BMF-219 for Lung Cancer

No longer recruiting at 44 trial locations

Overseen By Alex Cacovean, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Biomea Fusion Inc.

Must not be taking: CYP3A inhibitors/inducers

Disqualifiers: CNS metastasis, HIV, HCV, HBV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BMF-219 (a covalent menin inhibitor), to determine its effectiveness for certain advanced lung, pancreatic, or colorectal cancers. The study targets patients with a specific KRAS mutation, which makes standard therapies less effective. Participants may qualify if they have tried other treatments without success and have a type of cancer that cannot be surgically removed. The trial will explore different doses to identify the safest and most effective amount. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new drug.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you must stop all current medications. However, you cannot take strong or moderate CYP3A inhibitors/inducers during the trial.

Is there any evidence suggesting that BMF-219 is likely to be safe for humans?

Research shows that BMF-219, a new cancer treatment, has been tested for safety in people with certain cancers, such as lung, pancreatic, and colorectal cancer. Earlier studies tested different doses of BMF-219 to determine the safest and most effective amount. These studies did not find any major safety issues that would halt the trial. No serious side effects have been directly linked to the treatment, and the trial has continued without safety concerns. This suggests that BMF-219 is generally well-tolerated so far. However, since this research is still in the early stages, more information is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

BMF-219 is unique because it offers a new approach to treating lung cancer by targeting specific pathways involved in cancer cell growth. Unlike traditional treatments such as chemotherapy and radiation, which can affect both healthy and cancerous cells, BMF-219 is designed to home in on cancer cells more precisely, potentially reducing side effects. Researchers are excited about its novel mechanism of action, which could lead to improved effectiveness and better outcomes for patients with lung cancer.

What evidence suggests that this trial's treatment, BMF-219, could be effective for lung cancer?

Research shows that BMF-219, which participants in this trial will receive, is a promising treatment for lung cancer. It targets a protein called menin, which aids cancer growth. Earlier studies demonstrated that BMF-219 can potentially stop cancer cells from growing by blocking this protein. For cancers with KRAS mutations, such as non-small cell lung cancer (NSCLC), this method might be effective because these mutations often drive cancer growth. Early results suggest that BMF-219 could slow or halt tumor growth, offering hope for patients with advanced cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Steve Morris, MD

Principal Investigator

Biomea Fusion Inc.

Are You a Good Fit for This Trial?

Adults with advanced stages of NSCLC, PDAC, or CRC that can't be surgically removed and have KRAS mutations. They must have tried at least one systemic therapy before (up to four for NSCLC), be in a stable condition without serious infections or heart issues, not pregnant or breastfeeding, and willing to use birth control.

Inclusion Criteria

I am using effective birth control and will continue for 90 days after the trial ends.

My cancer has grown after 1-4 treatments, and side effects from past treatments are minimal.

I have advanced lung, pancreatic, or colorectal cancer with a specific KRAS mutation and no curative treatment options.

Exclusion Criteria

I have previously received menin inhibitor therapy.

I have serious heart disease or a known issue with my heart's electrical activity.

You have tested positive for HIV, HCV, or HBV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of BMF-219 to identify the Optimal Biologic Dose (OBD) and Recommended Phase 2 Dose (RP2D)

28-day cycles

Dose Expansion

Additional subjects are enrolled to further assess the safety and efficacy of BMF-219 at the OBD/RP2D

46 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMF-219

Trial Overview The trial is testing BMF-219's optimal dosages for safety and effectiveness. It targets adults with specific types of cancer (NSCLC, PDAC, CRC) that are linked to KRAS gene changes. The study will find the right dose by starting low and adjusting as needed.

How Is the Trial Designed?

Group I: Expansion Phase Experimental Treatment 1 Intervention

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.

Group II: Escalation Phase Experimental Treatment 1 Intervention

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).

Who Is Running the Clinical Trial?

Biomea Fusion Inc.

Lead Sponsor

Trials

5

Recruited

780+

Published Research Related to This Trial

In a study involving 28 patients with advanced biliary tract cancer, binimetinib was found to be well tolerated, with common mild side effects like rash (82%) and nausea (54%), and only two patients experienced severe adverse events.

Binimetinib demonstrated promising clinical activity, with 43% of patients achieving stable disease and two patients showing objective responses, including one complete response, suggesting its potential effectiveness in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer. Finn, RS., Ahn, DH., Javle, MM., et al.[2019]

In a phase II study involving 75 patients with non-small cell lung cancer (NSCLC), maintenance treatment with vandetanib after chemotherapy showed a progression-free survival (PFS) rate of 44.4% at 3 months, which supports its efficacy compared to a placebo.

Vandetanib was generally well tolerated, with common side effects including rash (77.3%) and diarrhea (60.0%), indicating a manageable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, phase II study of vandetanib maintenance for advanced or metastatic non-small-cell lung cancer following first-line platinum-doublet chemotherapy. Ahn, JS., Lee, KH., Sun, JM., et al.[2022]

The phase I study found that the MEK inhibitor binimetinib, when combined with carboplatin and pemetrexed, has a recommended phase II dose of 30 mg BID and shows manageable toxicity, with 61.5% of patients experiencing grade 3/4 adverse events.

The treatment demonstrated promising efficacy, with a 50% objective response rate and an 83.3% disease control rate in patients with advanced non-squamous NSCLC, particularly in those with KRAS/NRAS mutations, who had a higher response rate of 62.5%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer. Fung, AS., Graham, DM., Chen, EX., et al.[2021]

The PHAROS trial is investigating the combination of the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib in patients with metastatic non-small-cell lung cancer (NSCLC) that have BRAFV600 mutations, which occur in 1-2% of NSCLC cases.

The primary goal of the trial is to assess the objective response rate to this treatment, with results expected to provide insights into both the effectiveness and safety of this combination therapy for patients with these specific mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encorafenib plus binimetinib in patients with BRAFV600-mutant non-small cell lung cancer: phase II PHAROS study design. Riely, GJ., Ahn, MJ., Felip, E., et al.[2022]

The combination of encorafenib and binimetinib was found to be safe and showed promising activity in patients with BRAF V600E-mutant solid tumors, with a recommended phase 2 dose established for further studies.

In phase II, the treatment resulted in confirmed responses in 67% of BRAFi-naïve melanoma patients, indicating significant efficacy, while the most common serious side effect was increased alanine aminotransferase levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors. Sullivan, RJ., Weber, J., Patel, S., et al.[2021]

In a phase I study involving 26 patients with metastatic colorectal cancer, the combination of oral binimetinib and FOLFOX was found to have a maximum tolerated dose of 45 mg taken twice daily, with no dose-limiting toxicities observed.

The treatment showed some antitumor activity, with 9 out of 13 patients on continuous dosing achieving stable disease after 2 months, and a median progression-free survival of 3.5 months, indicating potential efficacy in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial of binimetinib in combination with FOLFOX in patients with advanced metastatic colorectal cancer who failed prior standard therapy. Cho, M., Gong, J., Frankel, P., et al.[2022]

In a phase 1B trial involving 18 patients with advanced NSCLC and KRAS mutations, the combination of the MEK-inhibitor binimetinib with cisplatin and pemetrexed showed no unexpected toxicity, indicating a favorable safety profile for this treatment regimen.

The overall response rate was 33% among patients receiving the maximum tolerated dose of binimetinib, with a median progression-free survival of 5.7 months, suggesting limited early antitumor activity when combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binimetinib, pemetrexed and cisplatin, followed by maintenance of binimetinib and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) and KRAS mutations. The phase 1B SAKK 19/16 trial. Froesch, P., Mark, M., Rothschild, SI., et al.[2021]

Icotinib, an oral EGFR inhibitor, showed an overall response rate of 37.6% and a disease control rate of 79.2% in 101 patients with advanced non-small cell lung cancer, indicating its efficacy in this population.

The treatment was well-tolerated, with common side effects being rash (35.6%) and diarrhea (17.8%), and patients with EGFR mutations experienced better progression-free survival compared to those without these mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Icotinib treatment in patients with stage IIIb/IV non-small cell lung cancer. Qin, N., Yang, X., Zhang, Q., et al.[2018]

In a phase II study involving 98 patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC), the combination of encorafenib and binimetinib achieved a confirmed objective response rate of 75% in treatment-naïve patients and 46% in previously treated patients, indicating significant efficacy.

The treatment was generally well-tolerated, with common side effects including nausea (50%) and diarrhea (43%), but it also led to dose reductions in 24% of patients and one serious adverse event of intracranial hemorrhage, highlighting the importance of monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. Riely, GJ., Smit, EF., Ahn, MJ., et al.[2023]

Vandetanib, an oral inhibitor targeting both VEGFR and EGFR, shows anti-tumor activity in advanced non-small-cell lung cancer (NSCLC) with improved disease control and objective responses.

Despite its activity, Phase III clinical trials revealed that vandetanib did not provide a significant overall survival benefit, leading to its discontinuation in further development for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vandetanib for the treatment of non-small-cell lung cancer. Wong, HL., de Boer, RH.[2022]

In a study of 46 treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer, alternating therapy with osimertinib and afatinib resulted in a median progression-free survival of 21.3 months, indicating promising efficacy despite not meeting the primary endpoint of 12-month progression-free survival probability.

The treatment was generally well-tolerated, with common side effects including diarrhea (73.9%) and rash (63.0%), and only a few cases of serious pneumonitis, suggesting a manageable safety profile for this alternating therapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L). Hayashi, H., Yonesaka, K., Nakamura, A., et al.[2022]

Citations

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NCT05631574 | Study of Covalent Menin Inhibitor BMF- ... 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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COVALENT-102: A phase 1/1b dose finding study of BMF- ... Following dose-escalation, each indication will enroll patients in expansion cohorts independently to obtain further safety and efficacy data.

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A Phase 1/1b Study of BMF-219, A Menin Inhibitor ... COVALENT-102 is an open-label, multicenter, dose finding study evaluating the safety, tolerability, and clinical activity of escalating doses of BMF-219.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1556086423014405

A Phase 1/1b Study of BMF-219, A Menin Inhibitor in ... COVALENT-102 is an open-label, multicenter, dose finding study evaluating the safety, tolerability, and clinical activity of escalating doses of BMF-219.

5. georgiacancerinfo.org georgiacancerinfo.org/clinical-trials/detail/5642

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

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