Anti-PD-1 + Aldesleukin for Melanoma and Kidney Cancer

Overseen By Stephanie L Goff, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Investigational agents

Disqualifiers: Nursing, Infections, 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: 5

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two drugs, pembrolizumab (an anti-PD-1 therapy) and aldesleukin (also known as interleukin-2 or IL-2), can more effectively treat advanced melanoma and kidney cancer. Both drugs are already used separately for these cancers, and researchers hope the combination will enhance their effectiveness. Adults with these cancer types who have previously tried other treatments may be suitable for this study. Participants will receive the drugs through an IV for a few days, followed by monitoring to track their progress.

As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot be on systemic steroid therapy or other investigational agents. More than four weeks must have passed since your last systemic therapy before enrolling.

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

Research shows that the combination of pembrolizumab and aldesleukin is generally well-tolerated. Pembrolizumab, already used to treat melanoma, has a well-known safety record, having been studied in many patients. Aldesleukin treats advanced melanoma and kidney cancer. It can cause side effects, especially when used alone or in high doses, but these are often manageable.

In studies where both drugs were used together, patients experienced side effects similar to those seen with each drug individually. Most side effects were mild to moderate, such as tiredness, fever, or nausea. Serious side effects were less common.

Overall, the combination of pembrolizumab and aldesleukin appears safe. However, as with any treatment, discussing potential risks and benefits with a doctor is important, considering individual health situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of aldesleukin and pembrolizumab for melanoma and kidney cancer because it offers a novel approach by combining two powerful mechanisms. Pembrolizumab is an anti-PD-1 therapy that helps the immune system detect and attack cancer cells, while aldesleukin is a form of interleukin-2 that boosts the immune response further. This dual-action strategy could enhance the body's ability to fight cancer more effectively than current options, which typically involve either single-agent immunotherapies or targeted therapies. Additionally, the treatment's potential to work in a shorter time frame and possibly improve outcomes makes it a promising candidate in the fight against these cancers.

What evidence suggests that the combination of pembrolizumab and aldesleukin could be an effective treatment for melanoma and kidney cancer?

This trial will evaluate the combination of pembrolizumab and aldesleukin for treating advanced melanoma and kidney cancer. Research has shown that using pembrolizumab and aldesleukin together may benefit people with these conditions. Studies have found that high doses of aldesleukin can lead to long-lasting complete recovery in about 10% of patients with advanced melanoma. Pembrolizumab, a drug that helps the immune system fight cancer, has already proven effective in treating melanoma. Early results suggest that using these two drugs together is safe and might work better than using them alone. This combination aims to boost the body's immune system to fight these cancers more effectively. ^{1 2 3 5 6}

Who Is on the Research Team?

Stephanie L Goff, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with advanced melanoma or renal cell carcinoma can join this trial. They must not have HIV, hepatitis B/C, be pregnant, or breastfeeding. Participants need to have finished any previous cancer treatments at least four weeks prior and agree to use birth control. They should be in good health otherwise, without severe infections or immune system problems.

Inclusion Criteria

I have melanoma or kidney cancer that can be measured for changes.

Subject must be co-enrolled on protocol 03-C-0277

You do not have hepatitis B or hepatitis C in your blood.

Exclusion Criteria

You have a condition that weakens your immune system from birth.

I am currently on steroid medication.

You had a serious allergic reaction to pembrolizumab or aldesleukin in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment - Course 1

Participants receive pembrolizumab and aldesleukin for 2 cycles, each lasting 21 days. Pembrolizumab is administered on Day 1, followed by aldesleukin for up to 4 days.

6 weeks

Inpatient stay for each cycle

Treatment - Course 2

Participants receive pembrolizumab alone for 2 cycles, each lasting 21 days.

6 weeks

Outpatient visits on Day 1 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up visits occur every 3 months for the first year, then every 6 months for up to 5 years.

5 years

Every 3 months x 3, then every 6 months x 8

What Are the Treatments Tested in This Trial?

Interventions

• Aldesleukin
• Pembrolizumab

Trial Overview The trial is testing the combination of two drugs: Aldesleukin and Pembrolizumab given through IV for metastatic melanoma and renal cell carcinoma. The treatment involves hospital stays during cycles and follow-ups for up to five years including physical exams, scans, blood tests.

How Is the Trial Designed?

Group I: 1 - Pembro and IL-2 Experimental Treatment 2 Interventions

Course 1: pembrolizumab (200 mg IV) on Day 1 of each cycle with aldesleukin (600,000 IU/kg intravenous bolus every eight hours) continuing for up to 4 days (maximum 10 doses) for 2 cycles (each 21 days). Course 2: pembrolizumab (200 mg IV) on Day 1 of each cycle for 2 cycles (each 21 days).

Aldesleukin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Proleukin for:

• Metastatic renal cell carcinoma
• Metastatic melanoma

Approved in European Union as Proleukin for:

• Metastatic renal cell carcinoma

Approved in Canada as Proleukin for:

• Metastatic renal cell carcinoma
• 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

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 (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]

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]

Interleukin-2 (IL-2) immunotherapy remains a key treatment for advanced kidney cancer and melanoma, providing substantial and durable benefits for a select group of healthy patients, sometimes leading to cures without ongoing therapy.

Recent advancements in understanding cancer biology and immune mechanisms have led to new targeted and immune-modulatory therapies, which, while beneficial for many patients, typically do not achieve the same long-lasting responses as high-dose IL-2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose interleukin-2: is it still indicated for melanoma and RCC in an era of targeted therapies? Amin, A., White, RL.[2017]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

EMD 273063, an immunocytokine treatment for metastatic melanoma, was found to induce immune activation and was administered safely at a maximum-tolerated dose (MTD) of 7.5 mg/m2/d, with 19 out of 33 patients showing stable disease after the first treatment course.

While there were some grade 3 adverse events, such as hypophosphatemia and hyperglycemia, these were manageable and resolved, indicating that the treatment has a tolerable safety profile despite the associated toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. King, DM., Albertini, MR., Schalch, H., et al.[2021]

A patient with metastatic renal cell carcinoma showed no tumor regression with PD-1 blockade but achieved a near-complete response after receiving high-dose IL-2 therapy, highlighting IL-2's potential as an effective second-line treatment.

This case underscores the importance of developing better predictors for response to immunotherapies, which could help optimize treatment sequences and determine when to switch to alternative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression of metastatic clear cell kidney cancer with interleukin-2 treatment following nivolumab (anti-PD-1) treatment. Brayer, J., Fishman, M.[2020]

Aldesleukin (recombinant IL-2) has shown modest efficacy in treating metastatic melanoma, with response rates up to 56% in combination therapies, but median survival times remain around 10 to 11 months, indicating limited long-term benefits.

The administration methods of aldesleukin have evolved to reduce toxicity, with continuous intravenous infusion and subcutaneous options leading to fewer severe adverse events, but further studies are needed to fully understand its risk/benefit profile compared to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldesleukin (recombinant interleukin-2). Noble, S., Goa, KL.[2022]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9949373/

A phase Ib study of interleukin-2 plus pembrolizumab for ... The objectives of this study were to characterize the safety profile of IL-2 in combination with pembrolizumab in patients with unresectable or metastatic ...

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/PMC4918260/

Update on use of aldesleukin for treatment of high-risk ... High-dose interleukin-2 has been used for the treatment of metastatic melanoma since 1998 based on data proving durable complete responses in up to 10% of ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/show/NCT03111901

Low-dose Interleukin-2 and Pembrolizumab in Melanoma ... This study will evaluate the safety and disease control rate of the combination of pembrolizumab plus low-dose interleukin-2 in patients who have either ...