A phase 1b study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO).
Authors: Dumbrava Ecaterina Elena , Dougan Michael L. , Gupta Sarthak , Cappelli Laura , Katsumoto Tamiko R. , Rahma Osama E. , Painter Jeane , Wang Yinghong , Suarez-Almazor Maria E. , Reid Pankti , Wesley Sarah F. , Hafler David A , Bingham Clifton O. , Warner Blake M , Chung Lorinda , Ott Patrick Alexander , Kluger Harriet M. , Khosroshahi Arezou , Tawbi Hussein Abdul-Hassan , Sharon Elad 
Published: June 2021

TPS2676 Background: Nivolumab is an anti-PD1 monoclonal antibody approved for treatment of an increasing number of solid tumors and hematological malignancies. However, patients (pts) with history of autoimmune disorders are excluded from the majority of clinical trials testing immune-checkpoint inhibitors (ICI) such as anti-PD1/anti-PD-L1 antibodies. Consequently, the risks of flare ups, worsening of pre-existing autoimmune disorders or risk of de-novo immune related adverse events (irAEs) in pts with dysfunctional immune systems and 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 pts with varying severity of Dermatomyositis, Systemic Sclerosis, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Inflammatory Bowel Disease, Multiple Sclerosis and other 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 pts with autoimmune diseases and advanced malignancies (NCT03816345). 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 pts with autoimmune disorders and advanced malignancies. 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 for each of the autoimmune disease-specific cohorts. Key overall inclusion criteria include age ≥18 years, histologically confirmed advanced or metastatic malignancies in which ICI are approved or have shown clinical activity. Key overall exclusion criteria include prior therapy with 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 pts will be included in each disease cohort at each severity level (max 36 pts per cohort). Primary endpoints are dose-limiting toxicities, adverse events (AEs) and serious AEs. Continuous monitoring of toxicity will be conducted. Key secondary endpoints are best objective response per RECIST1.1; 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 enrolling pts through the National Cancer Institute Experimental Therapeutics Clinical Trials Network (ETCTN), Early Drug Development Opportunity Program (EDDOP), and Create Access to Targeted Cancer Therapy for Underserved Populations (CATCH-UP) sites. Clinical trial information: NCT03816345.