Colorectal Cancer, CRC, KRAS Mutation-Related Tumors, Non Small Cell Lung Cancer, NSCLC, Pancreatic Cancer, 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
Conditions
Keywords
Oral Covalent Menin Inhibitor, Relapsed, Refractory, Irreversible Menin Inhibitor, Menin Inhibitor, Unresectable, Locally Advanced, Metastatic, Menin, Menin Therapy, KRAS, KRAS Mutated
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.
Interventions
DRUGBMF-219
BMF-219 is an orally bioavailable, covalent small-molecule menin inhibitor.
Sponsors
Biomea Fusion Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
Countries
South Korea, United States
Outcome results
None listed