Abstract 246: Phase 1 study: Ipilimumab (anti CTLA-4) in combination with Lenalidomide in patients with advanced cancers

Abstract

Abstract Background: Ipilimumab, a cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibody potentiates an antitumor T-cell response. Lenalidomide, a derivative of thalidomide possesses immunomodulatory, antiangiogenic, and antineoplastic properties and thereby inhibits the growth of blood vessels and exhibits an anti-inflammatory effect. The potential synergistic effect of stimulating one's own immune system to attack cancer in combination with depriving further tumor growth provides rationale for combining Ipilimumab and Lenalidomide. Methods: We designed a phase I study (3+3 design) to determine the safety of Ipilimumab (1.5-3mg/kg IV q 28 days x 4) and Lenalidomide (10-25mg PO daily x 21 q 28 days) until disease progression or unacceptable toxicity in advanced cancers. Endpoints included maximum tolerated (MTD), dose limiting toxicities (DLT), safety, and response per immune response criteria (iRC). Results: To date, 21 patients (men, n = 8; women, n = 13), median age 56 (19-75) years, median of 3 (0-6) prior therapies (including 3 patients with prior ipilimumab) were enrolled in 3 of 5 dose levels ranging from 1.5-3mg of Ipilimumab and Lenalidomide 10-15 mg. The MTD has not been reached yet. DLT included grade (G) 3 macular rash in 2 patients (dose levels 2 and 3) and G3 pancreatitis (dose level 2). Other G3/4 drug related toxicities included G4 hypopituitarism (n = 1) and G3 pulmonary embolism (n = 1). Of 21 treated patients, 11 (52%) patients had stable disease. The median change in size of target lesions per iRC was 13% (-44% to +86%) with 5 (24%) of patients with at least -10% shrinkage (Hodgkin lymphoma, n = 2; melanoma, n = 1; follicular thyroid carcinoma, n = 1; teratoma, n = 1) lasting for 0.9 to 12.3+ months. The median time-to-treatment failure was 2.1 months (95% CI 1.4-2.8). Conclusion: Ipilimumab and Lenalidomide have manageable side effect profile and demonstrate possible activity in patients with refractory Hodgkin lymphoma, melanoma, follicular thyroid cancer and teratoma. Citation Format: Divya Sakamuri, Sonia L. Betancourt Cuellar, Isabella C. Glitza, Siqing Fu, Jennifer J. Wheler, Gerald S. Falchook, Apostolia M. Tsimberidou, David S. Hong, Vivek Subbiah, Michelle A. Fanale, Maria E. Cabanillas, Funda Meric-Bernstam, Filip Janku. Phase 1 study: Ipilimumab (anti CTLA-4) in combination with Lenalidomide in patients with advanced cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 246. doi:10.1158/1538-7445.AM2015-246