Nivolumab + Relatlimab + Ipilimumab for Renal Cell Carcinoma

Recruiting at 2 trial locations

Overseen By Eric Jonasch, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: CNS metastases, Autoimmune disease, Myocarditis, 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: 3

Duration: 12 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for advanced kidney cancer. Researchers compare two drug combinations to determine which more effectively stops or slows the cancer. One group will receive three drugs: Nivolumab (Opdivo), Relatlimab (Opdualag), and Ipilimumab (Yervoy), while the other group will receive two. The trial seeks participants with advanced kidney cancer that has spread and who have not received previous systemic treatment for this cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like corticosteroids above a specific dose or other immunosuppressive medications within 14 days before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using nivolumab and ipilimumab together in patients with advanced kidney cancer is generally safe. However, 59% of these patients experienced serious side effects, most commonly related to the immune system. Despite this, many patients lived longer compared to those receiving other treatments.

For the newer combination of nivolumab, relatlimab, and ipilimumab, early results suggest it effectively targets tumors with manageable side effects. This indicates that the side effects are tolerable, and the treatment shows promise in fighting cancer. Overall, while some patients may experience serious side effects, these combinations have been used effectively in similar conditions, providing context for their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for renal cell carcinoma, which often include surgery and targeted therapies like tyrosine kinase inhibitors, the combination of Nivolumab, Relatlimab, and Ipilimumab offers a novel approach. Researchers are excited because this treatment harnesses the power of the immune system by combining immune checkpoint inhibitors. Nivolumab and Ipilimumab block proteins that prevent immune cells from attacking cancer effectively, while Relatlimab targets a different checkpoint protein, potentially enhancing the immune response even further. This multi-faceted attack could lead to a more robust and sustained fight against cancer cells, providing hope for better outcomes.

What evidence suggests that this trial's treatments could be effective for renal cell carcinoma?

Studies have shown that using nivolumab and ipilimumab together can significantly reduce the risk of death for patients with advanced kidney cancer, known as renal cell carcinoma (RCC). Specifically, patients experienced a 28% lower risk of death compared to traditional treatments. This combination is known to improve long-term outcomes. In this trial, one group of participants will receive nivolumab and ipilimumab, while another group will receive nivolumab, ipilimumab, and relatlimab. Research suggests that adding relatlimab to nivolumab and ipilimumab is as effective as the two-drug combination, indicating that the three-drug treatment could be a viable option for treating advanced RCC. ^{1 2 6 7 8}

Who Is on the Research Team?

Eric Jonasch, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer (Renal Cell Carcinoma) who haven't had treatment before. Participants should be fit enough for the treatments and not have any health conditions that could interfere with the study or their safety.

Inclusion Criteria

Women must not be breastfeeding while taking the study drug and for up to five months after the last dose of study drug

Willing and able to provide a signed and dated written informed consent

My kidney cancer includes clear cells.

Exclusion Criteria

Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the investigator to unacceptably increase the risk of study participation

I have or had cancer spread to my brain or spinal cord.

I haven't taken steroids or immunosuppressants in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Nivolumab + Ipilimumab or Nivolumab + Relatlimab + Ipilimumab on an outpatient basis

12 months

Every 3-4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Relatlimab

Trial Overview The study compares two approaches: one group receives a combination of Nivolumab, Relatlimab, and Ipilimumab (triplet), while another gets just Nivolumab and Ipilimumab (doublet). The drugs are given intravenously on different schedules to see which works better against kidney cancer.

How Is the Trial Designed?

Group I: Treatment with Nivolumab + Relatlimab + Ipilimumab Experimental Treatment 2 Interventions

Participants will randonmized to study and treatment will be administered on an outpatient basis.

Group II: Treatment with Nivolumab + Ipilimumab Experimental Treatment 2 Interventions

Participants will randonmized to study and treatment will be administered on an outpatient basis.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Bristol-Myers Squibb

Industry 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

In a study of 129 advanced renal cell carcinoma patients treated with nivolumab and ipilimumab, the occurrence of immune-related adverse events (irAEs) was linked to improved overall survival (OS) and progression-free survival (PFS), with significant hazard ratios indicating a strong positive association.

Patients who experienced multiple irAEs had even better survival outcomes, suggesting that the presence of these adverse events may be a marker for a more favorable response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-related adverse events and survival in patients with renal cell carcinoma treated with nivolumab plus ipilimumab: immortal time bias-corrected analysis. Washino, S., Shirotake, S., Takeshita, H., et al.[2023]

The PRISM study is investigating whether administering ipilimumab every 12 weeks instead of every 3 weeks, when combined with nivolumab, can reduce severe side effects in patients with metastatic renal cell carcinoma (mRCC) without affecting treatment effectiveness.

This phase II trial aims to recruit 189 participants and will primarily measure the rate of grade 3 or 4 adverse reactions over 12 months, while also assessing progression-free survival and other important health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma. Buckley, HL., Collinson, FJ., Ainsworth, G., et al.[2022]

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, when combined with ipilimumab, significantly improves overall survival rates in previously untreated advanced renal cell carcinoma (RCC), achieving an 18-month survival rate of 75% compared to 60% with sunitinib alone.

The combination therapy also results in a higher objective response rate of 42% versus 27% for sunitinib, indicating that immune checkpoint inhibitors are becoming a promising first-line treatment option for metastatic RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline immunotherapy treatment with nivolumab and ipilimumab in metastatic renal cell cancer: a new standard of care. Nizam, A., Aragon-Ching, JB.[2020]

In a real-world analysis of adverse events from two combination therapies for advanced renal cell carcinoma, cabozantinib (CAB) plus nivolumab (NIVO) showed higher incidence rates of seven types of toxicities compared to ipilimumab (IPI) plus NIVO.

Conversely, IPI + NIVO was associated with higher rates of three types of toxicities and had a greater incidence of serious adverse events, suggesting that both therapies have distinct safety profiles that can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. Blas, L., Shiota, M., Tsukahara, S., et al.[2023]

In a study of 45 Japanese patients with untreated metastatic renal cell carcinoma, the combination therapy of nivolumab and ipilimumab showed a 41.5% objective response rate and a median progression-free survival of 17.8 months over a 2-year follow-up period.

The 2-year analysis indicated that nivolumab plus ipilimumab therapy's effectiveness aligns with previous studies, and second-line therapy following this combination also demonstrated a 20% objective response rate with a median progression-free survival of 9.8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of nivolumab plus ipilimumab and second-line therapy in Japanese untreated patients with metastatic renal cell carcinoma: 2-year analysis from a multicenter retrospective clinical study (J-cardinal study). Kojima, T., Kato, R., Sazuka, T., et al.[2022]

In a study of 18 patients with non-clear cell renal cell carcinoma (nccRCC) treated with ipilimumab plus nivolumab, 33.3% achieved partial responses, indicating that this combination therapy can be effective for this type of cancer.

However, the treatment was associated with significant toxicity, with 61.1% of patients experiencing treatment-related adverse events, including serious conditions like colitis and hepatotoxicity, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity of Ipilimumab Plus Nivolumab in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma. Gupta, R., Ornstein, MC., Li, H., et al.[2021]

Nivolumab (Opdivo®) has been established as an effective second-line treatment for metastatic renal cell carcinoma (mRCC), showing improved overall survival (26 months vs. 19.7 months) and response rates compared to Everolimus, based on the CheckMate 025 trial with 1,080 participants.

The combination of Nivolumab and Ipilimumab has demonstrated a significantly higher objective response rate (42% vs. 27%) and better overall survival in intermediate and high-risk patients compared to Sunitinib, while also improving quality of life, despite an increase in immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for renal cell carcinoma - current status]. Grimm, MO., Foller, S.[2019]

Nivolumab combined with ipilimumab significantly improves overall survival in adult patients with intermediate/poor-risk advanced renal cell carcinoma compared to sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

In the study involving 1096 patients, the median overall survival was not reached for the nivolumab + ipilimumab group, while it was 25.95 months for the sunitinib group, highlighting the potential of this combination therapy for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. Ali, S., Camarero, J., Hennik, P., et al.[2021]

In a phase 3 trial involving 1096 patients with untreated advanced renal-cell carcinoma, nivolumab plus ipilimumab significantly improved overall survival rates (75% at 18 months) compared to sunitinib (60% at 18 months), indicating a more effective treatment option for patients with intermediate or poor prognostic risk.

The objective response rate was also higher with nivolumab plus ipilimumab (42%) compared to sunitinib (27%), although both treatments had a high incidence of treatment-related adverse events, with nivolumab plus ipilimumab showing a slightly lower rate of severe (grade 3 or 4) events (46% vs. 63%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. Motzer, RJ., Tannir, NM., McDermott, DF., et al.[2022]

Citations

1. news.bms.com news.bms.com/news/details/2024/Eight-Year-Data-for-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Continue-to-Demonstrate-Longest-Survival-Benefit-vs.-Sunitinib-Reported-in-Patients-with-Previously-Untreated-Advanced-or-Metastatic-Renal-Cell-Carcinoma/default.aspx

Eight-Year Data for Opdivo (nivolumab) Plus Yervoy ... Patients with previously untreated advanced or metastatic renal cell carcinoma treated with Opdivo plus Yervoy experienced a 28% reduction in the risk of death ...

2. opdivo.com opdivo.com/advanced-kidney-cancer/clinical-trial-results/immunotherapy-combination

Clinical trial results for advanced kidney cancer (renal cell ... In the clinical trial, people given OPDIVO + YERVOY had a 37% lower risk of dying than those given SUTENT, and more than half of the people given OPDIVO + ...

3. cancernetwork.com cancernetwork.com/view/nivolumab-combo-may-show-long-term-benefits-in-advanced-rcc

Nivolumab Combo May Show Long-Term Benefits in ... Combining nivolumab (Opdivo) with ipilimumab (Yervoy) may potentially improve long-term outcomes in patients with advanced renal cell carcinoma (RCC).

4. opdivohcp.com opdivohcp.com/efficacy/rcc

Efficacy Data for Renal Cell Carcinoma (RCC) - Opdivo In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%) ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6289271/

Ipilimumab in combination with nivolumab for the treatment of ... The combination of nivolumab and ipilimumab has demonstrated superior efficacy for treatment-naïve patients with intermediate- and poor-risk mRCC with clear ...

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-plus-ipilimumab-combination-intermediate-or-poor-risk-advanced-renal-cell

FDA approves nivolumab plus ipilimumab combination for ... The recommended schedule and dose for this combination is nivolumab, 3 mg/kg, followed by ipilimumab, 1 mg/kg, on the same day every 3 weeks for ...

7. opdivohcp.com opdivohcp.com/safety/rcc

Safety Profile for Renal Cell Carcinoma (RCC) - Opdivo In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions ...

8. aacr.org aacr.org/patients-caregivers/progress-against-cancer/combining-immunotherapy-kidney-cancer-ipilimumab-yervoy-nivolumab-opdivo/

Combining Immunotherapy for Kidney Cancer | The AACR In short, patients who received the combination had significantly improved overall survival rates compared with those who received sunitinib. After a median ...