Abstract 1264P
Background
Tislelizumab, a monoclonal anti-PD-1 antibody, + chemotherapy was generally well tolerated and had antitumor activity in patients (pts) with advanced NSCLC.
Methods
In this open-label phase 3 study (NCT03594747), 360 Chinese pts with SQ NSCLC (randomized 1:1:1) received IV Q3W: tislelizumab 200 mg (D1) + paclitaxel 175 mg/m2 (D1) and carboplatin AUC 5 (D1) in Arm A; tislelizumab + nab-paclitaxel 100 mg/m2 (D1, 8, and 15) and carboplatin in Arm B; or paclitaxel and carboplatin in Arm C. Patients were stratified by disease stage (IIIB vs IV) and tumor cell PD-L1 expression (<1% vs 1-49% vs ≥50%) via VENTANA PD-L1 (SP263) Assay. The primary endpoint was PFS (RECIST v1.1) by Independent Review Committee; secondary endpoints included ORR, DoR, OS, and safety/tolerability. Association of blood tumor mutational burden (bTMB) with efficacy was explored.
Results
Combination therapy (Arms A and B) had significantly improved PFS and higher ORR/DoR vs chemotherapy (C). There was no association between PD-L1 expression and PFS or ORR (Table). With an optimized bTMB cutoff of 6 mut/Mb (selected by ROC), combination therapy improved PFS over chemotherapy in pts with high- (HR, 0.31; 95% CI: 0.14, 0.67) and low-bTMB (HR, 0.66; 95% CI: 0.27, 1.59). Median OS was not reached in any arm. Discontinuation of any treatment due to AEs was reported in 12.5%, 29.7%, and 15.4% of pts in Arms A, B, and C, respectively. The most common grade ≥3 AE was decreased neutrophil count, in line with known hematological toxicities of chemotherapy. Six treatment-related AEs led to death (n=1 [A]; n=2 [B]; n=3 [C]); none were solely attributed to tislelizumab Table: 1264P
| ITT Population N=360 | Arm A n=120 | Arm B n=119 | Arm C n=121 |
| Median PFS, mo | 7.6 | 7.6 | 5.5 |
| HRa | 0.52 | 0.48 | |
| P-valueb | 0.0001 | <0.0001 | |
| ORR, % | 72.5 | 74.8 | 49.6 |
| Median DoR | 8.2 | 8.6 | 4.2 |
| PD-L1 ≥50% N=125 | Arm A n=42 | Arm B n=42 | Arm C n=41 |
| Median PFS, mo | 7.6 | 7.6 | 5.5 |
| HRc | 0.50 | 0.43 | |
| ORR, % | 78.6 | 88.1 | 53.7 |
| PD-L1 1-49% N=91 | Arm A n=30 | Arm B n=30 | Arm C n=31 |
| Median PFS, mo | 7.6 | NE | 4.2 |
| HRc | 0.44 | 0.31 | |
| ORR, % | 70.0 | 66.7 | 41.9 |
| PD-L1 <1% N=144 | Arm A n=48 | Arm B n=47 | Arm C n=49 |
| Median PFS, mo | 7.6 | 7.4 | 5.5 |
| HRc | 0.64 | 0.69 | |
| ORR, % | 68.8 | 68.1 | 51.0 |
Abbreviations: DoR, duration of response; HR, hazard ratio; ITT, intention-to-treat; mo, months; NE, not evaluable; ORR, objective response rate; PFS, progression-free survival. aStratified; bOne-sided log-rank test; cNon-stratified.
.Conclusions
In pts with SQ NSCLC, combination therapy significantly improved clinical outcomes vs chemotherapy, regardless of PD-L1 expression and bTMB. The safety profile was similar to those of tislelizumab, chemotherapy, and underlying NSCLC, with no new safety signals.
Clinical trial identification
NCT03594747.
Editorial acknowledgement
Writing and editorial assistance was provided by Agnieszka Laskowski, PhD, and Elizabeth Hermans, PhD (OPEN Health Medical Communications, Chicago. IL), and funded by the study sponsor.
Legal entity responsible for the study
This study was sponsored by BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
S. Lu: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Speaker Bureau/Expert testimony: Hanseng; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Hutchison MediPharma; Advisory/Consultancy: Simcere. J. Zhang, L. Liang, X. Lin, X. Wu: Full/Part-time employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.