Relatlimab + Nivolumab + Chemotherapy for Lung Cancer

Not currently recruiting at 345 trial locations

Overseen By BMS Study Connect Contact Center http://www.bmsstudyconnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bristol-Myers Squibb

Must not be taking: EGFR inhibitors, ALK inhibitors

Disqualifiers: EGFR mutations, ALK mutations, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for individuals with Stage IV or recurrent non-small cell lung cancer (NSCLC) who have not received prior treatments. Researchers aim to determine if adding two immunotherapy drugs, relatlimab and nivolumab, to standard chemotherapy can enhance treatment outcomes and ensure safety. Participants may qualify if they have advanced NSCLC untreated by other cancer drugs. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that participants should not have had prior systemic anti-cancer treatment for advanced or metastatic disease.

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

Research has shown that combining the drugs relatlimab and nivolumab with platinum doublet chemotherapy (PDCT) is generally well-tolerated. Studies indicate that the safety profile of this combination aligns with what is known about each drug individually.

In previous studies, 54% of patients experienced serious side effects (grade 3 or 4) related to the treatment. This indicates that more than half of the participants faced significant side effects, a common occurrence in cancer treatments. However, these findings suggest that the combination is relatively safe, as the side effects are similar to those of other treatments.

Both nivolumab and relatlimab have approval for other conditions, further supporting their safety. For those considering joining a trial, it may be reassuring to know that many patients have already used these drugs safely in other contexts. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Relatlimab and Nivolumab for lung cancer treatment because it offers a unique approach by targeting multiple immune pathways simultaneously. Unlike standard chemotherapy, which directly attacks cancer cells, these drugs enhance the body's immune response to fight cancer more effectively. Relatlimab targets the LAG-3 protein, while Nivolumab targets the PD-1 protein, both of which are responsible for dampening the immune response. By blocking these proteins, the treatment can potentially allow the immune system to better recognize and destroy cancer cells. This novel combination could lead to improved outcomes for patients compared to traditional treatments alone.

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

Research shows that combining the drugs relatlimab and nivolumab with chemotherapy can help treat lung cancer. In this trial, participants will receive different combinations of these treatments. Some will receive nivolumab with relatlimab at varying doses alongside Platinum Doublet Chemotherapy (PDCT), while others will receive nivolumab with PDCT alone. Earlier studies demonstrated that adding relatlimab to nivolumab and chemotherapy benefited patients with advanced non-small cell lung cancer (NSCLC). These patients experienced better outcomes compared to those who received standard treatments. Specifically, patients on this combination went twice as long without their cancer worsening. This suggests that the combination could effectively manage NSCLC. ^{1 2 4 5 6}

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 adults with Stage IV or recurrent non-small cell lung cancer (NSCLC) who haven't had systemic anti-cancer treatment for advanced disease. They should have a good performance status, meaning they're fairly active and can care for themselves. People with certain gene mutations treatable by targeted therapy, untreated brain metastases, another active cancer, or previous immunotherapy are excluded.

Inclusion Criteria

I am fully active or have some restrictions but can still care for myself.

I haven't received any systemic anti-cancer treatments for my advanced cancer.

My lung cancer is confirmed to be advanced or has come back and is either SQ or NSQ type.

Exclusion Criteria

My cancer has specific mutations (EGFR, ALK, ROS-1, BRAF V600E) treatable with targeted therapy.

I have previously been treated with specific immunotherapy drugs.

My cancer has spread to the lining of my brain and spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Relatlimab plus Nivolumab in combination with platinum doublet chemotherapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days post last dose

Long-term Follow-up

Participants are monitored for long-term outcomes and adverse events

Approximately 32.8 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Nivolumab
• Pemetrexed
• Relatlimab

Trial Overview The study tests the effectiveness of Relatlimab combined with Nivolumab and chemotherapy versus just Nivolumab with chemotherapy in treating NSCLC. It aims to see if adding Relatlimab improves response rates compared to the current standard which includes Nivolumab.

How Is the Trial Designed?

Group I: Part 2: Arm C (Nivolumab + Relatlimab Dose 2 + PDCT) Experimental Treatment 6 Interventions

Group II: Part 1: Arm B (Nivolumab + Relatlimab Dose 2 + PDCT)) Experimental Treatment 7 Interventions

Group III: Part 1: Arm A (Nivolumab + Relatlimab Dose 1 + Platinum Doublet Chemotherapy (PDCT)) Experimental Treatment 7 Interventions

Group IV: Part 2: Arm D (Nivolumab + PDCT) Active Control 5 Interventions

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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

Pemetrexed (Alimta) is an effective treatment for mesothelioma and shows comparable survival rates to docetaxel in advanced non-small-cell lung cancer (NSCLC) while causing significantly fewer and less severe side effects.

In combination with platinum agents, pemetrexed has demonstrated significant activity and a favorable toxicity profile, making it a promising option for treating thoracic malignancies and warranting further research with other novel drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced NSCLC: a review of the clinical data. Zinner, RG., Fossella, FV., Herbst, RS.[2015]

In a study of 109 patients with advanced non-squamous non-small cell lung cancer, the combination of pemetrexed and carboplatin followed by pemetrexed maintenance showed similar efficacy in elderly patients (≥70 years) compared to younger patients, with median progression-free survival of 5.2 months for the elderly versus 5.8 months for younger patients.

While elderly patients experienced more frequent grade 3/4 hematologic toxicities, these were manageable through dose adjustments, and non-hematologic toxicities were similar to those seen in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients. Nogami, N., Nishio, M., Okamoto, I., et al.[2022]

In a phase II clinical study involving 102 patients with malignant pleural mesothelioma, the combination of pemetrexed and carboplatin resulted in an objective response rate of 18.6%, with 65.7% of patients achieving disease control.

The treatment was well tolerated, with mild toxicity reported; grade 3 or 4 neutropenia occurred in 9.7% of cycles, and the median overall survival was 12.7 months, suggesting that this combination could be a viable alternative to the standard treatment with pemetrexed and cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. Ceresoli, GL., Zucali, PA., Favaretto, AG., et al.[2022]

In a study involving 361 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed and carboplatin (Pem+Cb) did not show a significant advantage in progression-free survival without grade 4 toxicity compared to paclitaxel, carboplatin, and bevacizumab (Pac+Cb+Bev).

While both treatment regimens were generally well tolerated, Pem+Cb was associated with higher rates of grade 3/4 anemia and thrombocytopenia, whereas Pac+Cb+Bev had more cases of grade 3/4 neutropenia and alopecia, indicating differing toxicity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. Zinner, RG., Obasaju, CK., Spigel, DR., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

A systematic review of 45 studies involving 16,141 cases found that various platinum-based chemotherapy regimens for incurable non-small cell lung cancer (NSCLC) did not show significant differences in overall survival rates, indicating that multiple regimens can be considered effective.

Specifically, regimens like Carboplatin plus Paclitaxel and Bevacizumab were used as a common comparator, and other combinations such as Cisplatin plus Tegafur gimeracil oteracil and Carboplatin plus S1 were also found to be acceptable first-choice treatments without significantly poorer survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The best platinum regimens for chemo-naive incurable non-small cell lung cancer: network meta-analysis. Horita, N., Nagashima, A., Nakashima, K., et al.[2022]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

The study evaluated the safety and tolerability of carboplatin and pemetrexed in 20 elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, finding that the recommended dose was carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m², with manageable toxicities.

The treatment resulted in a 30% overall response rate, with a median progression-free survival of 4.8 months, indicating that this combination therapy is both effective and tolerable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer. Takeoka, H., Yamada, K., Azuma, K., et al.[2018]

In a study of 42 lung cancer patients receiving pemetrexed plus carboplatin, 19% experienced severe hematologic toxicities during the first cycle of chemotherapy, highlighting the significant risk associated with this treatment regimen.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) was found to significantly increase the risk of severe hematologic toxicities, suggesting that drug interactions may play a critical role in the toxicity experienced by patients, rather than renal function alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-steroidal anti-inflammatory drugs induce severe hematologic toxicities in lung cancer patients receiving pemetrexed plus carboplatin: A retrospective cohort study. Kawazoe, H., Yano, A., Ishida, Y., et al.[2022]

In a study of 108 patients with advanced non-squamous non-small cell lung cancer (NSCLC), adding bevacizumab to pemetrexed as maintenance therapy significantly improved progression-free survival (PFS) compared to pemetrexed alone, with PFS of 7.0 months versus 5.4 months.

Patients who responded partially to initial treatment had a median overall survival of 29.6 months with the addition of bevacizumab, compared to 23.3 months with pemetrexed alone, suggesting a potential survival benefit from the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Phase II study of pemetrexed plus bevacizumab versus pemetrexed alone after treatment with cisplatin, pemetrexed, and bevacizumab in advanced non-squamous, non-small cell lung cancer: TORG (thoracic oncology research group) 1321. Kasai, T., Mori, K., Nakamura, Y., et al.[2023]

In a study of 53 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, treatment with pemetrexed plus cisplatin or carboplatin resulted in a median overall survival of 10 months and a median progression-free survival of 6 months.

The treatment was generally well-tolerated, with only a small percentage of patients experiencing severe side effects, such as grade 3 or 4 leukopenia and thrombocytopenia, indicating that pemetrexed combined with platinum-based drugs can be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. Zhang, GZ., Jiao, SC., Meng, ZT.[2021]

In a study involving 1669 patients with non-small cell lung cancer (NSCLC), treatment with cisplatin and pemetrexed resulted in significantly longer survival without severe drug-related toxicity compared to cisplatin and gemcitabine, indicating a better clinical benefit-to-risk profile.

For patients with non-squamous NSCLC, cisplatin and pemetrexed not only improved survival without grade 3 or 4 toxicity but also showed superior outcomes in terms of survival without grade 4 toxicity, highlighting its effectiveness and tolerability in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival without toxicity for cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemonaïve patients with advanced non-small cell lung cancer: a risk-benefit analysis of a large phase III study. Scagliotti, GV., Park, K., Patil, S., et al.[2022]

Citations

1. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Provides-Update-on-Phase-3-RELATIVITY-098-Trial/default.aspx

Bristol Myers Squibb Provides Update on Phase 3 ... RELATIVITY-098 is a randomized Phase 3, double-blind study evaluating adjuvant immunotherapy with Opdualag, the fixed-dose combination of nivolumab and ...

2. opdualaghcp.com opdualaghcp.com/efficacy/melanoma/relativity-047

Efficacy | Opdualag® (nivolumab and relatlimab-rmbw) for HCPs All data shown below is 4-year data based on minimum potential follow-up of 45.3 months.2. Overall survival at 4 years ( ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04623775

NCT04623775 | A Study of Relatlimab Plus Nivolumab in ... The purpose of this study is to assess the safety profile of relatlimab plus nivolumab in combination with platinum doublet chemotherapy (PDCT) and to ...

4. onclive.com onclive.com/view/relatlimab-plus-nivolumab-and-chemo-improves-clinical-benefit-in-stage-iv-nsclc

Relatlimab Plus Nivolumab and Chemo Improves Clinical ... Findings from the phase 2 RELATIVITY-104 study demonstrates a clinical benefit with the addition of relatlimab to nivolumab and chemotherapy.

5. opdualag.com opdualag.com/about/results

Advanced Melanoma Clinical Trial Results Half the patients on Opdualag went 2X longer without advanced melanoma worsening than those on a standard treatment. In a clinical trial of 714 patients ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602507/

Nivolumab and Relatlimab (Opdualag) - NCBI Bookshelf - NIH The objective of the safety outcomes was to assess the overall safety and tolerability of nivolumab-relatlimab and nivolumab. Safety data reported in this ...