Treatment with Novel KRAS Inhibitor Begins in Phase 1/1B Study, COVALENT-10

The COVALENT-102 study initiated treatment with BMF-219 in patients with advanced solid tumors with the KRAS mutation.

The first patient with a kras– mutated, unresectable, locally advanced or metastatic advanced solid tumor was administered with BMF-219, signaling the initiation of treatment in the Phase 1/1b study COVALENT-102 (NCT05631574).1

BMF-219 is a pan-KRAS inhibitor that targets kras G12C, G12D, G12R and others kras locations. The agent is also the first menin inhibitor to be studied for the treatment of krasmutated 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 important KRAS-mutant solid tumor types, including those with tumors that have failed to respond to investigational mutation-specific, approved KRAS inhibitors,” he said. said Steve Morris, MD, chief medical officer of Biomea Fusion, Inc, in a press release. “As a covalent inhibitor of menin, we believe BMF-219 has key advantages over specific late stage mutation inhibitors of KRAS, including independence from kras activation status, reduced likelihood of acquiring resistance mutations, and its potential to address multiple activation kras mutations”.

In the open-label, multicohort, multicenter study, dose escalation and dose expansion will occur to evaluate the safety, tolerability, and optimal dose of BMF-219 in patients with kras-mutated NSCLC, CRC and PDAC. The agent will be administered orally, either once daily or twice daily during the dose escalation phase. The co-primary endpoints of the study are the number of patients experiencing dose-limiting toxicities and objective response rate. Secondary endpoints include 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 PDACand/or stage III/IV CRC for which there is no documented curative therapy kras mutation. Patients must also have documented progression and measurable disease after at least 1 prior line of systemic therapy, with up to 4 prior lines of treatment. Additionally, an ECOG performance score of 0-2 and adequate haematologic, hepatic, and renal function are required.

Any person with symptomatic and/or untreated central nervous system (CNS) metastases or other pre-existing CNS involvement will be excluded from the study. The study also excluded those with serious comorbidities, comorbidities within the previous 2 years, and significant cardiovascular disease. Patients who have been previously treated with a menin inhibitor, require a CYP3Z inhibitor or inducer, or had major surgery within 4 weeks of study initiation are also ineligible.

Patients with krasNSCLC, CRC, and mutant PDACs meeting the inclusion criteria are currently recruited as study sites in Arizona, Illinois, and Virginia. Other areas in the US that have not begun recruiting include California, Missouri, New York, Ohio, Texas and Washington.

According to Biomea Fusion, Inc, BMF-219 has shown high sensitivity in patients with kras-solid tumors mutated in preclinical studies. The agent also showed a different profile from FDA-approved KRAS inhibitors such as sotorasib (Lumakras) and adagrasib (Krazati).1


1. Biomea Fusion doses first patient in Phase 1/1b clinical study (COVALENT-102) of BMF-219 in KRAS mutant solid tumors. Biomea Fusion, Inc. Press Release. January 17, 2023. Accessed January 18, 2023.

2. Study of the covalent menin inhibitor BMF-219 in adult patients with KRAS-driven non-small cell lung cancer, pancreatic cancer, and colorectal cancer. Updated December 27, 2022. Accessed January 18, 2023.

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