Immunotherapy for Renal Medullary Carcinoma

Overseen By Pavlos Msaouel, MD,PHD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticancer therapies, High-dose steroids

Disqualifiers: Other malignancies, Autoimmune disease, HIV, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of two drugs, nivolumab (Opdivo) and relatlimab (Opdualag), can control renal medullary carcinoma (RMC), an advanced or metastatic type of kidney cancer. The goal is to determine if these drugs can slow or stop the cancer's growth. Individuals with RMC confirmed by medical tests, who have experienced tumor growth after previous treatments, and who have not tried certain immune therapies before, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any anticancer therapies or high-dose steroids when starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that the combination of nivolumab and relatlimab is likely to be safe for humans?

Research has shown that using nivolumab and relatlimab together has a manageable safety profile for patients. In past studies with melanoma patients, the side effects matched those expected from these drugs when used separately. This means the side effects were not surprising and resembled those seen with other treatments. Although some sources did not provide detailed safety data, the consistent results across studies offer reassurance about their safety. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for renal medullary carcinoma?

Researchers are excited about the combination of nivolumab and relatlimab for treating renal medullary carcinoma because this approach offers a novel mechanism of action. Unlike the standard treatments, which often involve chemotherapy or targeted therapies, nivolumab and relatlimab work together to enhance the immune system's ability to fight cancer. Nivolumab is an immune checkpoint inhibitor that targets the PD-1 pathway, while relatlimab inhibits the LAG-3 protein, both of which help unleash the body's natural defenses against cancer cells. This dual-action strategy could potentially provide more effective and durable responses compared to existing options.

What evidence suggests that the combination of nivolumab and relatlimab could be effective for renal medullary carcinoma?

Research has shown that the combination of nivolumab and relatlimab, known as Opdualag, yields promising results in cancer treatment. In this trial, participants will receive this combination treatment. Studies indicate that this drug pair can double the time patients live without their cancer worsening compared to standard treatments, particularly in advanced melanoma. Patients with certain cancers responded better to this combination than to nivolumab alone. Although this data pertains to other cancers, it suggests that Opdualag might also be effective for renal medullary carcinoma. The combination enhances the immune system's ability to fight cancer cells more effectively. ^{1 6 7 8 9}

Who Is on the Research Team?

Pavlos Msaouel

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced or metastatic renal medullary carcinoma (RMC), who may or may not have had a kidney removed, and are not currently pregnant or breastfeeding. Participants need to have proper organ function, can be treatment-naïve or previously treated for RMC, and must agree to use effective contraception. Those with controlled brain metastases post-treatment are eligible; however, individuals with severe medical conditions, other recent cancers, HIV/AIDS, uncontrolled brain metastases, active myocarditis or hepatitis B/C infection cannot join.

Inclusion Criteria

Your condition must have gotten worse after your last treatment.

My kidney cancer is advanced or has spread and shows medullary features.

Consent to MD Anderson companion laboratory protocol 2014-0938

Exclusion Criteria

You have tested positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

I have not received any live vaccines within a week of signing up or during the study.

You have a positive COVID-19 test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab 480 mg IV plus relatlimab 480 mg IV every 4 weeks for up to 2 years

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Relatlimab

Trial Overview The trial is testing the effectiveness of combining two immunotherapy drugs—nivolumab and relatlimab—in treating RMC that has spread beyond the kidney. The study aims to see if this drug combination can control the disease's progression in patients who meet specific health criteria.

How Is the Trial Designed?

Group I: Nivolumab+Relatlimab Experimental Treatment 2 Interventions

nivolumab 480 mg IV plus relatlimab 480 mg IV every 4 weeks for up to 2 years

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Lenvatinib plus pembrolizumab had the highest rates of severe treatment-related adverse events (grade ≥3 TRAEs) and treatment discontinuation among the combination therapies for advanced renal cell carcinoma.

Nivolumab plus ipilimumab had the lowest rates of severe TRAEs but was linked to more endocrine-related adverse events, highlighting the need to balance efficacy with safety in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of systemic immune-based combination therapies in the first-line treatment of patients with metastatic renal cell carcinoma: systematic review and network meta-analysis. Quhal, F., Mori, K., Remzi, M., et al.[2023]

In a retrospective study of 26 patients with metastatic renal cell carcinoma treated with nivolumab, all patients experienced some form of adverse event, with fatigue, fever, and anemia being the most common, affecting 27% of patients.

Despite the occurrence of adverse events, including grade 3 reactions in 23% of patients, nivolumab demonstrated favorable safety outcomes in a real-life clinical setting, consistent with findings from other studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of nivolumab in metastatic renal cell carcinoma patients: A real-life experience in a Spanish urology setting. Amores Bermúdez, J., Osman García, I., Unda Urzáiz, M., et al.[2021]

In a study of 91 patients with metastatic renal cell carcinoma (mRCC), nivolumab showed significant improvements in overall survival, with a median survival of 25.2 months for the highest dose (10 mg/kg) and not reached for treatment-naïve patients.

Nivolumab treatment led to substantial increases in tumor-associated lymphocytes and changes in chemokine levels, indicating its immunomodulatory effects, while no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. Choueiri, TK., Fishman, MN., Escudier, B., et al.[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 is a promising immunotherapy for advanced renal cell carcinoma (aRCC) that works differently than traditional therapies targeting blood vessel growth, offering a new treatment option for patients.

The commentary reviews clinical experiences and practical considerations for using nivolumab, highlighting its unique response patterns and safety profiles compared to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab treatment for advanced renal cell carcinoma: Considerations for clinical practice. Joseph, RW., Chatta, G., Vaishampayan, U.[2019]

In a study of 389 metastatic renal cell carcinoma patients with poor prognostic features, nivolumab demonstrated a disease control rate of 53% in those with brain metastasis, 45% in liver metastasis, and 47% in bone metastasis, indicating its efficacy in difficult-to-treat populations.

The safety profile of nivolumab remained consistent with previous studies, with no new safety concerns identified, suggesting it is a safe treatment option for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Negative prognostic factors and resulting clinical outcome in patients with metastatic renal cell carcinoma included in the Italian nivolumab-expanded access program. Bracarda, S., Galli, L., Maruzzo, M., et al.[2018]

Nivolumab, an anti-PD-1 antibody, shows promising effects in the treatment of advanced renal cancer, indicating its potential as an effective immunotherapy option.

The manuscript highlights the role of nivolumab in harnessing the immune system to target and combat renal cancer, suggesting a new avenue for treatment in this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nivolumab (Anti-PD-1 antibody; ONO-4538/BMS-936558) in renal cancer]. Ozono, S.[2018]

In a study of 46 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, 72% experienced immune-related adverse events (irAEs), which were linked to significantly longer progression-free survival (PFS) compared to those without irAEs.

While irAE development was an independent predictor of longer PFS, it did not affect overall survival (OS), suggesting that irAEs could serve as a useful prognostic marker for treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Ikeda, T., Ishihara, H., Nemoto, Y., et al.[2022]

Citations

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Clinical Review - Nivolumab and Relatlimab (Opdualag) - NCBI According to OH-CCO's Skin Cancer DAC, the drug under review has a higher response rate compared with single-drug nivolumab in patients with unresectable or ...

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. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1349081/full

Relatlimab: a novel drug targeting immune checkpoint LAG ... A randomized, open-label phase II clinical trial studying the use of relatlimab and nivolumab in treating advanced hepatocellular carcinoma patients who have ...

4. 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 ...

5. gatewaycr.org gatewaycr.org/for-researchers/clinical-trials/phase-ii-trial-of-relatlimab-plus-nivolumab-in-renal-medullary-carcinoma/

Phase II Trial of Relatlimab plus Nivolumab in Renal ... This phase II study will assess the overall response rate of nivolumab in combination with relatimab in patients with RMC.

6. opdualaghcp.com opdualaghcp.com/

Opdualag® (nivolumab and relatlimab-rmbw) | Healthcare ... Safety Data. Find information about adverse reactions seen in the clinical ... There are no data on the presence of OPDIVO or YERVOY in human milk, the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10806167/

Relatlimab: a novel drug targeting immune checkpoint LAG ... In this trial, the combination therapy of relatlimab and nivolumab also demonstrated manageable safety. The results above indicate that in melanoma patients ...

8. 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 ... The safety profile of Opdualag observed in this analysis was consistent with the known profiles of nivolumab and relatlimab. “We are ...

9. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2024/PC0329-Opdualag_combined.pdf

Nivolumab and Relatlimab (Opdualag) No data were presented on specific safety outcomes of potential interest, nor on overall ... assessed in terms of OS and tolerability of nivolumab-relatlimab FDC ...