Clinical trial NCT05631574: Study of Covalent Menin Inhibitor BMF-219 in Adult Patients With KRAS Driven Non-Small Cell Lung Cancer, Pancreatic Cancer, and Colorectal Cancer
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: Biomea Fusion Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-30
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: To determine the OBDs/RP2Ds of BMF-219 monotherapy in subjects with KRAS-driven unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.
timeFrame: 30 months
measure: To determine the OBDs/RP2Ds of BMF-219 monotherapy in subjects with KRAS-driven unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.
timeFrame: 30 months
Secondary outcomes:
measure: To evaluate the safety and tolerability of BMF-219 monotherapy.
timeFrame: 46 months
measure: To evaluate the pharmacokinetics of BMF-219.
timeFrame: 46 months
measure: To evaluate the pharmacokinetics of BMF-219.
timeFrame: 46 months
measure: To evaluate the pharmacokinetics of BMF-219.
timeFrame: 46 months
measure: To evaluate the efficacy of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.
timeFrame: 46 months
measure: To evaluate the efficacy of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.
timeFrame: 46 months
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Cancer Treatment Centers of America - Phoenix
state: Arizona
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence (cCARE)
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Cancer Treatment Centers of America - Atlanta
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center of Northwestern Univeristy
state: Illinois
city: Zion
country: United States
facility: Cancer Treatment Centers of America - Chicago
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System - PPDS
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
Study officials:
affiliation: Biomea Fusion Inc.
name: Steve Morris, MD
role: STUDY_DIRECTOR
References: