Targeting Autophagy and Immunotherapy with Hydroxychloroquine and Interleukin 2 in Patients with Metastatic Renal Cell Carcinoma (mrcc): A Cytokine Working Group Study.

106 Background: We performed a Phase II study of the combination of the autophagy inhibitor, hydroxychloroquine (HCQ), along with high dose IL-2 in patients with advanced renal cancer. 31 patients were entered on this Cytokine Working Group Study conducted at six member institutions;NCT01550367. This combination in murine models was associated with diminished toxicity and increased efficacy, and, in preliminary studies, diminished high mobility group box 1 (HMGB1) protein, consistent with its established role in serving as a Damage Associated Molecular Pattern (DAMP) molecule and inducer of autophagy. Methods: The Study Design involved initiating oral Hydroxychloroquine 300 mg P.O bid. Aldesleukin (600,000 IU/kg) was administered q8hrs in courses consisting of two cycles separated by 7-14 days and constituting a single course. For patients with stable or responsive disease, additional courses were administered every approximately 85-90 days. Serum, plasma, Paxgene tubes, and peripheral blood mononuclear cells were obtained sequentially prior to therapy initiation and sequentially on D1 and D2 of each cycle following initiation of therapy. Results: 31 patients (9F, 22M) have been registered and 3 confirmed complete responses observed; the current median overall survival has not been reached in the 29pts. The Baseline Karnofsky Score of 100 (17pts), 90 (13pts), and 80(1 pt). The mean age was 57.5 years, range = (45.2, 68.8). 26 patients had a mean of 12.5 doses +/-4.7 (3, 23) with 13 pts receiving a second course and 4, a third. Platelet nadir was diminished from baseline by 26%. Of the 27 patients in the data set, 18 had at least one Grade 4 toxicity at least possibly related to treatment, and 9 patients had at least one Grade 3 adverse event at least possibly related to treatment but no Grade 4 events.Serologic and cellular data and complete clinical data will be submitted with the completed abstract. Conclusions: The combination of high dose aldesleukin and daily oral HCQ was well tolerated. We have concluded this trial and will report mature survival data, toxicity data, and biomarkers/autophagy measures with the final submission. Clinical trial information: NCT01550367.