Study of Covalent Menin Inhibitor BMF-219 in Adult Patients With KRAS Driven Non-Small Cell Lung Cancer, Pancreatic Cancer, and Colorectal Cancer
Study Details
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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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.
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Outcome Measures
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. [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. [30 months]
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. [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. [46 months]
Pharmacokinetics will be determined using maximum observed plasma concentration (Cmax ).
- To evaluate the pharmacokinetics of BMF-219. [46 months]
Pharmacokinetics will be determined time to maximum plasma concentration (tmax).
- To evaluate the pharmacokinetics of BMF-219. [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. [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. [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.
Eligibility Criteria
Criteria
Inclusion Criteria
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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)
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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
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ECOG PS of 0-2 (0-1 for PDAC) and a life expectancy > 3 months in the opinion of the Investigator
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Adequate hematological, liver, and renal function
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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
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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
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Serious concomitant disorder including infection
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Known positive test for HIV, HCV, HBV surface antigen
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Concurrent malignancy in the previous 2 years
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Prior menin therapy
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Requiring treatment with a strong or moderate CYP3A inhibitor/inducer
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Significant cardiovascular disease or QTcF or QTcB prolongation.
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Major surgery within 4 weeks prior to first dose
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Women who are pregnant or lactating.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | CTCA Clinical Research, LLC | Goodyear | Arizona | United States | 85338 |
2 | California Cancer Care Associates | Encinitas | California | United States | 92024 |
3 | University of California, San Diego | La Jolla | California | United States | 92037 |
4 | CTCA Clinical Research, LLC | Zion | Illinois | United States | 60099 |
5 | Washington University School of Medicine in St. Louis | Saint Louis | Missouri | United States | 63110 |
6 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14203 |
7 | Ohio State Univeristy | Columbus | Ohio | United States | 43210 |
8 | MD Anderson | Houston | Texas | United States | 77030 |
9 | NEXT Oncology | San Antonio | Texas | United States | 78229 |
10 | NEXT Virginia | Fairfax | Virginia | United States | 22031 |
11 | Fred Hutch, University of Washington | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Biomea Fusion Inc.
Investigators
- Study Director: Stephan Morris, MD, Biomea Fusion Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- COVALENT-102