Study of Covalent Menin Inhibitor BMF-219 in Adult Patients With KRAS Driven Non-Small Cell Lung Cancer, Pancreatic Cancer, and Colorectal Cancer

Brief summary public domain (ClinicalTrials.gov)

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).

Detailed description public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Drug: BMF-219. BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.

Arm public domain (ClinicalTrials.gov)

Escalation Phase (experimental): Dose Escalation Phase will group all disease indications (NSCLC, PDAC, and CRC) together to assess the safety of each dose level. Participants will receive escalating dose BMF-219 orally once per day or twice per day to identify the OBD/RP2D (Optimal Biologic Dose/Recommended Ph2 Dose).

Arm public domain (ClinicalTrials.gov)

Expansion Phase (experimental): Dose Expansion Phase will enroll additional subjects independently in each disease indication: Cohort 1: Participants with NSCLC Cohort 2: Participants with PDAC Cohort 3: Patients with CRC Cohorts 1, 2, and 3 will receive BMF-219 at the OBD/ RP2D to further assess the safety and efficacy of the investigational drug.

Primary outcome public domain (ClinicalTrials.gov)

To determine the OBDs/RP2Ds of BMF-219 monotherapy in subjects with KRAS-driven unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.. OBD/RP2D as determined by the number of subjects receiving BMF-219 monotherapy who experience Dose-Limiting Toxicities (DLTs) within each dose level. A DLT is defined as any clinically significant Adverse Event within 28 days of starting BMF-219 treatment and considered to be related to the IMP. Adverse Events will be assessed per CTCAE v5.0. Time frame: 30 months.

Primary outcome public domain (ClinicalTrials.gov)

To determine the OBDs/RP2Ds of BMF-219 monotherapy in subjects with KRAS-driven unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.. OBD/RP2D as measured by objective response rate (ORR). ORR will be assessed using RECIST 1.1 per investigator assessment. Time frame: 30 months.

Secondary outcome public domain (ClinicalTrials.gov)

To evaluate the safety and tolerability of BMF-219 monotherapy.. Time frame: 46 months.

Secondary outcome public domain (ClinicalTrials.gov)

To evaluate the pharmacokinetics of BMF-219.. Time frame: 46 months.

Secondary outcome public domain (ClinicalTrials.gov)

To evaluate the pharmacokinetics of BMF-219.. Time frame: 46 months.

Secondary outcome public domain (ClinicalTrials.gov)

To evaluate the pharmacokinetics of BMF-219.. Time frame: 46 months.

Secondary outcome public domain (ClinicalTrials.gov)

To evaluate the efficacy of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.. Time frame: 46 months.

Secondary outcome public domain (ClinicalTrials.gov)

To evaluate the efficacy of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.. Time frame: 46 months.

Eligibility public domain (ClinicalTrials.gov)

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.

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 13 participants (actual).

Why stopped public domain (ClinicalTrials.gov)

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