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

NCT05631574 | Terminated Phase 1 FDA Drug

• 1 other identifier: COVALENT-102
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 23

Brief Summary

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).

Conditions

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

Keywords

Oral Covalent Menin Inhibitor; Relapsed; Refractory; Irreversible Menin Inhibitor; Menin Inhibitor; Unresectable; Locally Advanced; Metastatic; Menin; Menin Therapy; KRAS; KRAS Mutated

Outcome Measures

Primary Outcomes (2)

• 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.

  30 months

• 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.

  30 months

Secondary Outcomes (6)

• To evaluate the safety and tolerability of BMF-219 monotherapy.

  46 months

• To evaluate the pharmacokinetics of BMF-219.

  46 months

• To evaluate the pharmacokinetics of BMF-219.

  46 months

• To evaluate the pharmacokinetics of BMF-219.

  46 months

• To evaluate the efficacy of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.

  46 months

Study Arms (2)

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).

Drug: BMF-219

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.

Drug: BMF-219

Interventions

BMF-219 DRUG

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

Escalation Phase; Expansion Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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
• ECOG PS of 0-2 (0-1 for PDAC) and a life expectancy \> 3 months in the opinion of the Investigator
• Adequate hematological, liver, and renal function
• 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

You may not qualify if:

• 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
• Serious concomitant disorder including infection
• Known positive test for HIV, HCV, HBV surface antigen
• Concurrent malignancy in the previous 2 years
• Prior menin inhibitor therapy
• Requiring treatment with a strong or moderate CYP3A inhibitor/inducer
• Significant cardiovascular disease or QTcF or QTcB prolongation.
• Major surgery within 4 weeks prior to first dose
• Women who are pregnant or lactating.

Sponsors & Collaborators

• Biomea Fusion Inc.: lead

Study Sites (23)

Cancer Treatment Centers of America - Phoenix

Goodyear, Arizona, 85338, United States

Location

California Cancer Associates for Research and Excellence (cCARE)

Encinitas, California, 92024, United States

Location

University of California, San Diego

La Jolla, California, 92037, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80237, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Cancer Treatment Centers of America - Atlanta

Atlanta, Georgia, 30269, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern Univeristy

Chicago, Illinois, 60611, United States

Location

Cancer Treatment Centers of America - Chicago

Zion, Illinois, 60099, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System - PPDS

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Pancreatic Neoplasms; Colorectal Neoplasms; Recurrence; Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Study Officials

• Steve Morris, MD

  Biomea Fusion Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is an ascending multiple dose clinical trial followed by cohort expansion. The dose escalation part is primarily intended to identify the optimal biologic dose (OBD)(s) of BMF-219 and to obtain initial safety and tolerability information regarding the compound when administered orally to subjects with KRAS mutated unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC. This study will also evaluate the PK/PD profiles of multiple dose administration of BMF-219. Following completion of the dose escalation, cohort and arm-specific expansion cohorts will commence in order to further confirm the safety and tolerability of BMF-219 dosed at or near the OBD.

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: November 30, 2022
• Study Start: January 12, 2023
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: February 7, 2025

Record last verified: 2025-02

Locations

US (19); KR (4)