IL-2 + Pembrolizumab for Kidney Cancer

Recruiting in Tampa (>99 mi)

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

27 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to evaluate the effects of the interleukin-2 given in combination with pembrolizumab. Interleukin-2 (IL-2) is also called aldesleukin, or Proleukin™. Pembrolizumab is also called Keytruda™, or anti-PD-1 antibody.

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.

What data supports the effectiveness of the drug IL-2 + Pembrolizumab for kidney cancer?

High-dose aldesleukin (a form of IL-2) has been shown to produce a 14% response rate in patients with metastatic renal cell carcinoma, and pembrolizumab has demonstrated clinical activity in various solid tumors, including kidney cancer, by enhancing the immune system's ability to fight cancer cells. ^{1 2 3 4 5}

Is the combination of IL-2 and Pembrolizumab safe for humans?

Pembrolizumab has been shown to be generally safe in nonhuman primate studies, with no significant toxic effects observed. However, it can cause pneumonitis (lung inflammation) in 1%-5% of patients. High-dose IL-2 can lead to serious side effects like low blood pressure and heart, lung, and kidney issues, but these are usually manageable with treatment adjustments. ^{2 3 6 7 8}

How is the drug IL-2 + Pembrolizumab unique for treating kidney cancer?

The combination of IL-2 and Pembrolizumab is unique because it combines the immune-boosting effects of IL-2 with the immune checkpoint blockade of Pembrolizumab, potentially enhancing the body's ability to fight kidney cancer more effectively than either drug alone. ^{1 2 3 8 9}

Research Team

Jad Cuahoud, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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 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, 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]

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]

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]

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]

References

1. United States 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. [2020]

2. United States 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. [2021]

3. United States 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. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

5. China pubmed.ncbi.nlm.nih.gov

[Clinical study on recombinant human interleukin-2 (Proleukin) in the treatment of metastatic renal cell carcinoma]. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A phase Ib study of interleukin-2 plus pembrolizumab for patients with advanced melanoma. [2023]

8. New Zealand 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. [2018]

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

Coordinated Pembrolizumab and High Dose IL-2 (5-in-a-Row Schedule) for Therapy of Metastatic Clear Cell Renal Cancer. [2022]