Immunotherapy + Tacrolimus for Cancer in Kidney Transplant Recipients

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the effectiveness of combining tacrolimus, nivolumab, and ipilimumab in treating kidney transplant recipients with certain cancers that cannot be surgically removed or have spread. Tacrolimus may slow cancer growth by blocking enzymes, while nivolumab and ipilimumab are immunotherapy drugs that help the immune system attack cancer cells. This approach could prove more effective than traditional treatments like chemotherapy or surgery. Suitable candidates include those with a kidney transplant, a functioning kidney, and specific cancers such as melanoma or basal cell carcinoma, where usual treatments are inadequate.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

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

Research is testing the safety of a combination of three drugs—tacrolimus, nivolumab, and ipilimumab—to treat cancer in individuals who have had a kidney transplant. Previous studies have shown that nivolumab and ipilimumab can help the immune system fight cancer. However, there is concern about how these drugs might affect the transplanted kidney in such patients. In some studies, patients experienced transplant issues and other side effects like tiredness and skin rashes.

This treatment is being tested in an early phase I trial, where researchers primarily assess safety and monitor for side effects. This trial marks the first step in understanding safety, so much remains to be learned. Prospective participants should consult their doctor to understand the possible risks and benefits before joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for cancer in kidney transplant recipients, which often involve chemotherapy or targeted therapy, this new approach uses immunotherapy drugs, ipilimumab and nivolumab, in combination with tacrolimus and prednisone. Researchers are excited because ipilimumab and nivolumab work by activating the immune system to attack cancer cells, potentially offering a more precise and less toxic alternative. Additionally, this combination could help manage the unique challenge of treating cancer in transplant patients without compromising the transplanted kidney. The dual action of stimulating the immune system while controlling immune rejection is what makes this treatment particularly promising.

What evidence suggests that this trial's treatments could be effective for cancer in kidney transplant recipients?

This trial tests tacrolimus, nivolumab, and ipilimumab together to treat cancer in kidney transplant patients. Tacrolimus may inhibit tumor growth by blocking certain enzymes essential for cell growth. Nivolumab and ipilimumab boost the body's immune system to combat cancer. However, earlier studies found that all patients experienced cancer progression when using nivolumab with tacrolimus and prednisone, and adding ipilimumab did not completely halt cancer progression. More research is needed to determine if this combination can effectively treat cancer in these patients. ^{2 3 5 6 7}

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

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03816332

NCT03816332 | Tacrolimus, Nivolumab, and Ipilimumab in ... This phase I trial studies how well tacrolimus, nivolumab, and ipilimumab work in treating kidney transplant recipients with cancer that cannot be removed ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.23.01497

Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for ... Among eight evaluable patients, none met the trial's primary end point. All eight patients experienced PD on NIVO + TACRO + PRED; TRAL occurred ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38252910/

Nivolumab + Tacrolimus + Prednisone ± Ipilimumab ... - PubMed All eight patients experienced PD on NIVO + TACRO + PRED; TRAL occurred in one patient. Six patients then received IPI + NIVO + TACRO + PRED.

4. hopkinsmedicine.org hopkinsmedicine.org/news/newsroom/news-releases/2024/02/immunotherapy-combination-may-benefit-patients-with-transplanted-kidneys-and-advanced-skin-cancers

Immunotherapy Combination May Benefit Patients with ... “The immune suppression we chose prevented nivolumab (anti-PD-1) from working at full effectiveness but didn't fully protect the kidney either,” ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522098185

Ipilimumab for the treatment of advanced melanoma in six ... We report the cases of six kidney transplant recipients treated with ipilimumab for MM in five centers (Table 1). The mean time from renal transplantation (RT) ...

6. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A797

695 Phase 2 study of nivolumab and ipilimumab in ... This multicenter study will enroll up to sixteen KTR with unresectable or metastatic melanoma or basal, cutaneous squamous, or Merkel cell carcinomas.

7. frontierspartnerships.org frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2024.13204/full

Immunotherapy for Cancer in Kidney Transplant Patients The authors conclude that dual therapy with tacrolimus and prednisone does not protect against graft rejection and may decrease the antitumor ...