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

Primary Purpose

Non Small Cell Lung Cancer, Pancreatic Cancer, Colorectal Cancer

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BMF-219
Sponsored by
Biomea Fusion Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Oral Covalent Menin Inhibitor, Relapsed, Refractory, Irreversible Menin Inhibitor, Menin Inhibitor, Unresectable, Locally Advanced, Metastatic, Menin, Menin Therapy, KRAS, KRAS Mutated

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria 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 Exclusion Criteria 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.

Sites / Locations

  • Cancer Treatment Centers of America - PhoenixRecruiting
  • California Cancer Associates for Research and Excellence (cCARE)Recruiting
  • University of California, San Diego
  • Sarah Cannon Research Institute at HealthONE
  • Mount Sinai Medical Center
  • Cancer Treatment Centers of America - AtlantaRecruiting
  • Robert H. Lurie Comprehensive Cancer Center of Northwestern Univeristy
  • Cancer Treatment Centers of America - ChicagoRecruiting
  • Mayo Clinic
  • Washington University School of Medicine - Siteman Cancer CenterRecruiting
  • University of Nebraska Medical Center
  • Roswell Park Cancer InstituteRecruiting
  • Ohio State University
  • Tennessee Oncology
  • Vanderbilt Ingram Cancer Center
  • The University of Texas MD Anderson Cancer CenterRecruiting
  • NEXT OncologyRecruiting
  • NEXT VirginiaRecruiting
  • Fred Hutchinson Cancer CenterRecruiting
  • Samsung Medical Center
  • Seoul National University Hospital
  • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Severance Hospital Yonsei University Health System - PPDS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Escalation Phase

Expansion Phase

Arm 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).

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
To evaluate the pharmacokinetics of BMF-219.
Pharmacokinetics will be determined using maximum observed plasma concentration (Cmax ).
To evaluate the pharmacokinetics of BMF-219.
Pharmacokinetics will be determined time to maximum plasma concentration (tmax).
To evaluate the pharmacokinetics of BMF-219.
Pharmacokinetics will be determined using the AUC from time 0 to last quantifiable concentration (AUClast ).
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.
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.

Full Information

First Posted
November 4, 2022
Last Updated
August 30, 2023
Sponsor
Biomea Fusion Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05631574
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 12, 2023 (Actual)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biomea Fusion Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Escalation Phase
Arm Type
Experimental
Arm 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).
Arm Title
Expansion Phase
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
BMF-219
Intervention Description
BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.
Primary Outcome Measure Information:
Title
To determine the OBDs/RP2Ds of BMF-219 monotherapy in subjects with KRAS-driven unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.
Description
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.
Time Frame
30 months
Title
To determine the OBDs/RP2Ds of BMF-219 monotherapy in subjects with KRAS-driven unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.
Description
OBD/RP2D as measured by objective response rate (ORR). ORR will be assessed using RECIST 1.1 per investigator assessment.
Time Frame
30 months
Secondary Outcome Measure Information:
Title
To evaluate the safety and tolerability of BMF-219 monotherapy.
Description
Safety and tolerability will be determined using treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) as outcomes.
Time Frame
46 months
Title
To evaluate the pharmacokinetics of BMF-219.
Description
Pharmacokinetics will be determined using maximum observed plasma concentration (Cmax ).
Time Frame
46 months
Title
To evaluate the pharmacokinetics of BMF-219.
Description
Pharmacokinetics will be determined time to maximum plasma concentration (tmax).
Time Frame
46 months
Title
To evaluate the pharmacokinetics of BMF-219.
Description
Pharmacokinetics will be determined using the AUC from time 0 to last quantifiable concentration (AUClast ).
Time Frame
46 months
Title
To evaluate the efficacy of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.
Description
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.
Time Frame
46 months
Title
To evaluate the efficacy of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC.
Description
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.
Time Frame
46 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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 Exclusion Criteria 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alex Cacovean, MD
Phone
1-844-245-0490
Email
clinicaltrials@biomeafusion.com
First Name & Middle Initial & Last Name or Official Title & Degree
Tracy Tong
Phone
1-844-245-0490
Email
clinicaltrials@biomeafusion.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan Morris, MD
Organizational Affiliation
Biomea Fusion Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Cancer Treatment Centers of America - Phoenix
City
Goodyear
State/Province
Arizona
ZIP/Postal Code
85338
Country
United States
Individual Site Status
Recruiting
Facility Name
California Cancer Associates for Research and Excellence (cCARE)
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California, San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Sarah Cannon Research Institute at HealthONE
City
Denver
State/Province
Colorado
ZIP/Postal Code
80237
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Mount Sinai Medical Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Cancer Treatment Centers of America - Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30269
Country
United States
Individual Site Status
Recruiting
Facility Name
Robert H. Lurie Comprehensive Cancer Center of Northwestern Univeristy
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Cancer Treatment Centers of America - Chicago
City
Zion
State/Province
Illinois
ZIP/Postal Code
60099
Country
United States
Individual Site Status
Recruiting
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Washington University School of Medicine - Siteman Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Individual Site Status
Recruiting
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Vanderbilt Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
NEXT Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
NEXT Virginia
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Name
Fred Hutchinson Cancer Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Name
Samsung Medical Center
City
Gangnam-Gu
State/Province
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Name
Seoul National University Hospital
City
Jongno-gu
State/Province
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Name
The Catholic University of Korea, Seoul St. Mary's Hospital
City
Seocho-gu
State/Province
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Name
Severance Hospital Yonsei University Health System - PPDS
City
Seodaemun-gu
State/Province
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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