Tislelizumab, an anti-PD-1 antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. In previous reports, tislelizumab was generally well tolerated and had antitumor activity in patients with advanced solid tumors.
This phase II study (BGB-A317-206; NCT03432598) assessed tislelizumab (200 mg Q3W) + platinum (plat)-based chemotherapy (Q3W) as first-line treatment for Chinese patients with advanced lung cancer. All patients received tislelizumab + plat doublet chemotherapy. Non-squamous (NSQ) NSCLC patients received plat + pemetrexed (PMX) for 4 cycles followed by PMX maintenance. Squamous NSCLC patients received 4-6 cycles of plat + paclitaxel (SQ-A) or plat + gemcitabine (SQ-B); SCLC patients received plat + etoposide. Response rate (RECIST v1.1), progression-free survival (PFS), overall survival (OS), and safety/tolerability were evaluated.
As of 31 Dec 2019, 54 patients (median age 61 yr; 74% male; 72% current/former smokers) received tislelizumab + chemotherapy. Median follow-up ranged from 15.5 (SCLC) to 25.3 mo (SQ-B). Response and survival are shown in the Table. Median PFS was 6.9 mo, 7.0 mo, 9.0 mo, and NE for the SCLC, SQ-A, NSQ, and SQ-B cohorts, respectively. Median OS was only reached in the SCLC cohort (15.5 mo; 95% CI: 11.8, NE). The most common grade ≥3 adverse events (AEs) were decreased neutrophil count (n=26) and anemia (n=10). Immune-related AEs were reported in 18 patients. One SQ-A patient experienced myocarditis with a fatal outcome after 1 tislelizumab dose. Table: 66P
|NSQ (n=16)||SQ-A (n=15)||SQ-B (n=6)||SCLC (n=17)|
|Median study follow-up, mo||23.0||24.2||25.3||15.5|
|Confirmed partial response, n||7||12||4||13|
|Stable disease, n||8||2||1||2|
|Progressive disease, n||1||0||0||1|
|ORR, % (95% CI)||44 (20, 70)||80 (52, 96)||67 (22, 96)||77 (50, 93)|
|DCR, % (95% CI)||94 (70, 100)||93 (68, 100)||83 (36, 100)||88 (64, 99)|
|OS rate at 24 mo, % (95% CI)||51 (23, 74)||65 (35, 84)||80 (20, 97)||31 (10, 55)|
|Median PFS, mo (95% CI)||9.0 (4.3, 21.4)||7.0 (5.5, 18.6)||NE (4.3, NE)||6.9 (4.9, 10.1)|
Abbreviations: CI, confidence interval; DCR, disease control rate; NE, not estimable; ORR, objective response rate.
In this phase II study, tislelizumab plus plat-based chemotherapy, as first-line treatment for advanced lung cancer, demonstrated preliminary antitumor activity including 24-mo OS rates of 51%, 65%, 80%, and 31% for patients in the NSQ, SQ-A, SQ-B, and SCLC cohorts. No new safety signals were identified.
Clinical trial identification
Writing and editorial assistance was provided by Stephan Lindsey, PhD, and Elizabeth Hermans, PhD (OPEN Health Medical Communications, Chicago, IL), and funded by the study sponsor.
Legal entity responsible for the study
S. Leaw: Shareholder/Stockholder/Stock options, Full/Part-time employment: BeiGene, Ltd. Y. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: BeiGene, Ltd. Y. Ma: Shareholder/Stockholder/Stock options, Full/Part-time employment: BeiGene, Ltd. W. Tan: Shareholder/Stockholder/Stock options, Full/Part-time employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.