BMS-986463 for Advanced Cancer

Recruiting at 10 trial locations

Overseen By BMS Study Connect www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bristol-Myers Squibb

Disqualifiers: Leptomeningeal metastases, Concurrent malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

240 Participants Needed

Trial Summary

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What makes the drug BMS-986463 unique for treating advanced cancer?

BMS-986463 is unique because it is a Bcl-2 inhibitor, which targets proteins that help cancer cells survive, potentially making it effective in combination with other treatments to enhance their effects. This approach is different from standard treatments that may not specifically target these survival proteins. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, and efficacy of escalating doses of BMS-986463 in participants with select advanced malignant tumors.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for individuals with certain advanced cancers, including uterine, ovarian, non-small cell lung cancer, and serous cystadenocarcinoma. Participants should be able to receive escalating doses of the study drug.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I have a tumor that can be biopsied in addition to the main one.

My cancer cannot be removed by surgery and has spread.

Exclusion Criteria

I do not have cancer spread to the lining of my brain and spinal cord.

I have no other cancers needing treatment or active cancers in the last 2 years.

I have not had radiation therapy in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of BMS-986463 to evaluate safety and tolerability

8-12 weeks

Dose Expansion

Participants receive expanded doses of BMS-986463 to further evaluate efficacy

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BMS-986463

Trial Overview The focus of this study is on BMS-986463. It's given in increasing amounts to see how safe it is and how well it works against specific advanced cancers.

Participant Groups

Group I: Arm 2: Dose Expansion Experimental Treatment 1 Intervention

Group II: Arm 1: Dose Escalation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

The BCL-2 antisense oligonucleotide (G3139) was generally well tolerated in a study of 35 patients with advanced cancer, although some experienced fatigue and temporary increases in liver enzymes at the highest dose of 6.9 mg/kg/day.

Pharmacokinetic analysis showed that G3139 reached steady-state plasma concentrations within 10 hours, but no major antitumor responses were observed; ongoing trials are now testing shorter infusion periods to potentially enhance its effectiveness alongside standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of BCL-2 antisense oligonucleotide (G3139) administered by continuous intravenous infusion in patients with advanced cancer. Morris, MJ., Tong, WP., Cordon-Cardo, C., et al.[2012]

In a phase I study involving 11 patients with advanced solid tumors, the combination of navitoclax and erlotinib was found to have a manageable safety profile, with common side effects including diarrhea, nausea, and vomiting, but no maximum tolerated dose was established.

Despite the lack of objective responses, the combination treatment resulted in a disease control rate of 27%, indicating some patients experienced stable disease, although the overall antitumor activity was limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with erlotinib in patients with advanced solid tumors. Tolcher, AW., LoRusso, P., Arzt, J., et al.[2018]

Primary tumor cells from acute lymphoblastic leukemia (ALL) showed high sensitivity to BH3 mimetic drugs ABT-263 and ABT-199, leading to rapid apoptotic cell death, indicating their potential as effective treatments.

The study revealed that these ALL cells were Bcl-2 dependent, and the primary cell cultures were more sensitive and uniform in response to BH3 mimetics compared to established cell lines, suggesting a promising model for preclinical drug testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BH3 Inhibitor Sensitivity and Bcl-2 Dependence in Primary Acute Lymphoblastic Leukemia Cells. Alford, SE., Kothari, A., Loeff, FC., et al.[2018]

Combining BRAF inhibitors (BRAFi) like vemurafenib or dabrafenib with the BCL-2 inhibitor navitoclax shows promise in enhancing treatment outcomes for patients with BRAF mutant tumors, as it synergistically reduces cancer cell viability in laboratory models.

In a study of 34 samples from 17 patients, early changes in anti-apoptotic protein levels were observed after BRAFi treatment, suggesting that targeting these proteins could help delay resistance and improve tumor regression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. Frederick, DT., Salas Fragomeni, RA., Schalck, A., et al.[2022]

The Bcl-2 inhibitor ABT-737 showed significant tumor regression in some small cell lung cancer (SCLC) cell line xenografts, but only limited effectiveness in primary SCLC xenografts, suggesting that primary tumors may have lower Bcl-2 expression or different characteristics affecting treatment response.

Combining ABT-737 with etoposide significantly enhanced tumor growth inhibition in primary SCLC xenografts, indicating that combination therapies may improve treatment outcomes for patients with SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer. Hann, CL., Daniel, VC., Sugar, EA., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I trial of BCL-2 antisense oligonucleotide (G3139) administered by continuous intravenous infusion in patients with advanced cancer. [2012]

2. Germany pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with erlotinib in patients with advanced solid tumors. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

BH3 Inhibitor Sensitivity and Bcl-2 Dependence in Primary Acute Lymphoblastic Leukemia Cells. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer. [2021]