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

Colorectal Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05631574
• Other study ID #: COVALENT-102
• Status: Recruiting
• Phase: Phase 1
• Start date: January 12, 2023
• Est. completion date: October 2026

Study information

• Verified date: December 2023
• Source: Biomea Fusion Inc.
• Contact: Alex Cacovean, MD
• Phone: 1-844-245-0490
• Email: clinicaltrials[@]biomeafusion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: October 2026
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Gangnam-Gu	Seoul
Korea, Republic of	Seoul National University Hospital	Jongno-gu	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seocho-gu	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System - PPDS	Seodaemun-gu	Seoul
United States	Cancer Treatment Centers of America - Atlanta	Atlanta	Georgia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Robert H. Lurie Comprehensive Cancer Center of Northwestern Univeristy	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	California Cancer Associates for Research and Excellence (cCARE)	Encinitas	California
United States	NEXT Virginia	Fairfax	Virginia
United States	Cancer Treatment Centers of America - Phoenix	Goodyear	Arizona
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California, San Diego	La Jolla	California
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri
United States	NEXT Oncology	San Antonio	Texas
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Cancer Treatment Centers of America - Chicago	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Biomea Fusion Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	To evaluate the pharmacokinetics of BMF-219.	Pharmacokinetics will be determined using maximum observed plasma concentration (Cmax ).	46 months
Secondary	To evaluate the pharmacokinetics of BMF-219.	Pharmacokinetics will be determined time to maximum plasma concentration (tmax).	46 months
Secondary	To evaluate the pharmacokinetics of BMF-219.	Pharmacokinetics will be determined using the AUC from time 0 to last quantifiable concentration (AUClast ).	46 months
Secondary	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
Secondary	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