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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

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ClinicalTrials.gov Identifier: NCT05631574
Recruitment Status : Recruiting
First Posted : November 30, 2022
Last Update Posted : December 26, 2023
Sponsor:
Information provided by (Responsible Party):
Biomea Fusion Inc.

Tracking Information
First Submitted Date  ICMJE November 4, 2022
First Posted Date  ICMJE November 30, 2022
Last Update Posted Date December 26, 2023
Actual Study Start Date  ICMJE January 12, 2023
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 23, 2022)
  • To determine the OBDs/RP2Ds of BMF-219 monotherapy in subjects with KRAS-driven unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC. [ Time Frame: 30 months ]
    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. [ Time Frame: 30 months ]
    OBD/RP2D as measured by objective response rate (ORR). ORR will be assessed using RECIST 1.1 per investigator assessment.
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2022)
  • To determine the OBDs/RP2Ds of BMF-219 monotherapy in subjects with unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC. [ Time Frame: 30 months ]
    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 unresectable, locally advanced, or metastatic NSCLC, PDAC and CRC. [ Time Frame: 30 months ]
    OBD/RP2D as measured by objective response rate (ORR). ORR will be assessed using RECIST 1.1 per investigator assessment.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2022)
  • To evaluate the safety and tolerability of BMF-219 monotherapy. [ Time Frame: 46 months ]
    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. [ Time Frame: 46 months ]
    Pharmacokinetics will be determined using maximum observed plasma concentration (Cmax ).
  • To evaluate the pharmacokinetics of BMF-219. [ Time Frame: 46 months ]
    Pharmacokinetics will be determined time to maximum plasma concentration (tmax).
  • To evaluate the pharmacokinetics of BMF-219. [ Time Frame: 46 months ]
    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. [ Time Frame: 46 months ]
    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. [ Time Frame: 46 months ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Drug: BMF-219
BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.
Study Arms  ICMJE
  • 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).

    Intervention: Drug: BMF-219
  • 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.

    Intervention: Drug: BMF-219
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2022)		 90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2026
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alex Cacovean, MD 1-844-245-0490 clinicaltrials@biomeafusion.com
Contact: Tracy Tong 1-844-245-0490 clinicaltrials@biomeafusion.com
Listed Location Countries  ICMJE Korea, Republic of,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05631574
Other Study ID Numbers  ICMJE COVALENT-102
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Biomea Fusion Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Biomea Fusion Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Stephan Morris, MD Biomea Fusion Inc.
PRS Account Biomea Fusion Inc.
Verification Date December 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP