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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if a combination of two drugs, nivolumab and relatlimab, can help control a type of kidney cancer called renal medullary carcinoma that has spread or is hard to treat. These drugs work by helping the immune system recognize and attack cancer cells. The goal is to improve treatment outcomes. Nivolumab has been approved for the treatment of various cancers, including renal cell carcinoma, and is often used in combination therapies.

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.

What data supports the effectiveness of the drug Nivolumab for treating renal medullary carcinoma?

Research shows that Nivolumab, a drug that helps the immune system fight cancer, improved survival in patients with a type of kidney cancer called metastatic renal cell carcinoma. This suggests it might also be helpful for other kidney cancers, like renal medullary carcinoma. ^{1 2 3 4 5}

What safety data exists for immunotherapy treatments like Nivolumab and Relatlimab in humans?

Nivolumab, an immunotherapy treatment, has been used in patients with advanced kidney cancer and has shown some immune-related side effects like joint pain, muscle inflammation, and lung issues. However, many patients have experienced long-term benefits even after stopping treatment due to these side effects. ^{3 6 7 8 9}

How is the drug Nivolumab, Relatlimab unique for treating Renal Medullary Carcinoma?

Nivolumab and Relatlimab are unique because they are immune checkpoint inhibitors that help the immune system recognize and attack cancer cells, which is different from traditional treatments that target blood vessel growth or cancer cell growth pathways. This approach is particularly novel for Renal Medullary Carcinoma, a rare cancer with limited standard treatment options. ^{2 4 10 11 12}

Research Team

Pavlos Msaouel

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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 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]

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 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]

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]

References

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

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Bempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study. [2022]

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

Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2018]

6. Japan pubmed.ncbi.nlm.nih.gov

Real-world safety and effectiveness of nivolumab for advanced renal cell carcinoma in Japan: a post-marketing surveillance. [2022]

7. United States 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. [2023]

8. Spain pubmed.ncbi.nlm.nih.gov

Safety of nivolumab in metastatic renal cell carcinoma patients: A real-life experience in a Spanish urology setting. [2021]

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

Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab drug holiday in patients treated for metastatic renal cell carcinoma: A real-world, single-centre experience. [2022]

11. England pubmed.ncbi.nlm.nih.gov

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

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

Nivolumab treatment for advanced renal cell carcinoma: Considerations for clinical practice. [2019]