Triple Drug Therapy for Kidney Cancer

Not currently recruiting at 2 trial locations

Overseen By Eric Jonasch, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Active infection, CNS metastasis, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of three drugs—ciforadenant, ipilimumab, and nivolumab—can help manage advanced kidney cancer, specifically renal cell carcinoma. The researchers seek to assess whether these drugs, when used together, can control the spread of this cancer type. Ideal candidates for this trial have clear cell kidney cancer that has metastasized and have not yet received treatment for the advanced stage. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the trial treatment.

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

Research shows that the combination of ciforadenant, ipilimumab, and nivolumab has been studied for safety in treating advanced kidney cancer. Previous trials have tested this treatment on patients with a poor or moderate outlook for this cancer type.

One study focused on the safety of this combination. Most patients handled the treatment well, though some experienced side effects. The most common side effects included tiredness, diarrhea, and skin rashes, which are typical for treatments like ipilimumab and nivolumab, already approved by the FDA for other cancers.

These early findings suggest that while side effects can occur, the treatment is generally well-tolerated by patients. However, discussing potential risks and benefits with a healthcare provider is important before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ciforadenant, Ipilimumab, and Nivolumab for kidney cancer because this triple therapy offers a unique approach to tackling the disease. While current treatments often rely on either targeted therapies or single-agent immunotherapies, this combination targets multiple pathways to potentially enhance the immune system's response against cancer cells. Ciforadenant works by blocking the A2A receptor, which can help prevent cancer from evading the immune system, while Ipilimumab and Nivolumab are immune checkpoint inhibitors that further boost the body's ability to fight cancer. This multi-faceted strategy may lead to more effective control of advanced renal cell carcinoma, offering hope for improved outcomes in patients.

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

Research has shown that using ciforadenant, ipilimumab, and nivolumab together may help treat advanced kidney cancer. In earlier studies, this combination improved patient outcomes in 34% of cases, outperforming other treatments. Specifically, ipilimumab and nivolumab together lowered the risk of death by 37% in people with advanced kidney cancer compared to SUTENT. Ciforadenant blocks a pathway that allows cancer cells to grow, potentially enhancing the effectiveness of the other two drugs. This trial will evaluate the effectiveness of this three-drug combination, suggesting it could be a strong option for managing advanced kidney cancer. ^{2 5 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?

Adults with Stage IV metastatic renal cell carcinoma who have not had prior systemic therapy for advanced RCC. Participants must have adequate organ function, be willing to use contraception, and able to provide consent. Excluded are those with recent major surgery, active autoimmune diseases, or conditions requiring immunosuppressants.

Inclusion Criteria

Women who can have babies must have a negative pregnancy test within 24 hours before starting the treatment.

I have been diagnosed with clear cell renal cell carcinoma.

I have not received any systemic therapy for advanced kidney cancer.

Exclusion Criteria

I haven't had any cancer treatment, including immune or targeted therapies, in the last 6 months.

I cannot take pills by mouth or have a severe gut problem affecting drug absorption.

I haven't had major surgery in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ipilimumab, nivolumab, and ciforadenant to control advanced renal cell carcinoma

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ciforadenant
• Ipilimumab
• Nivolumab

Trial Overview

The trial is testing a combination of three drugs: Ciforadenant (an adenosine A2a receptor antagonist), Ipilimumab, and Nivolumab in patients with advanced renal cell carcinoma to see if this mix can control the disease better than current treatments.

How Is the Trial Designed?

Group I: Ipilimumab, Nivolumab, and Ciforadenant Experimental Treatment 3 Interventions

To help control advanced renal cell carcinoma.

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

The combination of nivolumab and ipilimumab, which targets PD-1 and CTLA-4 pathways, is an approved frontline therapy for metastatic clear-cell renal cell carcinoma (mccRCC).

This case study demonstrates the safe and effective use of this combination therapy in a 53-year-old patient with mccRCC and end-stage renal disease (ESRD) on hemodialysis, highlighting its potential applicability in populations often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe and effective use of nivolumab plus ipilimumab in a patient with metastatic clear-cell renal cell carcinoma with sarcomatoid dedifferentiation and end stage renal disease on hemodialysis. Shaw, LK., Wiele, AJ., Sircar, K., et al.[2022]

In a pilot study involving 27 patients with metastatic renal cell carcinoma, the combination of interferon-alpha, capecitabine, and thalidomide showed notable antitumor activity, with a 20% partial response rate and 24% of patients achieving stable disease for over 6 months.

The treatment was generally well tolerated, although some patients experienced significant side effects like hand-foot syndrome and neuropathy, indicating that while the combination therapy is promising, further research is needed to optimize its use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon-alpha plus capecitabine and thalidomide in patients with metastatic renal cell carcinoma: a pilot study. Amato, RJ., Rawat, A.[2022]

Combined immune checkpoint blockade (ICB) using nivolumab and ipilimumab shows significant efficacy in treating advanced melanoma, but it also leads to a higher frequency and severity of adverse drug reactions (ADRs) compared to single-agent therapies, based on pooled safety data from 1551 patients.

Most immune-related ADRs are reversible with glucocorticoids, but due to the increased risk and rapid onset of these toxicities, clinicians must be well-trained to monitor and manage these side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. Hassel, JC., Heinzerling, L., Aberle, J., et al.[2022]

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]

In a phase II study involving 34 patients with metastatic renal cell carcinoma, a triple drug bio-chemotherapy regimen combining interleukin-2, interferon-alpha, and 5-fluorouracil achieved an overall objective response rate of 38%, with 9% of patients experiencing complete remission and 29% partial remission.

The treatment was well-tolerated, with only minor side effects reported and no treatment-related deaths, indicating that this regimen may provide significant clinical benefits with a favorable safety profile compared to traditional aggressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunochemotherapy for metastatic renal cell carcinoma using a regimen of interleukin-2, interferon-alpha and 5-fluorouracil. Hofmockel, G., Langer, W., Theiss, M., et al.[2013]

The treatment landscape for locally advanced or metastatic kidney tumors has rapidly evolved since 2005, with the introduction of targeted therapies and immune checkpoint inhibitors enhancing treatment options.

Selecting the most effective medication for patients in different treatment lines remains a significant challenge for clinicians, highlighting the need for comprehensive data and clinical trial results to guide therapy choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second and further lines treatment options for locally advanced or metastatic renal cell carcinoma]. Nagyiványi, K., Géczi, L.[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 52 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, the 1-year progression-free survival rate was 55% and the overall survival rate was 75%, indicating promising efficacy of this treatment combination.

The treatment was associated with a 39% objective response rate, and while 69% of patients experienced immune-related adverse events, the incidence of severe events was lower compared to previous studies, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study. Tanaka, T., Hatakeyama, S., Numakura, K., et al.[2021]

In a long-term follow-up of 94 patients with advanced melanoma treated with nivolumab and ipilimumab, the 3-year overall survival rate was 63%, indicating a promising long-term efficacy of this combination therapy.

The treatment was associated with a 42% objective response rate, but also a significant incidence of grade 3 and 4 adverse events (59%), highlighting the need for careful monitoring of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study. Callahan, MK., Kluger, H., Postow, MA., et al.[2021]

A patient on hemodialysis with advanced clear-cell renal cell carcinoma successfully received combined immune checkpoint blockade therapy with nivolumab and ipilimumab, showing no significant immune-related adverse events.

This case supports the safety and efficacy of using nivolumab and ipilimumab in patients on hemodialysis, suggesting that renal function does not significantly impact the treatment's pharmacokinetics or safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. Kobayashi, Y., Arai, H., Honda, M.[2023]

The combination therapy of nivolumab and ipilimumab is effective for treating advanced renal cell carcinoma, as demonstrated in two case studies of patients receiving this treatment.

Both patients experienced severe immune-related adverse events, including fever, skin rash, and hypotension, which were ultimately diagnosed as anaphylaxis due to the contrast agent used in imaging, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two cases of anaphylaxis due to contrast media during administration of nivolumab and ipilimumab in metastatic renal cell carcinoma. Nezu, K., Katayama, H., Kyan, A.[2020]

The 2018 NCCN Guidelines now endorse adjuvant sunitinib as the first therapy for patients with stage II and III clear cell renal cell carcinoma, indicating its potential effectiveness in this setting.

Ipilimumab plus nivolumab has been introduced as a promising frontline treatment for patients with intermediate and poor-risk advanced renal cell carcinoma, along with cabozantinib as a new first-line option for similar risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updates to the Management of Kidney Cancer. Jonasch, E.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10445575/

Phase 1b/2 trial of Ipilimumab, Nivolumab, and ...

A Phase 1b/2 single-arm, multicenter study to assess safety and efficacy of the combination of ipilimumab, nivolumab, and ciforadenant in the frontline ...

2.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT05501054

NCT05501054 | Phase 1b/2 Trial of Ipilimumab, Nivolumab ...

Study Overview. Brief Summary. To learn if the combination of ciforadenant, ipilimumab, and nivolumab can help to control advanced renal cell carcinoma.

3.

guoncologynow.com

guoncologynow.com/post/ciforadenant-with-ipilimumab-nivolumab-the-role-of-a2ar-blockade-in-the-front-line-rcc-setting

Ciforadenant With Ipi/Nivo: Adding A2AR Blockade in ...

New data on long-term outcomes from phase 3 of KEYNOTE-426 included efficacy and prespecified exploratory biomarker analyses. Read More · 15- ...

4.

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 + ...

5.

clin.larvol.com

clin.larvol.com/trial-detail/NCT05501054

Phase 1b/2 Trial of Ipilimumab, Nivolumab, and ...

"The trial enrolled 50 patients (8 in Phase 1b portion, 42 in Phase 2 portion)....The deep response rate was 34%, demonstrating an improvement compared to ...

6.

urotoday.com

urotoday.com/conference-highlights/astro-2025/astro-2025-kidney-cancer/164034-astro-2025-phase-1b-2-trial-of-ipilimumab-nivolumab-and-ciforadenant-in-first-line-advanced-rcc-a-kidney-cancer-research-consortium-study.html

ESMO 2025: Phase 1b/2 Trial of Ipilimumab, Nivolumab ...

ESMO 2025: Phase 1b/2 Trial of Ipilimumab, Nivolumab, and Ciforadenant in First-line Advanced RCC: A Kidney Cancer Research Consortium Study.

7.

biospace.com

biospace.com/press-releases/corvus-pharmaceuticals-announces-presentation-of-interim-data-from-the-phase-1b-2-clinical-trial-of-ciforadenant-for-patients-with-metastatic-renal-cell-cancer-at-the-european-society-for-medical-oncology-esmo-congress-2025

Corvus Pharmaceuticals Announces Presentation of ...

In addition, 82% of patients in the trial had a poor or intermediate prognosis by International Metastatic Renal Cell Carcinoma Database ...

8.

urologytimes.com

urologytimes.com/view/katy-beckermann-md-on-ciforadenant-plus-ipilimumab-and-nivolumab-in-ccrcc

Katy Beckermann, MD, on ciforadenant plus ipilimumab ...

Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of ...