Immunotherapy + Tacrolimus for Cancer in Kidney Transplant Recipients

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Tacrolimus

Must not be taking: Investigational agents

Disqualifiers: Liver transplant, CNS metastases, Autoimmune diseases, 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

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I trial studies how well tacrolimus, nivolumab, and ipilimumab work in treating kidney transplant recipients with cancer that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Tacrolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tacrolimus, nivolumab, and ipilimumab may work better in treating kidney transplant recipients with cancer compared to chemotherapy, surgery, radiation therapy, or targeted therapies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients must not be receiving any other investigational agents and must not have had chemotherapy or radiotherapy within 4 weeks of study entry. It's best to discuss your specific medications with the study team.

Is the combination of immunotherapy drugs like nivolumab and ipilimumab safe for kidney transplant recipients?

The combination of nivolumab and ipilimumab has been used safely in patients with advanced kidney cancer, even those on dialysis, but it can cause immune-related side effects, including kidney injury. In kidney transplant recipients, there is a risk of graft rejection, especially with nivolumab. ^{1 2 3 4 5}

How is the drug combination of Ipilimumab and Nivolumab unique for cancer in kidney transplant recipients?

The combination of Ipilimumab and Nivolumab is unique because it uses immune checkpoint inhibitors to enhance the body's immune response against cancer, but it poses a high risk of kidney transplant rejection, which is a significant concern for transplant recipients. ^{1 6 7 8 9}

What data supports the effectiveness of the drug combination of immunotherapy and tacrolimus for cancer in kidney transplant recipients?

The combination of nivolumab and ipilimumab has shown improved overall survival in patients with advanced renal cell carcinoma, and immune checkpoint inhibitors like these have been effective in treating various cancers. However, their use in kidney transplant patients carries a high risk of organ rejection, indicating a need for careful management. ^{6 7 8 9 10}

Who Is on the Research Team?

Evan Lipson, MD

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for kidney transplant recipients with certain advanced cancers (melanoma, basal cell carcinoma, Merkel cell carcinoma, squamous cell carcinoma) that can't be removed or have spread. Participants must be in fair health based on ECOG status, meet specific blood test criteria, use contraception if applicable, and may include HIV-positive patients under effective treatment.

Inclusion Criteria

I have records showing I've considered or been deemed ineligible for certain cancer treatments.

I have a working kidney transplant and don't need dialysis.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

My cancer has not spread to my brain or spinal cord.

I have no prior evidence of specific immune system antibodies against a transplant.

I do not have any severe illnesses or mental health issues that would stop me from following the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive tacrolimus and prednisone orally, and nivolumab intravenously every 4 weeks for up to 24 cycles (96 weeks) in the absence of disease progression or unacceptable toxicity.

96 weeks

Secondary Treatment

Participants with progressive disease or allograft loss at 16 weeks receive nivolumab and ipilimumab intravenously every 3 weeks for 4 cycles (12 weeks), followed by nivolumab every 4 weeks for up to 21 cycles (84 weeks).

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 8 weeks for year 1, every 12 weeks for year 2, every 16 weeks for year 3, and every 24 weeks for year 4. Patients with progressive disease are followed every 12 weeks for up to 5 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Tacrolimus

Trial Overview The study tests tacrolimus combined with the monoclonal antibodies nivolumab and ipilimumab to see if they're more effective than traditional treatments for cancer in kidney transplant recipients. The goal is to harness the body's immune system to fight cancer while considering the unique circumstances of organ transplant patients.

How Is the Trial Designed?

Group I: Treatment (tacrolimus, prednisone, nivolumab, ipilimumab) Experimental Treatment 4 Interventions

Patients receive tacrolimus PO BID and prednisone PO QD. Within 28 days, patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 24 cycles (96 weeks) in the absence of disease progression or unacceptable toxicity. Patients who experience PD or patients who have experienced allograft loss at 16 weeks receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Patients also receive tacrolimus PO BID and prednisone PO QD. Cycles repeat every 3 weeks for 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Starting 6 weeks later, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 21 cycles (84 weeks) in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

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]

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 35 patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab, 62.9% experienced immune-related adverse events, which were associated with significantly longer progression-free and overall survival rates.

The presence of immune-related adverse events, particularly skin reactions, was identified as an independent predictor of better clinical outcomes, suggesting that these events could serve as effective biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. Ueda, K., Suekane, S., Kurose, H., et al.[2022]

Citations

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

A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword? [2020]

3. England 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. [2021]

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

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

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

Use of Ipilimumab and Pembrolizumab in Metastatic Melanoma in a Combined Heart and Kidney Transplant Recipient: A Case Report. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. [2023]

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

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Development of Nivolumab/Ipilimumab-Associated Autoimmune Nephritis during Steroid Therapy. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. [2022]