Relatlimab + Nivolumab + Chemotherapy for Lung Cancer

Recruiting at 318 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

468 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment combining two immunotherapy drugs (relatlimab and nivolumab) with standard chemotherapy. It targets patients with advanced or recurrent lung cancer. The goal is to see if this combination improves outcomes compared to using just one immunotherapy drug with chemotherapy. Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy.

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.

What data supports the effectiveness of the drug combination Relatlimab + Nivolumab + Chemotherapy for Lung Cancer?

Research shows that combining pemetrexed with cisplatin or carboplatin is effective in treating advanced non-small cell lung cancer (NSCLC), and this combination is well-tolerated compared to other regimens. This suggests that the chemotherapy component of the treatment may be effective for lung cancer. ^{1 2 3 4 5}

Is the combination of Relatlimab, Nivolumab, and Chemotherapy safe for humans?

Studies have shown that the combination of pemetrexed and carboplatin or cisplatin is generally safe and well-tolerated in patients with advanced lung cancer, including elderly patients. However, severe blood-related side effects can occur, especially when combined with certain pain relievers. The combination of cisplatin and pemetrexed is also noted for better tolerability compared to other treatments. ^{1 4 6 7 8}

What makes the Relatlimab + Nivolumab + Chemotherapy treatment unique for lung cancer?

This treatment combines Relatlimab and Nivolumab, which are immune checkpoint inhibitors that help the immune system attack cancer cells, with traditional chemotherapy drugs like Carboplatin and Pemetrexed. This combination aims to enhance the effectiveness of chemotherapy by also engaging the body's immune response, offering a novel approach compared to standard chemotherapy alone. ^{5 9 10 11 12}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 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 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]

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 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]

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 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]

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]

References

1. England 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. [2022]

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

Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The best platinum regimens for chemo-naive incurable non-small cell lung cancer: network meta-analysis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. [2021]

5. United States 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. [2022]

6. Netherlands 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. [2022]

7. England 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. [2018]

8. United States 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. [2022]

9. China 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). [2023]

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

Pemetrexed in advanced NSCLC: a review of the clinical data. [2015]

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

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]

12. United States 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. [2023]