Treatment with the new KRAS inhibitor begins in the phase 1/1B study, COVALENT-10

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

The first patient with KRAS– mutated, inoperable, locally advanced or metastatic solid tumor was dosed with BMF-219, signaling the start of treatment in the phase 1/1b study COVALENT-102 (NCT05631574).1

BMF-219 is a pan-KRAS targeting inhibitor KRAS G12C, G12D, G12R and others KRAS locations. The agent is also the first menin inhibitor to be tested for treatment 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 the three most prominent types of KRAS-mutated solid tumors, including those with tumors that have not responded 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 KRAS inhibitors, including independence from KRAS activation state, reduced probability of acquiring resistance mutations, and its potential to address the problem of multiple activation KRAS mutations.”

In an open-label, multi-cohort, multi-center 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, once a day or twice a day during the dose increase phase. The co-primary endpoints of the study are the number of patients who experienced dose-limiting toxicity and the objective response rate. Secondary endpoints include the number of patients with treatment-emergent adverse events, pharmacokinetics, duration of response, and disease control rate.2

To meet the inclusion criteria, patients must have a confirmed diagnosis of inoperable, locally advanced and/or metastatic stage IIIB/IV NSCLC, stage III/IV PDACand/or CRC stage III/IV for which there are no curative therapies, and they are documented KRAS mutation. Patients must also demonstrate documented progression and measurable disease after at least 1 prior line of systemic therapy, with a maximum of 4 prior lines of treatment. In addition, an ECOG performance score of 0-2 and adequate hematologic, hepatic, and renal function are required.

Any person with symptomatic and/or untreated central nervous system (CNS) metastases or other existing CNS involvement will be excluded from the study. The study also excludes those with a serious comorbidity, concurrent malignancy in the previous 2 years, and significant cardiovascular disease. Patients previously treated with a menin inhibitor, requiring a CYP3Z inhibitor or inducer, or having major surgery within 4 weeks of the start of the trial were also ineligible.

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

According to Biomea Fusion, Inc, BMF-219 has shown high sensitivity in patients with KRAS-mutated solid tumors in preclinical studies. The agent also showed a profile that was different from that of FDA-approved KRAS inhibitors such as 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 Mutated Solid Tumors. Biomea Fusion, Inc. News Release January 17, 2023. Accessed January 18, 2023. https://bit.ly/3QQIk99

2. Study of the covalent menin inhibitor BMF-219 in adult patients with KRAS-induced 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

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