A Phase 2 Study of Tislelizumab in Combination With Platinum-Based Chemotherapy as First-line Treatment for Advanced Lung Cancer in Chinese Patients
Mené en Chine sur 54 patients atteints d’un cancer du poumon de stade avancé, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse objective, et la toxicité d’un traitement de première ligne combinant tislélizumab (un anticorps anti-PD-1) et chimiothérapie à base de sels de platine
Résumé en anglais
Objectives : This phase 2 study explored tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy as first-line treatment of advanced lung cancer. Material and Methods : Eligible patients had histologically/cytologically confirmed advanced/metastatic nonsquamous non-small cell lung cancer (NSQ), squamous NSCLC (SQ), or extensive-stage small cell lung cancer (SCLC). All patients received tislelizumab 200?mg in combination with 4–6 cycles of platinum-doublet. The NSQ cohort received pemetrexed?+?platinum Q3W for 4 cycles followed by pemetrexed maintenance, the SQ cohort received paclitaxel?+?platinum (A) or gemcitabine?+?platinum (B) Q3W, and the SCLC cohort received etoposide?+?platinum Q3W. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Progression-free survival (PFS) and tolerability profile were secondary endpoints; exploratory endpoints included overall survival (OS) and predictive biomarkers. Results : Fifty-four patients (NSQ, n?=?16; SQ?=?21 [SQ-A, n?=?15; SQ-B, n?=?6]; SCLC, n?=?17) were enrolled; as of February 25, 2019, 14 remained on treatment. Confirmed ORRs were 44% (NSQ), 80% (SQ-A), 67% (SQ-B), and 77% (SCLC). Median PFS were 9.0 months (NSQ), 7.0 months (SQ-A), and 6.9 months (SCLC); PFS in SQ-B are not mature. Median OS was not reached in all cohorts except for SCLC (15.6 months). Common treatment-emergent AEs included anemia (79.6%, n?=?43) and decreased white blood cell count (74.1%, n?=?40). Gene expression analyses revealed distinct patterns by histology type; lower tumor inflammation signature levels were observed among nonresponding patients with NSQ and SCLC. Conclusions : Tislelizumab plus chemotherapy demonstrated encouraging antitumor activity, was generally well tolerated, and distinct immune- and cell cycle–related gene signatures were associated with efficacy across cohorts.
