Relatlimab + Nivolumab for Lymphoma

(RELATIVITY-069 Trial)

Recruiting at 139 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

Trial Summary

What is the purpose of this trial?

This trial is testing two drugs, relatlimab and nivolumab, in children and young adults whose lymphoma has come back or didn't respond to other treatments. These drugs help the immune system recognize and attack cancer cells. The study aims to see if this combination is safe and effective. Nivolumab has demonstrated clinical benefits in multiple tumors, including classical Hodgkin lymphoma.

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.

What data supports the effectiveness of the drug combination Relatlimab + Nivolumab for Lymphoma?

Research shows that nivolumab, a part of the drug combination, has been effective in treating relapsed/refractory diffuse large B-cell lymphoma (DLBCL) by blocking a pathway that tumor cells use to hide from the immune system. Additionally, combining immune checkpoint inhibitors like nivolumab with other agents has shown promise in enhancing treatment benefits for lymphoma. ^{1 2 3 4 5}

Is the combination of Relatlimab and Nivolumab safe for humans?

Nivolumab has been studied for safety in patients with certain types of lymphoma, showing that some patients experienced serious side effects, but these were generally consistent with known effects of similar treatments. While specific data on the combination with Relatlimab is not provided, Nivolumab alone has been used safely in clinical settings. ^{2 6 7 8 9}

How is the drug Relatlimab + Nivolumab unique for treating lymphoma?

Relatlimab + Nivolumab is unique because it combines two immune checkpoint inhibitors, with nivolumab targeting PD-1 and relatlimab targeting LAG-3, offering a novel approach to enhance the immune system's ability to fight cancer. This combination is particularly promising for patients with relapsed or refractory lymphoma, where treatment options are limited. ^{2 10 11 12 13}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 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]

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]

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]

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 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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Avelumab in Combination Regimens for Relapsed/Refractory DLBCL: Results from the Phase Ib JAVELIN DLBCL Study. [2022]

2. United States 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. [2019]

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

Upcoming immunotherapeutic combinations for B-cell lymphoma. [2022]

4. Japan 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. [2023]

5. United States 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. [2022]

6. England 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. [2022]

7. Japan 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. [2022]

8. Switzerland 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. [2023]

9. England 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. [2021]

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

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. [2022]

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

Nivolumab Plus Relatlimab: First Approval. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

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

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