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

Biomea Fusion

Status and phase: Enrolling; Phase 1

Conditions: Stage III NSCLC; Stage III Non-small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Colorectal Cancer; Relapsed Cancer; PDAC; KRAS Mutation-Related Tumors; Stage IV Non-small Cell Lung Cancer; Refractory Cancer; Stage IV Pancreatic Cancer; Non Small Cell Lung Cancer; CRC; Stage IV NSCLC; Stage IV Colorectal Cancer; NSCLC; Colorectal Cancer; Pancreatic Cancer

Treatments: Drug: BMF-219

Study type: Interventional

Funder types: Industry

Identifiers

NCT05631574

COVALENT-102

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

Escalation Phase

Experimental group

Description:

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).

Treatment:

Drug: BMF-219

Expansion Phase

Experimental group

Description:

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.

Treatment:

Drug: BMF-219