Recruiting
Phase 2

Pembrolizumab & Aldesleukin

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05155033

Conditions

Metastatic Melanoma

Advanced Locoregional Melanoma

Metastatic Renal Cell Carcinoma

Clear Cell Histology

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Pembrolizumab

Aldesleukin

Study Details

Brief summary:

Background:

Aldesleukin is used to treat metastatic or advanced melanoma and renal cell carcinoma. Pembrolizumab is used to treat many cancers including melanoma. Researchers want to see if these drugs can be used together to produce better results in people with these types of cancer.

Objective:

To learn if the combination of pembrolizumab and aldesleukin can be used to treat metastatic or advanced melanoma and renal cell cancer.

Eligibility:

Adults aged 18 years or older who have metastatic or advanced melanoma or renal cell carcinoma.

Design:

Participants will be screened with:

  • Medical history
  • Physical exam
  • Electrocardiogram
  • Blood and urine tests
  • Ability to perform tasks of daily living
  • Imaging scans (CT, MRI, PET, and/or X-rays). They may get a contrast agent to enhance the images.
  • Photographs, if needed

Some of these tests will be repeated during the study.

Participants will receive the study drugs by IV (a plastic tube that is put into a vein) for 4 days. A second cycle of treatment will be given 21 days later. They will stay in the hospital for each of the cycles in the first course of treatment. After 2 months, their cancer will be evaluated. They may receive a second course of pembrolizumab alone on Days 1 and 21. They will not have to stay in the hospital for this course.

About 30 days after treatment ends, participants will have a safety follow-up visit. Then they will have visits every 3 months for up to 1 year, and then every 6 months for up to 4 years. Follow-up can also be done by phone, email, and mail. If their cancer gets worse, they will stop having visits.

Participation will last for 5 years....

Conditions

Metastatic Melanoma

Advanced Locoregional Melanoma

Metastatic Renal Cell Carcinoma

Clear Cell Histology

Study ID

NCT05155033

Start date

Aug 18, 2022

Status verified date

Aug 17, 2026

Completion date

Sep 1, 2031

Anticipated

Primary completion date

Sep 1, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • INCLUSION CRITERIA:
  • Participants must have histologically or cytologically confirmed cancer that falls into one of three cohorts: (1) metastatic melanoma or advanced locoregional melanoma not amenable to curative surgical resection and refractory to anti-PD-1 therapy; (2) metastatic renal cell carcinoma (clear cell histology) refractory to at least one line of PD1/PDL1 based therapy; (3) metastatic or advanced locoregional melanoma not amenable to curative surgical resection and naive to anti-PD-1 therapy.
  • Participants must have measurable disease (per RECIST v1.1 criteria), metastatic melanoma or renal cell cancer.
  • Age >=18 years of age.
  • Clinical performance status of ECOG 0 or 1.
  • Willing to practice birth control from the time of enrollment on this study and for four months after treatment.
  • Must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
  • Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • Seronegative for hepatitis B antigen and for hepatitis C antibody. If hepatitis C antibody test is positive, then participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  • Participants must have adequate organ and marrow function as defined below:

  • ANC > 1000/mm\^3 without the support of filgrastim
  • WBC >= 3000/mm\^3
  • Platelet count >= 100,000/mm\^3
  • Hemoglobin > 8.0 g/d (Subject may be transfused to reach this cut-off)
  • Serum ALT/AST <= 5.0 x ULN
  • Serum creatinine <= 1.6 mg/dL
  • Total bilirubin <= 2.0 mg/dL, except in participants with Gilbert s Syndrome, who must have a total bilirubin < 3.0 mg/dL.
  • More than four weeks must have elapsed since completion of any prior systemic therapy at the time of enrollment.

Note: Participant may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to <= grade 1.

  • Ability of subject to understand and the willingness to sign a written informed consent document.
  • Willing to sign a Durable Power of Attorney Form.
  • Subject must be co-enrolled on protocol 03-C-0277

EXCLUSION CRITERIA:

  • Participant is nursing because of the potentially dangerous effects of the treatment on the fetus or infant.
  • Concurrent systemic steroid therapy.
  • Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
  • History of major organ autoimmune disease.
  • Grade 3 or 4 major organ irAEs following treatment with anti-PD-1/PD-L1 monotherapy, including but not limited to myocarditis, pneumonitis, colitis, and hepatotoxicity.
  • Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • History of severe immediate hypersensitivity reaction to pembrolizumab or aldesleukin.
  • History of coronary revascularization or ischemic symptoms.
  • For select participants with a clinical history prompting cardiac evaluation: last known LVEF <= 45%.
  • For select participants with a clinical history prompting pulmonary evaluation: known FEV1 <= 50%.
  • Participant is receiving any other investigational agents.

Study Design

Enrollment

78 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 1 - Pembro and IL-2

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).

Interventions

Pembrolizumab

Pembrolizumab 200 mg IV over approximately 30 minutes on Day 1 of cycles 1 and 2 during Courses 1 and 2.

Aldesleukin

Aldesleukin (IL-2) administration \[600,000 IU/kg IV bolus every 8 hours continuing for up to 4 days (maximum 10 doses)\] starting on Day 1 of cycles 1 and 2 during Course 1.

Primary outcome measure

  • Response rate in treatment refractory disease [ Time Frame: 8 weeks after Course 1 Cycle 1 then after Course 2, every 3 months x 3 (up to one year), every 6 months x 8 (up to five years) ]

Central Contacts and Locations

Central contacts

NCI SB Immunotherapy Recruitment Center

(866) 820-4505irc@nih.gov

Stephanie L Goff, M.D.

(240) 760-6214stephanie.goff@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

NCI/Surgery Branch Recruitment Center

866-820-4505irc@nih.gov

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 8, 2026

Last verified

Aug 17, 2026

Keywords

  • Immunotherapy
  • Monoclonal Antibody

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-08.