Abstract CT052: A phase IB study of mRNA-based active cancer vaccine, BI1361849, combined with durvalumab and tremelimumab immunotherapy in patients with non-small cell lung cancer (NSCLC)
Authors: Chen Dung-Tsa , Sabari Joshua , Thompson Jonathan , Niu Jiaxin , Mamdani Hirva , Thapa Ram , Thompson Zachary , Posina Thanmai , Ryan Aileen , Venhaus Ralph , Ricciardi Toni , Ramirez Kristen , Tanvetyanon Tawee , Gray Jhanelle 
Published: April 2024

Abstract
Introduction. BI1361849 is an RNA-based cancer vaccine, encoding for 6 tumor-associated antigens, including MUC1, survivin, NY-ESO-1, 5T4, MAGE-C2 and MAGE-C1, to balance systemic antigen-specific immune response. This open-label multicenter 2-arm Phase IB study evaluated the safety and preliminary efficacy of the addition of BI1361849 to durvalumab with or without tremelimumab for NSCLC.
Methods. Patients with metastatic NSCLC were enrolled in one of the two arms, Arm A: BI1361849 + durvalumab and Arm B: BI1361849 + durvalumab+ tremelimumab, to determine Recommended Combination Dose (RCD) for durvalumab according to a standard 3 + 3 design with a starting dose of 1500 mg and possible de-escalation to 750 mg, and a fixed total dose of BI1361849 at 960 μg and tremelimumab at 75 mg. Primary endpoints were safety and tolerability. Secondary endpoints were progression free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS), based on irRECIST and RECIST. Statistical analysis included descriptive statistics, Fisher exact test, and Kaplan-Meier method.
Results. A total of 57 patients were treated with 23 patients in Arm A and 34 patients in Arm B for safety analysis. Among them, 36 patients received at least 75% of the scheduled doses of durvalumab and tremelimumab and at least 4 vaccine doses in the first 2 cycles to meet efficacy analysis requirement with 17 patients in Arm A and 19 patients in Arm B. The RCD was durvalumab at 1500 mg, BI 1361849 at 960 μg, and tremelimumab at 75 mg. Both arms had comparable treatment related adverse events (56-57%) with generally low grade and manageable within current guidelines. Both arms had a comparable rate of treatment discontinuation (22-24%). For efficacy analysis, patients in Arm A had 29% ORR and 71% DCR, median months of 10, 7.3 5.7, and not reached for DOR, irPFS, PFS, and OS, respectively. In contrast, Arm B yielded 11% ORR and 53% DCR, median months of 6, 2.5, 2.5 and 10 for DOR, irPFS, PFS, and OS, respectively.
Conclusions. Overall, the doublet and triplet regimens were well tolerated. In comparison to recent published studies treated with durvalumab and/or tremelimumab, incorporation of BI1361849 to durvalumab yielded comparable or better treatment response, PFS, and OS than durvalumab alone or with chemotherapy. However, tremelimumab did not add clinical benefit.
Citation Format: Dung-Tsa Chen, Joshua Sabari, Jonathan Thompson, Jiaxin Niu, Hirva Mamdani, Ram Thapa, Zachary Thompson, Thanmai Posina, Aileen Ryan, Ralph Venhaus, Toni Ricciardi, Kristen Ramirez, Tawee Tanvetyanon, Jhanelle Gray. A phase IB study of mRNA-based active cancer vaccine, BI1361849, combined with durvalumab and tremelimumab immunotherapy in patients with non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT052.