Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Status:
Not yet recruiting
Trial end date:
2025-09-01
Target enrollment:
Participant gender:
Summary
Background:
High-dose interleukin-2 was approved by the FDA for the treatment of metastatic melanoma and
renal cell carcinoma, with overall response rates of 15-16%. Complete regression of disease
was seen in 6-7% of participants with many long-term durable responses. The regimen has not
been widely adopted due to complexities in management and the development of alternative
effective therapies, such as monoclonal antibodies targeting immune checkpoints (ipilimumab,
pembrolizumab, nivolumab) or small molecule inhibitors.
Pembrolizumab was approved by the FDA for the treatment of metastatic melanoma based on a
series of studies demonstrating objective response rates from 21-34%. There remains a
considerable population of participants with disease that never responded to treatment, in
addition to participants with short durations of response prior to recurrence.
There has been limited clinical investigation of the combination of interleukin-2 and
pembrolizumab. The hypothesis under investigation is that non-specific activation of the
immune system with both positive stimulation (aldesleukin) and release of negative regulation
(pembrolizumab) may have meaningful clinical impact for participants with limited therapeutic
options.
Objectives:
Primary:
To determine the objective response rate as determined by RECIST 1.1 criteria to combined
aldesleukin and pembrolizumab in participants with advanced melanoma refractory to anti-PD-1
therapy and treatment-refractory metastatic renal cell carcinoma
Secondary:
To determine progression free survival with the combined regimen
To determine the toxicity profile of this treatment regimen
To determine the objective response rate as determined by RECIST 1.1 criteria to combined
aldesleukin and pembrolizumab in participants with treatment-na(SqrRoot) ve advanced melanoma
Exploratory:
To evaluate clinical and laboratory correlates of response
To perform immunologic correlative studies of peripheral blood, tumor, and/or tumor
infiltrating lymphocytes including but not limited to phenotype and functional analysis of
longitudinal samples
Eligibility:
Participants must be/have:
Age >= 18 years of age.
ECOG performance status of 0 or 1.
Expected survival of greater than 6 months.
Histologically or cytologically confirmed melanoma or renal cell cancer, as follows:
Cohort 1: Metastatic melanoma or advanced locoregional melanoma not amenable to curative
surgical resection and refractory to anti-PD-1 therapy.
Cohort 2: Metastatic renal cell carcinoma (clear cell histology) refractory to at least one
line of PD1/PDL1 based therapy.
Cohort 3: Metastatic or advanced locoregional melanoma not amenable to curative surgical
resection na(SqrRoot) ve to anti-PD-1 therapy.
No allergies or hypersensitivity to high-dose aldesleukin or pembrolizumab administration.
No concurrent major medical illnesses or any form of immunodeficiency.
No history of Grade 3/4 immune-related adverse events affecting major organ systems
associated with the administration of single agent pembrolizumab or nivolumab.
Design:
Study treatment will be given in two courses. A course shall consist of two cycles (each 21
days) of treatment. Cycles in Course 1 shall consist of pembrolizumab (200 mg IV) infusion on
the morning of Day 1 with aldesleukin (IL-2) administration (600,000 IU/kg intravenous bolus
every eight hours) to begin later that day. IL-2 will be administered to tolerance or to a
maximum of 10 doses.
A second cycle of treatment will begin on Day 21 (+ 7 days).
Approximately two months from the beginning of therapy, participants will be evaluated for
response including physical exam, clinical laboratory testing, and cross-sectional imaging.
Participants that do not demonstrate progressive disease will receive a second course of
pembrolizumab alone, if clinically appropriate.
Participants with stable disease will be monitored until disease progression (every 3 months
x 3) up to one year.
Participants with an objective response will be monitored until disease progression (every 3
months x 3, every 6 months x 8) up to five years.