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

Launched by NATIONAL CANCER INSTITUTE (NCI) · Dec 10, 2021

Keywords

ClinConnect Summary

This clinical trial is studying the combination of two treatments, pembrolizumab and aldesleukin, to see if they can work better together for patients with advanced skin cancer (melanoma) and kidney cancer (renal cell carcinoma) that has spread to other parts of the body. Pembrolizumab helps the immune system fight cancer, while aldesleukin is designed to boost immune responses. The goal is to find out if using these two drugs together can improve outcomes for patients who have not responded well to other treatments.

To participate in this trial, you need to be an adult aged 18 or older with a confirmed diagnosis of advanced melanoma or renal cell carcinoma that is not responding to previous treatments. You'll undergo several tests to ensure you are a good candidate for the trial, and if eligible, you'll receive the study drugs through an IV in the hospital for a short period. After the initial treatment, you'll have follow-up visits to monitor your health and response to the treatment over the next few years. It's important to note that participation could last up to five years, and you'll need to provide informed consent before starting.

Gender

ALL

Eligibility criteria

• * 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.