BMS-986490 + Bevacizumab for Cancer

Recruiting at 10 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bristol-Myers Squibb

Disqualifiers: Anaphylactic reactions, ILD/pneumonitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

360 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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 data supports the effectiveness of the drug Bevacizumab (Avastin) in treating cancer?

Research shows that Bevacizumab, when combined with chemotherapy, improves tumor response and progression-free survival (the time during which the cancer does not get worse) in patients with metastatic breast cancer and advanced colorectal cancer. It has also shown benefits in non-small-cell lung cancer and renal cell carcinoma. ^{1 2 3 4 5}

What safety information is available for Bevacizumab (Avastin) in cancer treatment?

Bevacizumab (Avastin) has been studied for safety in patients with metastatic colorectal cancer and advanced non-small cell lung cancer. It is generally considered safe, but some studies have noted risks of serious side effects, including cardiovascular issues, especially in older patients. ^{6 7 8 9 10}

What makes the drug BMS-986490 combined with Bevacizumab unique for cancer treatment?

BMS-986490 combined with Bevacizumab is unique because it targets specific pathways involved in cancer growth, potentially offering a novel approach compared to standard treatments. While Bevacizumab is known for inhibiting blood vessel growth in tumors, the specific role of BMS-986490 in this combination is not detailed in the available research, suggesting it may offer a new mechanism of action or benefit. ^{2 3 11 12 13}

What is the purpose of this trial?

This is a study of BMS-986490 as a monotherapy and in combination with bevacizumab in participants with select advanced solid tumors known to express CEACAM5.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for individuals with advanced solid tumors that express a specific protein called CEACAM5. The details about who can join or reasons why someone might not be eligible are not provided.

Inclusion Criteria

My colorectal cancer has worsened after treatment with 5-FU, irinotecan, or oxaliplatin.

My advanced cancer is confirmed and cannot be removed by surgery.

My NSCLC has worsened after 2 treatments and anti-PD-(L)1 therapy.

Exclusion Criteria

Other protocol-defined Inclusion/Exclusion criteria apply

History of anaphylactic reactions to irinotecan and/or bevacizumab

I have been treated before with drugs targeting CEACAM5.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986490 as a monotherapy or in combination with bevacizumab

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bevacizumab
• BMS-986490

Trial Overview The study is testing BMS-986490, both alone and combined with Bevacizumab, to see how well it works in treating certain advanced solid tumors.

Participant Groups

Group I: Part 2B Experimental Treatment 2 Interventions

Group II: Part 2A - Non-Small Cell Lung Cancer/Gastric Cancer (NSCLC/GC) Experimental Treatment 1 Intervention

Group III: Part 2A - Colorectal Cancer (CRC) Experimental Treatment 1 Intervention

Group IV: Part 1B Experimental Treatment 2 Interventions

Group V: Part 1A 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

In a study of 148 women with HER2-negative metastatic breast cancer, first-line therapy combining bevacizumab and chemotherapy resulted in a median progression-free survival (PFS) of 22.7 months and overall survival (OS) of 58.2 months, indicating its effectiveness in long-term treatment.

Patients who received maintenance hormonal therapy (MHT) experienced significantly longer PFS and OS, and those who had not been previously treated with taxanes also showed improved survival outcomes, suggesting that treatment history influences the efficacy of bevacizumab-based therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term response to first-line bevacizumab-based therapy in patients with metastatic breast cancer: results of the observational "LORENA" study. Redondo, A., Ramos Vázquez, M., Manso, L., et al.[2022]

In a phase III study involving 1,237 patients with HER2-negative metastatic breast cancer, the addition of bevacizumab (BV) to standard chemotherapy regimens significantly improved progression-free survival (PFS), with median PFS increasing from 5.7 to 8.6 months for capecitabine and from 8.0 to 9.2 months for taxane/anthracycline regimens.

Despite the improvement in PFS, there were no significant differences in overall survival (OS) between the BV and placebo groups, and the safety profile of BV was consistent with previous studies, indicating it is a safe addition to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. Robert, NJ., Diéras, V., Glaspy, J., et al.[2022]

In a study of 38 patients with metastatic breast cancer, the combination of erlotinib and bevacizumab was well-tolerated, with manageable side effects like diarrhea and skin rash, but showed limited effectiveness in terms of response rates.

Only one patient had a significant response lasting over 52 months, while the median time to disease progression was 11 weeks, indicating a need for better biomarkers to identify which patients might benefit from this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer. Dickler, MN., Rugo, HS., Eberle, CA., et al.[2021]

In a phase II trial involving 50 patients with resectable nonsquamous NSCLC, the addition of bevacizumab to neoadjuvant chemotherapy did not improve the rate of pathological downstaging, which was 38%.

The study found that new intratumoral cavitation occurred in 18% of patients treated with single-agent bevacizumab, suggesting it may serve as a potential biomarker for treatment response, particularly since no patients with KRAS-mutant tumors showed a pathologic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers. Chaft, JE., Rusch, V., Ginsberg, MS., et al.[2022]

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, has shown significant antitumor activity, particularly in renal cell carcinoma, where it extended the time to tumor progression compared to placebo.

In advanced colorectal cancer, adding bevacizumab to chemotherapy resulted in significantly longer overall survival and progression-free survival, indicating its effectiveness when combined with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the clinical development of bevacizumab. Chen, HX.[2019]

Bevacizumab (BV) added to chemotherapy for metastatic colorectal cancer significantly improves overall survival, progression-free survival, and response rates without causing clinically relevant increases in serious adverse events (SAE).

The risk of serious adverse events related to BV, such as wound healing complications and gastrointestinal perforation, remains low, especially if surgery is performed 5-6 weeks after BV treatment and a minimum of 28 days is allowed post-surgery before resuming BV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer. Hompes, D., Ruers, T.[2015]

In a study of 6803 colorectal cancer patients aged 65 and older, bevacizumab (BEV) was found to significantly increase the risk of arterial thromboembolic events (ATEs) by 82%, indicating a notable cardiovascular risk associated with its use.

However, there was no observed increase in the risk of cardiac death or cardiomyopathy/congestive heart failure, suggesting that while BEV does pose some cardiovascular risks, these may be lower than previously reported in clinical trials, possibly due to careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study. Tsai, HT., Marshall, JL., Weiss, SR., et al.[2022]

In a study of 60 metastatic colorectal cancer patients treated with bevacizumab and chemotherapy, the most common side effects were mild bleeding (28%) and hypertension (17%), indicating that while there are some toxicities, they are generally manageable.

Serious complications were rare, with only 5% of patients experiencing severe venous thromboembolic events and gastrointestinal perforation, suggesting that bevacizumab is well tolerated in combination with various chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of first-line bevacizumab in metastatic colorectal cancer. Akun, E., Okutur, K., Seber, S., et al.[2015]

A systematic review of 10 trials involving 5526 patients showed that bevacizumab biosimilars have comparable efficacy and safety to reference biologics in treating advanced non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (CRC).

The analysis indicated no significant differences in objective response rates, progression-free survival, or overall survival between bevacizumab biosimilars and standard treatments, suggesting that these biosimilars can be a viable alternative in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bevacizumab Biosimilars Compared With Reference Biologics in Advanced Non-small Cell Lung Cancer or Metastatic Colorectal Cancer Patients: A Network Meta-Analysis. Xu, X., Zhang, S., Xu, T., et al.[2022]

In a phase II study involving 131 patients with metastatic colorectal cancer, the combination of erlotinib with FOLFOX4 and bevacizumab significantly improved progression-free survival (PFS) to 9.6 months compared to 6.9 months for the FOLFOX4 and bevacizumab group.

While the combination treatment did not show a statistically significant difference in overall survival (OS), it resulted in a higher clinical response rate of 48.5% compared to 32.2% in the control group, although it was associated with a higher incidence of adverse events that were generally tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erlotinib in combination with bevacizumab and FOLFOX4 as second-line chemotherapy for patients with metastatic colorectal cancer. Shi, S., Lu, K., Gao, H., et al.[2020]

In a phase I study involving 19 patients with unresectable brain metastases, the combination of bevacizumab and whole-brain radiation therapy (WBRT) was found to be tolerable, with no dose-limiting toxicities reported.

At the highest dose level (15 mg/kg of bevacizumab), 6 out of 7 patients showed a response to treatment, including one complete response, suggesting that this regimen may be effective and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours. Lévy, C., Allouache, D., Lacroix, J., et al.[2022]

In a phase II trial involving 40 heavily pretreated patients with platinum-resistant ovarian cancer, the combination of bevacizumab and erlotinib showed clinical activity, with a disease control rate of 49% and a median progression-free survival (PFS) of 4 months.

The study found that high levels of tumor cell VEGF-A were associated with increased resistance to treatment, suggesting that VEGF-A may play a significant role in the tumor microenvironment and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpression of tumor vascular endothelial growth factor A may portend an increased likelihood of progression in a phase II trial of bevacizumab and erlotinib in resistant ovarian cancer. Chambers, SK., Clouser, MC., Baker, AF., et al.[2021]

In a study of 70 patients with newly diagnosed glioblastoma, combining bevacizumab (BV) with radiation therapy (RT) and temozolomide (TMZ) resulted in improved progression-free survival (PFS) of 13.6 months compared to 7.6 months in a control group, although overall survival (OS) was similar between groups.

The presence of MGMT promoter methylation in tumor tissue was associated with better OS and PFS, suggesting that this biomarker may help identify patients who could benefit more from the treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. Lai, A., Tran, A., Nghiemphu, PL., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Long-term response to first-line bevacizumab-based therapy in patients with metastatic breast cancer: results of the observational "LORENA" study. [2022]

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

RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. [2022]

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

A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer. [2021]

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

Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Expanding the clinical development of bevacizumab. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Review: incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study. [2022]

8. Cyprus pubmed.ncbi.nlm.nih.gov

Safety and tolerability of first-line bevacizumab in metastatic colorectal cancer. [2015]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bevacizumab Biosimilars Compared With Reference Biologics in Advanced Non-small Cell Lung Cancer or Metastatic Colorectal Cancer Patients: A Network Meta-Analysis. [2022]

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

Erlotinib in combination with bevacizumab and FOLFOX4 as second-line chemotherapy for patients with metastatic colorectal cancer. [2020]

11. England pubmed.ncbi.nlm.nih.gov

REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours. [2022]

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

Overexpression of tumor vascular endothelial growth factor A may portend an increased likelihood of progression in a phase II trial of bevacizumab and erlotinib in resistant ovarian cancer. [2021]

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

Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. [2022]