Authors: Delvys Rodriguez-Abreu, Melissa Lynne Johnson, Maen A. Hussein, Manuel Cobo, Anjan Jayantilal Patel, Nevena Milica Secen, Ki Hyeong Lee, Bartomeu Massuti, Sandrine Hiret, James Chih-Hsin Yang, Fabrice Barlesi, Dae Ho Lee, Luis G. Paz-Ares, Robert Wenchen Hsieh, Karen Miller, Namrata Patil, Patrick Twomey, Amy V. Kapp, Raymond Meng, Byoung Chul Cho; Hospital Universitario Insular de Gran Canaria, Las Palmas De Gran Canaria, Spain; Sarah Cannon Research Institute, Nashville, TN; Florida Cancer Specialists, Sarasota, FL; UGC Oncología Intercentros, Hospitales Universitarios Regional y Virgen de la Victoria de Malaga, Instituto de Investigaciones Biomédicas de Málaga (IBIMA), Málaga, Spain; Institute for Pulmonary Diseases, Novi Sad, Vojvodina, Serbia; Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea; Alicante University Hospital ISABIAL, Alicante, Spain; Institut de Cancérologie de l’Ouest, Saint-Herblain, France; National Taiwan University Hospital, Taipei, Taiwan; Aix Marseille University, CNRS, INSERM, Marseille, France; University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; Hospital Universitario 12 de Octubre, Madrid, Spain; Stanford Hosp and Clinics, Sunnyvale, CA; Genentech, South San Francisco, CA; Genentech, Inc., South San Francisco, CA; Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
Research Funding: Genentech, Inc.
Background: The immunomodulatory receptor TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers, including NSCLC. In a phase I study (GO30103), co-inhibition of TIGIT and PD-L1 signaling with tira plus atezo in CIT-naïve PD-L1 positive NSCLC potentially improved overall response rates (ORR) compared to historical ORR with PD-L1/PD-1 inhibitors. We conducted this phase II trial to confirm the efficacy and safety of tira plus atezo (TA) compared to placebo plus atezo (PA) in 1L NSCLC (GO40290, NCT NCT03563716).
Methods: This prospective, randomized, double-blind, placebo-controlled trial enrolled patients (pts) with chemotherapy-naïve PD-L1+ (TPS ≥ 1% by 22C3 IHC pharmDx Dako assay) locally advanced or metastatic NSCLC with measurable disease, ECOG PS 0-1, and without EGFR or ALK alterations. Pts were randomized 1:1 to TA (tira 600 mg IV plus atezo 1200 mg IV) or PA (placebo plus atezo 1200 mg IV) on day 1 of every 3-week cycle. Stratification factors were PD-L1 status (TPS ≥ 50% vs TPS 1-49%), histology, and tobacco history. Co-primary endpoints were investigator assessed ORR and PFS, and additional endpoints were duration of response (DOR), OS, and safety. Exploratory endpoints were the effect of PD-L1 status on ORR and PFS.
Results: 135 pts were randomized to PA (n = 68) or TA (n = 67). At primary analysis (30 Jun 2019), TA improved ORR and median PFS (mPFS) compared to PA, with median follow-up of 5.9 mo. In the safety population (68 in PA, 67 in TA), treatment-related AEs (TRAEs) occurred in 72% (PA) and 80.6% (TA); Grade ≥3 TRAEs occurred in 19.1% (PA) and 14.9% (TA). AEs leading to treatment withdrawal occurred in 10.3% (PA) and 7.5% (TA). Clinical trial information: NCT03563716. With an additional six months of follow-up since the primary analysis (2 Dec 2019, median follow-up of 10.9 mo), improvement in ORR and mPFS was maintained in ITT for TA (37.3% [25.0, 49.6] and 5.6 mo [4.2, 10.4]) vs PA (20.6% [10.2, 30.9] and 3.9 mo [2.7, 4.5]). The safety profile remained tolerable.
Conclusions: Treatment with TA compared to PA showed clinically meaningful improvement in ORR and PFS in ITT. The safety profile of TA was similar to PA.