Biomea Fusion, Inc., is no longer pursuing oncology indications for BMF-219. No safety concerns or efficacy observations led to this study closure.

A Phase 1/1b dose finding study to determine the OBD(s) and RP2D(s) of BMF-219, a covalent menin inhibitor small molecule, in subjects with KRAS mutated unresectable, locally advanced, or metastatic NSCLC (Cohort 1), PDAC (Cohort 2), and CRC (Cohort 3).

This is a dose finding study to determine the safety and tolerability, pharmacokinetics and pharmacodynamics, and clinical activity of escalating doses of BMF-219 administered orally (PO) either once daily (QD) or twice daily (BID) in 28-day cycles. After observing acceptable safety performance in these dosing regimens, additional subjects will be enrolled to assess efficacy in the determination of the OBD for use as a RP2D.

Inclusion Criteria

1. Adults with a confirmed diagnosis of unresectable, locally advanced and/or metastatic Stage IIIB/IV NSCLC, Stage III/IV PDAC and/or Stage III/IV CRC with no curative-intent treatment options and documented activating KRAS mutation (without known additional actionable driver mutations such as EGFR, ALK or ROS1)

2. Documented progression and measurable disease after ≥ 1 prior line of systemic therapy (≥ 2 and

   ≤ 4 prior lines for NSCLC) with adequate washout period and resolution of treatment-related toxicities to ≤ Grade 2

3. ECOG PS of 0-2 (0-1 for PDAC) and a life expectancy > 3 months in the opinion of the Investigator

4. Adequate hematological, liver, and renal function

5. Men and women of childbearing potential must use adequate birth control measures for the duration of the trial and at least 90 days after discontinuing study treatment

Exclusion Criteria

1. Symptomatic and/or untreated CNS or brain metastasis, pre-existing ILD or pericardial/pleural effusion of ≥ grade 2 or requiring chronic oxygen therapy for COPD or pleural effusions
2. Serious concomitant disorder including infection
3. Known positive test for HIV, HCV, HBV surface antigen
4. Concurrent malignancy in the previous 2 years
5. Prior menin inhibitor therapy
6. Requiring treatment with a strong or moderate CYP3A inhibitor/inducer
7. Significant cardiovascular disease or QTcF or QTcB prolongation.
8. Major surgery within 4 weeks prior to first dose
9. Women who are pregnant or lactating.