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

A Phase 1/1b Dose Finding Study of BMF-219, an Oral Covalent Menin Inhibitor, in Adult Patients With Unresectable, Locally Advanced, or Metastatic Non-small Cell Lung Cancer (NSCLC), Pancreatic Cancer (PDAC), and Colorectal Cancer (CRC)

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).

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Pancreatic Cancer; NSCLC; Non Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; CRC; KRAS Mutation-Related Tumors; Relapsed Cancer; Refractory Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Colorectal Cancer; Stage III Non-small Cell Lung Cancer; Stage III NSCLC; PDAC; Stage IV NSCLC; Stage III Colorectal Cancer
• Intervention / Treatment: Drug: BMF-219

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System - PPDS
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Cancer Treatment Centers of America - Phoenix
  • California
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research and Excellence (cCare)
    • La Jolla, California, United States, 92037
      • University of California, San Diego
  • Colorado
    • Denver, Colorado, United States, 80237
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30269
      • Cancer Treatment Centers of America - Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern Univeristy
    • Zion, Illinois, United States, 60099
      • Cancer Treatment Centers of America - Chicago
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Siteman Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Next Virginia
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escalation Phase; 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; BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.
Experimental: Expansion Phase; 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; BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of BMF-219 monotherapy.	Safety and tolerability will be determined using treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) as outcomes.	46 months
To evaluate the pharmacokinetics of BMF-219.	Pharmacokinetics will be determined using maximum observed plasma concentration (Cmax ).	46 months
To evaluate the pharmacokinetics of BMF-219.	Pharmacokinetics will be determined time to maximum plasma concentration (tmax).	46 months
To evaluate the pharmacokinetics of BMF-219.	Pharmacokinetics will be determined using the AUC from time 0 to last quantifiable concentration (AUClast ).	46 months
To evaluate the efficacy of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.	Efficacy will be determined using duration of response (DOR), defined by the duration of time from the date of initial response of PR or better to the date of disease progression or death due to any cause, whichever occurs first. DOR will be assessed using RECIST 1.1 per investigator assessment.	46 months
To evaluate the efficacy of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.	Efficacy determined by disease control rate (DCR), defined as the proportion of response-evaluable subjects who maintain disease control (Complete Response, Partial Response or SD as per RECIST 1.1) from first dose through Week 6.	46 months

Collaborators and Investigators

• Sponsor: Biomea Fusion Inc.
• Investigators: Study Director: Steve Morris, MD, Biomea Fusion Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2023
• Primary Completion (Actual): January 15, 2025
• Study Completion (Actual): January 15, 2025

Study Registration Dates

• First Submitted: November 4, 2022
• First Submitted That Met QC Criteria: November 20, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Relapsed; Refractory; Metastatic; Unresectable; Locally Advanced; KRAS; Menin; Oral Covalent Menin Inhibitor; Irreversible Menin Inhibitor; Menin Inhibitor; Menin Therapy; KRAS Mutated
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Colorectal Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: COVALENT-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No