low-dose interleukin-2 and pembrolizumab in melanoma and renal cell cancer

Conditions: Carcinoma, Renal Cell; Melanoma

Summary: 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 advanced melanoma or renal cell cancer.


Eligibility criteria:
main inclusion criteria * stage iv or unresectable stage iii malignant melanoma or renal cell carcinoma. * melanoma * patients must have failed anti-pd-1/pd-l1 antibody therapy. * patients must have failed ipilimumab or be intolerant of ipilimumab and therefore unable to receive ipilimumab. * patients may, but are not obligated, to have failed high- dose il2. * braf status must be known or unable to be performed. if the melanoma expresses a braf mutation of v600e, v600k, or v600r patient must have received and progressed through a braf inhibitor or have failed that therapy due to toxicity. * renal cell carcinoma * patients must have failed anti-pd-1/pd-l1 antibody therapy. * patients must have failed a vegf pathway inhibitor and a second tyrosine kinase inhibitor. * patients may, but are not obligated, to have failed high- dose il2. * measurable disease based upon recist 1.1. * subjects with brain metastases will be eligible if the following are true: * subjects with ≤ 3 brain metastases * all metastases are ≤ 3 cm * all metastases have been treated and are asymptomatic * steroids are not required for management of the brain metastases * all metastases have been stable for 1 month following treatment * subjects with \> 3 brain metastases * all metastases are ≤ 3 cm * all metastases have been treated and are asymptomatic * steroids are not required for management of the brain metastases * all metastases have been stable for 6 months following treatment * performance status: ecog 0-1. * adequate organ function. * ability to provide informed consent. main exclusion criteria: * pregnancy * currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. * has a diagnosis of primary or secondary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 3 weeks prior to the first dose of trial treatment. replacement doses of steroids are permitted. * known history of active tb (bacillus tuberculosis) * hypersensitivity to pembrolizumab or any of its excipients. * known additional malignancies (exceptions dcis or lcis, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy). * prior anti-cancer monoclonal antibody (mab) within 3 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 3 weeks earlier. * prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent. * known carcinomatous meningitis. * active autoimmune disease that has required systemic treatment in the past 2 years. patients may be eligible if they have the following autoimmune diseases: thyroiditis or hypothyroidism, mild arthritis, diabetes, resolved hypophysitis, ulcerative colitis after total abdominal colectomy. * active infection requiring systemic therapy. * known psychiatric or substance abuse disorders. * known history of human immunodeficiency virus (hiv). * known active hepatitis b virus (hbv) or hepatitis c virus (hcv). * has received a live vaccine within 30 days of planned start of study therapy. * severe chronic pulmonary disease. * congestive heart failure, angina, or symptomatic cardiac arrhythmia or is classified according to the new york heart association classification as having class iii or iv heart disease. * history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

Keywords: pembrolizumab il-2 interleukin-2 mk-3475