IL-2 + Pembrolizumab for Kidney Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, 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

Compensation: Varies

Number of Visits: 3

Duration: 9 weeks per block

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for people with metastatic kidney cancer. Researchers use interleukin-2 (IL-2) and pembrolizumab to evaluate their combined effectiveness against this cancer type. IL-2 boosts the immune system, while pembrolizumab helps it recognize and attack cancer cells. This trial may suit those diagnosed with metastatic kidney cancer with clear cell histology who have not received certain prior treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of interleukin-2 (IL-2) and pembrolizumab has been tested in patients with kidney cancer. In past studies, patients responded differently to these treatments. Pembrolizumab, also known as Keytruda™, is already approved for other types of cancer, indicating its safety is well understood. IL-2, or aldesleukin, has been FDA-approved since 1992 for certain kidney cancers and can help some patients.

In one study, patients who received both IL-2 and pembrolizumab experienced side effects such as tiredness, nausea, and fever. These side effects are common with these treatments but were generally manageable with medical help.

Overall, research has previously examined this combination, showing it is somewhat tolerable, though side effects are expected. Participants should discuss potential risks and benefits with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for kidney cancer?

Researchers are excited about combining Interleukin-2 with Pembrolizumab for kidney cancer because it offers a fresh approach compared to standard treatments like surgery, targeted therapies, or traditional immunotherapies. Pembrolizumab is a type of immunotherapy that helps the immune system recognize and attack cancer cells more effectively. When paired with Interleukin-2, which boosts the immune system's response, this combination could enhance the body's ability to fight kidney cancer more powerfully than current options alone. This novel pairing may lead to improved outcomes for patients by harnessing a dual approach to stimulate the immune system against cancer cells.

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

This trial will evaluate the combination of interleukin-2 (IL-2) and pembrolizumab for treating kidney cancer. Research has shown that high doses of IL-2 can shrink or eliminate tumors in about 14% of cases. Pembrolizumab, a treatment that aids the immune system in fighting cancer, has improved outcomes for many cancers, including kidney cancer. In this trial, using these treatments together might enhance the body's ability to attack cancer cells more effectively. Early results suggest that this combination is safe and could be effective, offering hope for better survival rates in patients with advanced kidney cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Jon Chatzkel, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

Adults over 18 with metastatic kidney cancer, specifically clear cell renal carcinoma, who can provide consent and have measurable disease. They must be in good physical condition (ECOG 0 or 1), have proper organ function, agree to use contraception, and not be pregnant. Excluded are those with certain heart conditions, active infections requiring systemic therapy, known psychiatric or substance abuse disorders that could affect participation, recent use of investigational drugs or therapies including anti-PD-1/L1/L2 agents or monoclonal antibodies.

Inclusion Criteria

I agree to use birth control during and for 4 months after the study.

You have a solid tumor that can be measured using specific criteria.

I am willing to provide a tissue sample for the study.

Exclusion Criteria

I haven't had a heart attack, stroke, or major heart surgery in the last year.

I have another cancer besides the one being studied, but it's not getting worse or needing treatment, except for certain skin cancers or cervical cancer that's been treated.

I have a history of or currently have non-infectious lung inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab on weeks 1, 4, and 7, with interleukin-2 added in the second and third blocks for 5 doses at a time

9 weeks per block

3 visits for pembrolizumab, multiple visits for interleukin-2

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Interleukin-2
• Pembrolizumab

Trial Overview The trial is testing the combination of Interleukin-2 (Proleukin™) and Pembrolizumab (Keytruda™) for treating metastatic kidney cancer. The study aims to evaluate the effects when these two treatments are used together.

How Is the Trial Designed?

Group I: Pembrolizumab and Interleukin-2 Experimental Treatment 2 Interventions

Outpatient Intravenous (IV) infusion of Pembrolizumab and Inpatient IV infusion of Interleukin-2.

Interleukin-2 is already approved in United States, European Union for the following indications:

Approved in United States as Aldesleukin for:

• Metastatic melanoma
• Metastatic renal cell carcinoma

Approved in European Union as PROLEUKIN for:

• Metastatic renal cell carcinoma

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Prometheus Laboratories

Industry Sponsor

Trials

27

Recruited

4,800+

Published Research Related to This Trial

Aldesleukin (recombinant interleukin-2) has shown efficacy in treating renal cell carcinoma, with response rates of 13-20% for intravenous and 18-31% for subcutaneous administration, which are higher than the approximately 10% response rates of other treatments.

While aldesleukin can lead to serious side effects, particularly with bolus intravenous administration, the severity of these adverse events is reduced with continuous infusion or subcutaneous administration, making it a potentially safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldesleukin (recombinant interleukin-2): a review of its pharmacological properties, clinical efficacy and tolerability in patients with renal cell carcinoma. Jeal, W., Goa, KL.[2018]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

In a study of 425 patients with metastatic renal-cell carcinoma, the combination of interleukin-2 and interferon alfa-2a resulted in the highest response rate of 18.6%, compared to 6.5% for interleukin-2 alone and 7.5% for interferon alfa-2a alone.

While the combination treatment showed better event-free survival rates (20% at one year), it also had higher toxicity, particularly with interleukin-2, highlighting the need to weigh treatment benefits against potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Français d'Immunothérapie. Negrier, S., Escudier, B., Lasset, C., et al.[2020]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a Phase Ib study involving 10 patients with unresectable or metastatic melanoma, the combination of high-dose interleukin-2 (HD IL-2) and pembrolizumab was found to be feasible and tolerable, with no dose-limiting toxicities observed.

Among the 9 evaluable patients, there was one partial response, indicating some efficacy of the combination treatment, particularly in a patient who had previously received anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib study of interleukin-2 plus pembrolizumab for patients with advanced melanoma. Silk, AW., Curti, B., Bryan, J., et al.[2023]

In a prospective trial involving 120 patients with metastatic renal cell carcinoma (mRCC), high-dose aldesleukin (HD IL2) achieved a 25% objective response rate (ORR), which is significantly higher than historical rates, indicating its efficacy in treating this condition.

The study found that tumor PD-L1 expression was positively associated with response to HD IL2, suggesting it could be a useful biomarker for predicting treatment outcomes, although the integrated selection model (ISM) did not enhance patient selection for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The high-dose aldesleukin "select" trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. McDermott, DF., Cheng, SC., Signoretti, S., et al.[2018]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02964078

Interleukin-2 and Pembrolizumab for Metastatic Kidney ... The main purpose of this study is to evaluate the effects of the interleukin-2 given in combination with pembrolizumab.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.554

Updated efficacy, safety, and correlative analysis of a ... In this abstract, we similarly present extended 6 year follow up results of efficacy, safety, and correlative data from the phase 2 clinical ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1558767322000234

Coordinated Pembrolizumab and High Dose IL-2 (5-in-a- ... This study addressed the safety and feasibility of the combination of IL-2 and pembrolizumab in the treatment of metastatic ccRCC.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4315731/

The High-Dose Aldesleukin “Select” Trial - PubMed Central High-dose aldesleukin (HD IL-2) received FDA approval for the treatment of mRCC in 1992, producing a 14% objective response rate (ORR) and durable ...

5. cancerresearch.org cancerresearch.org/immunotherapy-by-cancer-type/kidney-cancer

Kidney Cancer - Cancer Research ... Immunotherapy for kidney cancer—also called renal cell cancer—has tremendously changed the treatment landscape and overall survival of patients with metastatic ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03260504?term=ALDESLEUKIN&draw=2&rank=2

Aldesleukin and Pembrolizumab in Treating Patients With ... This phase I trial studies the side effects and best dose of aldesleukin when given together with pembrolizumab in treating patients with kidney cancer that ...