Preliminary Analysis Demonstrates Durvalumab (Anti-PD-L1) & Lenalidomide Is Superior to Single-Agent Durvalumab (anti-PD-L1) in Refractory/Advanced Cutaneous T Cell Lymphoma in a Randomized Phase 2 Trial

Introduction: Mycosis fungoides (MF) and the leukemic variant Sézary syndrome (SS), commonly referred to as cutaneous T cell lymphoma (CTCL), are characterized by clonal expansion of malignant T cells in the skin within a background of chronic inflammation. Advanced stages have an unfavorable prognosis. The skin microenvironment plays an important role in the development and progression of MF and SS. We have shown that the malignant T cells escape immune surveillance via immune checkpoint signaling such as the PD-1/PD-L1 axis. In our phase I dose-escalating study anti-PD-L1 (durvalumab) & lenalidomide demonstrated a tolerable safety profile with significant clinical activity in refractory/advanced CTCL. We initiated the randomized Phase 2 portion to compare single agent durvalumab to durvalumab combined with lenalidomide in relapsed/advanced CTCL (NCT03011814). The primary end point was objective response rate (ORR) using the global composite response (based on skin, blood, nodes, and viscera) according to consensus guidelines. Secondary end points included duration of response, progression-free survival, and toxicity. Relationships between gene expression profile, tumor-microenvironment, and antitumor activity were exploratory end points. Methods:Adult patients with histologically confirmed MF or SS, who had failed ≥2 systemic therapies were enrolled and randomized 1:1 to single agent durvalumab (1500 mg (day 1 of 28-day cycle) or durvalumab (same dose) & lenalidomide (10 mg for cycle 1, 15 mg for cycle 2, then 20 mg for subsequent cycles daily for 21 days of each 28-day cycle). The study used a “pick a winner” design based on ORR. Serial skin and blood samples were collected to assess the impact on the tumor microenvironment (TME) and anti-tumor activity. Results:A total of 23 patients were randomized and had the following characteristics (11 durvalumab vs 12 durvalumab/lenalidomide): median age 57 yrs (35-79) vs 63 yrs (32-88); stage IB, 2 (18%) vs 4 (33%); stage IIB, 4 (36%) vs 3 (25%); stage III/IV, 5 (45%) vs 5 (42%); MF, 8 (73%) vs 8 (67%); e-MF/SS, 4 (36%) vs 2 (17%); large cell transformation 3 (27%) vs 5 (42%). The median number of prior systemic treatments for both single and combo arm was 3. Global best ORR was 58% for durvalumab/ lenalidomide vs 36% for durvalumab alone.Median follow up time was 7.9 (range, 0.9-27.6) months. Analysis is ongoing. One patient died one month after discontinuation from study due to PD. No serious AEs were observed