Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma

NCT05155033 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10000354000354-C
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

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

Keywords

Immunotherapy; Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• Response rate in treatment refractory disease

  Determine the rate of objective response (using RECIST v1.1 criteria)

  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)

Secondary Outcomes (3)

• Progression Free Survival

  Every 2-6 months for up to 5 years

• Response rate in treatment naive melanoma

  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)

• Safety and tolerance

  First dose through 30 days after last treatment

Study Arms (1)

1 - Pembro and IL-2

EXPERIMENTAL

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).

Drug: Pembrolizumab; Drug: Aldesleukin

Interventions

Pembrolizumab DRUG

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

1 - Pembro and IL-2

Aldesleukin DRUG

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.

1 - Pembro and IL-2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Melanoma; Carcinoma, Renal Cell

Interventions

pembrolizumab; aldesleukin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Stephanie L Goff, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI SB Immunotherapy Recruitment Center

CONTACT

(866) 820-4505; irc@nih.gov

Stephanie L Goff, M.D.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2021
• First Posted: December 13, 2021
• Study Start: August 18, 2022
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2031
• Last Updated: February 17, 2026

Record last verified: 2026-02-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)