BMS-986489 vs Atezolizumab for Small Cell Lung Cancer

Recruiting at 405 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Disqualifiers: Brain metastases, Lung diseases, Heart diseases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 weeks

530 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments to determine which is more effective for people with extensive-stage small cell lung cancer. One group receives a combination of BMS-986489 (an experimental treatment) with other drugs, while the other group receives Atezolizumab, a treatment already in use. The trial aims to compare the effectiveness and safety of these treatments. Individuals with this type of lung cancer who can still perform most daily activities independently might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BMS-986012, part of the BMS-986489 treatment, has been tested in people with small cell lung cancer. When combined with nivolumab, BMS-986012 appeared to slow the cancer's progress.

In earlier studies, patients tolerated BMS-986012 well, with tiredness and nausea as the most common side effects. These side effects are typical in cancer treatments. Importantly, no unexpected severe side effects were reported.

Atezolizumab, the other treatment being compared, is already approved for some cancers, including small cell lung cancer. Previous studies have shown that patients generally tolerate it well. Common side effects include tiredness and loss of appetite, which are typical for cancer treatments.

Overall, both treatments have been generally well-tolerated in past studies, with side effects similar to many cancer therapies. This suggests a reasonable safety profile for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of BMS-986012 and Nivolumab, known as BMS-986489, for treating small cell lung cancer because it introduces a novel approach compared to the standard treatments like chemotherapy and immune checkpoint inhibitors such as Atezolizumab. Most treatments for small cell lung cancer focus on broad strategies to attack cancer cells, but BMS-986489 works by enhancing the immune system's ability to recognize and destroy cancer cells through a targeted immune response. This combination leverages Nivolumab's ability to block the PD-1 pathway, potentially increasing the effectiveness of the immune system against cancer. By combining BMS-986012 with Nivolumab, researchers hope to offer a more precise and potent treatment option that could improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

This trial will compare BMS-986489 with Atezolizumab for treating small cell lung cancer. Studies have shown that combining Atezolizumab with carboplatin and etoposide can significantly improve overall survival for patients with extensive-stage small cell lung cancer (ES-SCLC). Initial findings suggest that BMS-986489, which includes BMS-986012 and nivolumab, shows promise. This treatment has demonstrated a modest benefit in delaying cancer progression and may also extend patient survival. Both treatments are under further study in this trial to better understand their effectiveness. ^{2 3 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for individuals with extensive-stage small cell lung cancer who are receiving their first line of therapy. Specific eligibility criteria details were not provided, so interested participants should inquire further to determine if they meet the necessary requirements.

Inclusion Criteria

I can do my normal activities with little or no help.

I have been diagnosed with extensive-stage small cell lung cancer.

I have a tumor outside the brain that can be measured by CT or MRI.

Exclusion Criteria

I have received treatments for advanced small cell lung cancer.

I have health issues like brain cancer spread, lung/heart disease, infections, other cancers, or nerve damage.

Other protocol-defined Inclusion/Exclusion criteria apply.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986489 (BMS-986012+Nivolumab Fixed Dose Combination) or Atezolizumab in combination with Carboplatin plus Etoposide as first-line therapy

6-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• BMS-986489 (BMS-986012+Nivolumab)

Trial Overview The study aims to compare a new treatment combination (BMS-986489, which includes Anti-fucosyl-GM1 and Nivolumab) with Carboplatin and Etoposide against an existing treatment (Atezolizumab) with the same chemotherapy drugs in patients with extensive-stage small cell lung cancer.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 3 Interventions

Group II: Arm B Active Control 3 Interventions

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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

Published Research Related to This Trial

Atezolizumab, a PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

Atezolizumab, an antibody targeting PD-L1, is effective as a second-line treatment for advanced non-small cell lung cancer (NSCLC), with case studies showing its use in patients with various genetic mutations, such as EGFR and ALK.

The treatment appears to provide clinical benefits even in patients with extensive metastases, suggesting that tumor mutational status and disease burden are important factors influencing the efficacy of atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Issues in the Use of Atezolizumab for Patients with Non-Small Cell Lung Cancer: Case Reports and Literature Review. Cobo, M., Rodríguez-Abreu, D., Pérez Parente, D., et al.[2021]

Atezolizumab is the first approved anti-PD-L1 inhibitor for treating squamous cell lung cancer (SqCLC) in patients who have experienced disease progression after initial therapies, highlighting its role in advanced stages of non-small cell lung cancer (NSCLC).

Current research is exploring atezolizumab's effectiveness in various treatment settings for SqCLC, indicating its potential for broader applications in future clinical scenarios, although specific target agents for this cancer subtype remain limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti PD-L1 antibody: is there a histologic-oriented efficacy? Focus on atezolizumab in squamous cell non-small cell lung cancer. Gemelli, M., Bidoli, P., Colonese, F., et al.[2022]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

In a phase 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

In a study of 158 patients with advanced non-small cell lung cancer, nivolumab showed a slightly higher objective response rate (22.5%) compared to atezolizumab (14.5%), but this difference was not statistically significant (p = 0.140).

Both treatments did not show significant differences in progression-free survival (PFS) and overall survival (OS), but atezolizumab had a more favorable safety profile, with fewer adverse events reported compared to nivolumab (49.3% vs. 76.4%, p < 0.001).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Analysis of Nivolumab and Atezolizumab Efficacy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer. Alonso-García, M., Sánchez-Gastaldo, A., Muñoz-Fuentes, MA., et al.[2023]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

Anti-PD-1/PD-L1 therapies (atezolizumab, pembrolizumab, nivolumab) significantly improve overall survival and progression-free survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC) compared to docetaxel, based on a review of 14 trials involving 3786 subjects.

For patients with EGFR wild-type NSCLC, anti-PD-1/PD-L1 therapy offers better survival outcomes than EGFR-TKIs, while for EGFR mutant patients, it is less effective than EGFR-TKIs in terms of progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer. Sheng, Z., Zhu, X., Sun, Y., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04702880

NCT04702880 | A Study of BMS-986012 in Combination ... The purpose of this study is to demonstrate that treatment with BMS-986012 in combination with carboplatin, etoposide, and nivolumab will have acceptable ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS8124

TIGOS-LS, an open-label, randomized study of BMS ... TIGOS-LS is an open-label, randomized study to evaluate the safety and efficacy of BMS-986489 as consolidation therapy vs the new standard durvalumab following ...

3. onclive.com onclive.com/view/frontline-bms-986012-plus-nivolumab-chemotherapy-shows-promise-in-es-sclc

Frontline BMS-986012 Plus Nivolumab/Chemotherapy ... BMS-986012 plus nivolumab and chemotherapy provided a modest PFS benefit but signals of OS improvement in extensive-stage small cell lung cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9579497/

BMS-986012, an Anti–Fucosyl-GM1 Monoclonal Antibody ... A phase 1/2, first-in-human study of BMS-986012 as monotherapy or in combination with nivolumab for adults with relapsed or refractory SCLC.

5. clinicaltrial.be clinicaltrial.be/en/details/455090?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study to Compare the Efficacy and Safety of BMS-986489... The Purpose of the Study is to Compare the Efficacy and Safety of BMS-986489 (Anti-fucosyl-GM1+ Nivolumab Fixed Dose Combination) in Combination with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06646276

NCT06646276 | A Study to Compare the Efficacy and ... The purpose of the study is to compare the efficacy and safety of BMS-986489 (Anti-fucosyl-GM1+ Nivolumab Fixed Dose Combination) in Combination with ...

7. careacross.com careacross.com/clinical-trials/trial/NCT06646276

A Study to Compare the Efficacy and Safety of BMS ... Summary: The Purpose of the Study is to Compare the Efficacy and Safety of BMS-986489 (Anti-fucosyl-GM1+ Nivolumab Fixed Dose Combination) in Combination with ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04702880

NCT04702880 | A Study of BMS-986012 in Combination ... The purpose of this study is to demonstrate that treatment with BMS-986012 in combination with carboplatin, etoposide, and nivolumab will have acceptable ...