRC, and PDAC who meet the inclusion criteria are currently being recruited as study sites in Arizona, Illinois, and Virginia. Other areas in the United States that have not begun recruitment include California, Missouri, New York, Ohio, Texas, and Washington.

According to Biomea Fusion, Inc, BMF-219 showed high sensitivity in patients with KRAS-mutated solid tumors in preclinical studies. The agent also displayed a profile that was different than FDA-approved KRAS inhibitors like sotorasib (Lumakras) and adagrasib (Krazati).1

REFERENCES:

1. Biomea Fusion doses first patient in phase 1/1b clinical trial (COVALENT-102) of BMF-219 in KRAS mutant solid tumors. Biomea Fusion, Inc. News release. January 17, 2023. Accessed January 18, 2023. https://bit.ly/3QQIk99

2. Study of covalent menin inhibitor BMF-219 in adult patients with KRAS driven non-small cell lung cancer, pancreatic cancer, and colorectal cancer. ClinicalTrials.gov. Updated December 27, 2022. Accessed January 18, 2023. https://clinicaltrials.gov/ct2/show/NCT05631574?term=COVALENT-102&draw=2&rank=1