Abstract CT249: A phase 1b study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO)

Background: Immune checkpoint inhibitors (ICI) such as anti-PD-1/PD-L1 antibodies have rapidly become a pivotal approach to cancer therapy. Nivolumab is an anti-PD1 antibody approved for treatment of melanoma, lung, renal cell, head and neck squamous, urothelial and increasing number of other solid and hematological malignancies. However, patients with history of autoimmune disorders are excluded from the majority of clinical trials testing ICI. Consequently, the risks of flare ups and worsening of pre-existing autoimmune disorders in patients with tumor types who otherwise stand to benefit from ICI therapy are largely unknown, posing a challenge for oncologists. We are conducting a phase Ib study to test the hypothesis that nivolumab can be safely administered to patients with varying severity of Dermatomyositis, Systemic Sclerosis, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Inflammatory Bowel Disease, Multiple Sclerosis and others autoimmune disorders (AIM-Nivo). Methods: AIM-Nivo is an open-label, multi-center ongoing phase Ib study with nivolumab 480mg IV every 28 days in patients with autoimmune diseases and advanced or metastatic solid tumors. The study has autoimmune disease-specific cohorts overseen by a multidisciplinary group of experts. The primary objective is to assess the overall safety and toxicity profile of nivolumab in patients with autoimmune disorders and advanced or metastatic solid tumors. Secondary objectives are to evaluate the antitumor efficacy, the impact of nivolumab on the autoimmune disease severity indices, and to explore potential biomarkers of response, resistance or toxicity. Key overall inclusion criteria include age ≥18 years, histologically confirmed advanced or metastatic solid tumors in which ICI are approved or have shown clinical activity, Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Key overall exclusion criteria include prior therapy with an anti-PD-1/PD-L1 antibodies. Specific eligibility criteria are defined for each disease-specific cohort. For each autoimmune disorder, severity level of the disease as defined by disease-specific severity indices will be assessed, and up to a total of 12 patients will be included in each disease cohort at each severity level. Primary endpoints are dose-limiting toxicities defined for each autoimmune disease-specific cohort, adverse events (AEs) and serious AEs. Continuous monitoring of toxicity will be conducted. Key secondary endpoints are best objective response, progression free and overall survival and cohort specific tumor tissue, blood and non-tumor tissue-based biomarkers. The AIM-Nivo trial opened in May 2019 and is currently enrolling patients in the participating sites through the National Cancer Institute Experimental Therapeutics Clinical Trials Network (ETCTN). Clinical trial information: NCT03816345. Citation Format: Ecaterina E. Ileana Dumbrava, Maria Suarez-Almazor, Jeane Painter, Tanner M. Johanns, Michael L. Dougan, Laura Cappelli, Yinghong Wang, Clifton Bingham, Sarthak Gupta, Blake M. Warner, Osama Rahma, Jarushka Naidoo, Patrick A. Ott, David A. Hafler, Harriet Kluger, Arezou Khosroshahi, Rafeh Naqash, Lorinda Chung, Tamiko R. Katsumoto, Shivaani Kummar, Hussein Tawbi, Elad Sharon. A phase 1b study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT249.