ESMO 2017: Phase Ib/II Trial of Interleukin-2 and Nivolumab in Metastatic Clear Cell Renal Cell Cancer

Madrid, Spain ( At today’s ESMO 2017 poster session, Dr. Yentz and colleagues at the University of Michigan presented their trial design for assessing Interleukin-2 (IL-2) and nivolumab for patients with metastatic clear cell renal cell carcinoma (RCC). Despite the many systemic therapy advances for patients with metastatic RCC, high dose IL-2 immunotherapy remains a standard therapy for suitable patients with metastatic clear cell RCC who have good performance status. High dose IL-2 is unique among RCC therapies in eliciting durable complete responses (DCR) in a select group of patients (7-9%). IL-2 promotes early steps in the lymphocyte activation cascade, increases trafficking of cytotoxic T lymphocytes to the tumor and induces Th1 differentiation of CD4 T helper cells. There is an urgent need to evaluate high dose IL-2 combination therapies that could increase the response proportion. Nivolumab, an immune checkpoint inhibitor, blocks the interaction between PD-1 on activated T cells and its ligands that are expressed on immune cells and tumor cells. The objective of this phase 1b/II clinical trial is to assess the combination of high dose IL-2 and a PD-1 inhibitor for patients with metastatic clear cell RCC. The hypothesis is that high dose IL-2 may elicit a potent synergistic anti-cancer immune response reflected in improved response proportion and survival with acceptable toxicity.

Trial design: This multi-site phase Ib/II trial will determine safety and efficacy of high dose IL-2 in combination with nivolumab for patients with metastatic RCC. Key inclusion criteria include: (i) patients with metastatic clear cell RCC, (ii) 0-2 prior systemic therapies, and (iii) candidates for high dose IL-2 and nivolumab. These patients will be treated with high dose IL-2 (600,000 IU/kg/dose every 8 hours for up to 14 doses) on Days 1-5 and again on Days 15-19, with nivolumab (240 mg IV every 14 days) starting on Day 8 +/- 3 weeks. Patients will continue on nivolumab every 2 weeks for up to 48 weeks barring intolerable toxicities or consent withdrawal or progressive disease. Nivolumab may potentially be continued beyond first progression. The primary objective/endpoint of the phase 1b portion of the trial is safety of the combination/immune mediated grade 3/4 events of interest. The primary endpoint of the phase II portion of the trial is the overall response proportion as assessed by RECIST 1.1. Secondary endpoints are (i) safety/toxicity, (ii) overall survival, and (iii) progression free survival at two years. The planned accrual is for 23 evaluable patients over two years. Whole blood and serum will be analyzed for circulating immune cell repertoire and baseline tumor tissue will be sequenced. Clinical trial identification: NCT02989714

Speaker: Sarah Yentz, University of Michigan, Ann Arbor, United States of America

Co-Authors: A. Alva (Ann Arbor, United States of America)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain