Relatlimab + Nivolumab for Lymphoma

(RELATIVITY-069 Trial)

Recruiting at 123 trial locations

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

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Anti-CTLA-4, LAG-3 agents

Disqualifiers: CNS lymphoma, Autoimmune disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

68 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medicines, relatlimab and nivolumab, both immunotherapies, to determine their safety and effectiveness in treating certain types of lymphoma, including Hodgkin and non-Hodgkin lymphoma, in children and young adults. It targets those whose cancer has not responded to standard treatments. Ideal participants have recurrent or hard-to-treat lymphoma with visible signs of cancer on scans. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new 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. 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?

Previous studies have shown that the combination of relatlimab and nivolumab is safe and generally well-tolerated. No unexpected safety issues or treatment-related deaths occurred. The body's response to these drugs aligned with existing knowledge, revealing no new or surprising side effects.

These findings suggest that the treatment is manageable for patients, offering encouragement to those considering joining a trial. However, as with any medical treatment, individual experiences may vary, and discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for lymphoma?

Researchers are excited about Relatlimab and Nivolumab for treating lymphoma because they offer a novel approach compared to traditional therapies. Unlike standard treatments, which often focus on directly targeting cancer cells, these drugs work by enhancing the body's immune response to fight the cancer. Relatlimab is a new type of immune checkpoint inhibitor that targets the LAG-3 protein, while Nivolumab targets PD-1, both of which help the immune system to better identify and destroy cancer cells. This combination has the potential to provide a more effective and potentially longer-lasting response for patients with lymphoma.

What evidence suggests that relatlimab plus nivolumab might be an effective treatment for lymphoma?

Research has shown that using the drugs relatlimab and nivolumab together may help treat certain cancers. In this trial, participants will receive this combination. Studies have found that it is safe and generally well-tolerated, with no unexpected side effects. When combined with chemotherapy, it benefited patients with advanced non-small cell lung cancer. It also performed as well as other similar treatments for advanced melanoma. These results suggest that using relatlimab and nivolumab together could also be effective for some types of lymphoma. ^{1 2 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 young individuals with high-risk, recurrent or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma who haven't responded to standard therapy. They must have measurable disease confirmed by PET scan and not have had certain prior treatments like anti-CTLA-4 antibodies or stem cell transplants.

Inclusion Criteria

My cancer shows up on PET scans.

My lymphoma has not improved after second-line treatment.

My Hodgkin lymphoma did not respond to the first standard treatment.

Exclusion Criteria

My condition is an aggressive B-cell lymphoma, such as Burkitt lymphoma.

My lymphoma affects my brain, spinal cord, or has spread within its coverings.

I have been treated with drugs targeting LAG-3.

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 to assess safety, tolerability, drug levels, and preliminary efficacy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

19 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Relatlimab

Trial Overview The study tests the combination of Relatlimab plus Nivolumab in pediatric and young adult patients. It aims to determine how safe this combo is, how well it's tolerated, what levels of the drugs stay in the body, and if it effectively treats these types of lymphomas.

How Is the Trial Designed?

Group I: Relatlimab + Nivolumab Experimental Treatment 2 Interventions

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

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

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

Nivolumab plus relatlimab is a combination immunotherapy that targets immune checkpoints, specifically PD-1 and LAG-3, and has been approved for treating unresectable or metastatic melanoma in adults and adolescents weighing at least 40 kg.

This combination therapy represents a significant advancement in cancer treatment, as it utilizes two different mechanisms to enhance the immune response against cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab: First Approval. Paik, J.[2022]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

PD-1 blockade has shown high efficacy in treating relapsed/refractory classical Hodgkin lymphoma, with objective response rates (ORRs) between 65% to 87% and a median duration of response of 16 months in clinical trials.

While PD-1 blockade is effective in certain B-cell lymphomas, such as primary mediastinal large B-cell lymphoma (ORR of 35%), it has limited efficacy in others like chronic lymphocytic leukemia (0% ORR), highlighting the importance of tumor-specific characteristics in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Xu-Monette, ZY., Zhou, J., Young, KH.[2022]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

In a study of 46 patients with high-risk diffuse large B-cell lymphoma (DLBCL), the combination of durvalumab with R-CHOP chemotherapy resulted in a 54.1% complete response rate, indicating that this treatment approach is feasible for these patients.

Despite the promising response rates, the addition of durvalumab did not show greater efficacy compared to R-CHOP alone, and the safety profile was consistent with standard R-CHOP treatment, suggesting no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab with R-CHOP or R2-CHOP in untreated, high-risk DLBCL: a phase 2, open-label trial. Nowakowski, GS., Willenbacher, W., Greil, R., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

In a study of 177 patients with CD20(+) non-Hodgkin's lymphoma, rapid rituximab infusion (RRI) combined with chemotherapy showed promising safety, with most infusion reactions being mild (grade I - II) and only a few severe reactions (grade III - IV).

The treatment demonstrated high efficacy, with a 3-year overall survival rate of 93.1% and a progression-free survival rate of 81.1%, indicating that RRI is a feasible option for enhancing treatment in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of non-initial rapid infusion of rituximab plus chemotherapy in Chinese patients with CD20+ non-Hodgkin's lymphoma. Zhao, W., Gao, Y., Bai, B., et al.[2022]

In a phase II study involving 121 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), nivolumab showed a low overall response rate of 10% in those who failed autologous hematopoietic cell transplantation (auto-HCT) and 3% in those ineligible for auto-HCT, indicating limited efficacy in this patient population.

Despite the low response rates, nivolumab demonstrated a favorable safety profile, with only 24% of patients experiencing grade 3 or 4 adverse events, primarily neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study. Ansell, SM., Minnema, MC., Johnson, P., et al.[2019]

In a phase 1b trial involving 137 patients with relapsed/refractory lymphoid malignancies, the combination of nivolumab with ipilimumab or lirilumab showed significant activity in classical Hodgkin lymphoma, with overall response rates of 74% and 76%, respectively.

However, the combination therapies did not demonstrate a meaningful improvement in efficacy compared to single-agent nivolumab, and the combination with ipilimumab resulted in higher rates of severe treatment-related adverse events (29%) compared to lirilumab (15%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies. Armand, P., Lesokhin, A., Borrello, I., et al.[2021]

Combination therapies for B-cell lymphomas are increasingly incorporating immune checkpoint inhibitors and other immunotherapies, reflecting a significant evolution in treatment strategies for both adults and children.

Future clinical trials are expected to focus on tailored treatments that combine established chemotherapy with new agents, utilizing innovative trial designs to better target specific genetic changes in tumors and enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upcoming immunotherapeutic combinations for B-cell lymphoma. Greve, P., Meyer-Wentrup, FAG., Peperzak, V., et al.[2022]

In a study of 21 patients with relapsed and refractory classic Hodgkin lymphoma who had previously failed nivolumab treatment, the combination of nivolumab and brentuximab vedotin showed a promising overall response rate of 57%.

The treatment was found to be relatively safe, with 63% of patients experiencing any grade adverse events, and only 10% experiencing severe (grade 3-4) adverse events, suggesting that this combination therapy could be a viable option for patients after PD-1 inhibitor failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma. Fedorova, LV., Lepik, KV., Volkov, NP., et al.[2023]

In a phase 1b study involving 32 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the combination of durvalumab with either tremelimumab or danvatirsen was generally well tolerated, with treatment-related adverse events occurring in 65.6% of patients, primarily involving liver enzyme increases and fatigue.

Despite the treatment's tolerability, the overall objective response rate was low at 6.3%, indicating limited antitumor activity, with a median overall survival of 28 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Ribrag, V., Lee, ST., Rizzieri, D., et al.[2022]

In a phase Ib study involving 29 adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the combination of avelumab with other agents showed limited clinical activity, leading to the discontinuation of the study before phase III.

While avelumab was generally safe with no new safety concerns, only one partial response and three complete responses were observed, indicating that PD-L1 inhibitors may have limited effectiveness in treating R/R DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in Combination Regimens for Relapsed/Refractory DLBCL: Results from the Phase Ib JAVELIN DLBCL Study. Hawkes, EA., Phillips, T., Budde, LE., 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. 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.

3. ashpublications.org ashpublications.org/bloodadvances/article/9/13/3383/535818/Nivolumab-plus-relatlimab-for-patients-with

Nivolumab plus relatlimab for patients with relapsed or ... Nivolumab plus relatlimab was overall safe, tolerable, and manageable with no unexpected safety signals or treatment-related deaths. The combination of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10164023/

The Latest Option: Nivolumab and Relatlimab in Advanced ... Based on the results of two phase 2 trials the combination therapy with ipilimumab and nivolumab lead to an ORR of up to 56% intracranially in patients with ...

5. cancernetwork.com cancernetwork.com/view/relatlimab-shows-comparable-efficacy-to-ipilimumab-in-advanced-melanoma

Relatlimab Shows Comparable Efficacy to Ipilimumab in ... The addition of relatlimab (Opdualag) to nivolumab (Opdivo) exhibited comparable efficacy outcomes vs ipilimumab (Yervoy) and nivolumab in patients with ...

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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05255601

NCT05255601 | A Study to Evaluate the Safety, Tolerability ... The purpose of this study is to assess the safety, tolerability, drug levels, and preliminary efficacy of relatlimab plus nivolumab in pediatric and young adult ...

8. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2200239

Overall Survival and Response with Nivolumab and ... The fixed-dose combination of nivolumab + relatlimab showed consistent PFS benefit versus nivolumab with approximately 6 months of additional median follow-up.