Tislelizumab Plus Chemotherapy Improves PFS in Chinese Patients with NSCLC

Combining tislelizumab (BGB-A317) with chemotherapy improved progression-free survival (PFS) compared with chemotherapy alone as a frontline treatment in Chinese patients with advanced squamous non-small cell lung cancer (NSCLC), according to findings from the phase 3 BGB-A317-307 trial presented during the 2020 ASCO Virtual Scientific Program.¹

The multicenter, open-label, randomized, phase 3 trial included 360 patients from mainland China with untreated stage IIIb/IV squamous NSCLC, regardless of PD-L1 expression.

“The results from this phase 3 trial demonstrated that inhibiting the PD-1 pathway with tislelizumab, combined with standard chemotherapy, provided a clinically meaningful benefit to patients with advanced squamous NSCLC, as assessed by progression-free survival and response rates,” lead investigator Jie Wang, MD, PhD, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, said in a press release.² “Lung cancer is the leading cause of cancer-related death in China, and with NSCLC comprising the most common form of the disease, it is critical to identify new treatments that address patient needs.”

Patients were randomized in a 1:1:1 ratio to initial treatment with either 200 mg of tislelizumab every 3 weeks plus paclitaxel and carboplatin (arm A); 200 mg of tislelizumab every 3 weeks plus nab-paclitaxel and carboplatin (arm B); or paclitaxel and carboplatin (arm C). Paclitaxel, nab-paclitaxel, and carboplatin were administered for 4 to 6 cycles, and tislelizumab was administered until disease progression, intolerable toxicity, or treatment discontinuation. Crossover was allowed at disease progression for patients enrolled in the control arm.

The primary end point was PFS, with key secondary endpoints including objective response rate (ORR), duration of response, overall survival (OS), and safety.

Of the patients with PD-L1 expression <1%, the median PFS was 7.6 months in arm A and 5.5 months in the control arm (HR, 0.636; 95% CI, 0.368-1.101). The median PFS was 7.4 months in arm B (HR vs control, 0.692; 95% CI, 0.406-1.178).

Among patients with PD-L1 expression ranging from 1% to 49%, the median PFS was 7.6 months in arm A compared with 4.2 months in the control arm (HR, 0.439; 95% CI, 0.221-0.870). The median PFS was not evaluable in arm B (HR vs control, 0.311; 95% CI, 0.145-0.664).

In patients with PD-L1 expression >50%, the median PFS was 7.6 months in arm A compared with 5.5 months in the control arm (HR, 0.501; 95% CI, 0.282-0.891). The median PFS was 7.6 months in arm B (HR vs control, 0.425; 95% CI, 0.232-0.776).

The median PFS per Independent Review Committee (IRC) was 7.6 months when combining tislelizumab with paclitaxel and carboplatin versus 5.5 months in the control arm of paclitaxel and carboplatin alone (HR, 0.524; 95% CI, 0.370-0.742; P = 0.0001). The median PFS per IRC was also 7.6 months when combining tislelizumab with nab-paclitaxel (Abraxane) and carboplatin (HR vs control, 0.478; 95% CI, 0.336-0.679; P <.0001). The PFS benefit with tislelizumab was observed regardless of PD-L1 expression level. At a median follow-up of 8.6 months, the median overall survival (OS) had not yet been reached.

The ORR was 73% in arm A, 75% in arm B, and 50% in the control arm. The ORR in arm A comprised a 4% complete response (CR) rate and 68% partial response (PR) rate. The stable disease rate in the cohort was 15%, and 10% of patients had progressive disease. The ORR in arm B comprised a 3% CR rate and 72% PR rate. The stable disease rate in the cohort was 16% and 4% of patients had progressive disease.

Tislelizumab-related AEs across all grades occurred in 86.7% of arm A and 88.1% of arm B, respectively. Grade ≥3 tislelizumab-related AEs occurred in 36.7% and 40.7% of the 2 arms, respectively.

Serious treatment-related AEs (TRAEs) occurred in 27, 28, and 17 patients in arms A, B, and C, respectively. Serious TRAEs occurring in at least 2 patients in arm A and arm B included decreased neutrophil count (4 patients in each arm), febrile neutropenia (2 in arm A, 3 in arm B), leukopenia (2 and 1), increased blood creatine phosphokinase (0 and 2), decreased platelet count (1 and 2), bone marrow failure (2 and 1), and rash and pyrexia (2 in each arm). The most frequent serious TRAEs in the control arm were thrombocytopenia in 3 patients and decreased neutrophil count, decreased white blood cell count, and septic shock in 2 patients each.

TRAEs leading to death occurred in 1 patient in arm A, 2 in arm B, and 3 in the control arm, however none of the deaths were attributed solely to tislelizumab.

In April 2020, the China National Medical Products Administration accepted a supplemental new drug application (sNDA) for tislelizumab for use in combination with chemotherapy for the first-line treatment of patients with advanced squamous NSCLC. The sNDA is supported by the findings from the BGB-A317-307 trial.

References:

1. Wang J, Yu X , Lu S, et al. Phase III study of tislelizumab plus chemotherapy vs chemotherapy alone as first-line (1L) treatment for advanced squamous non-small cell lung cancer (sq NSCLC). Presented at: 2020 ASCO Virtual Scientific Program; May 29-31, 2020. Abstract 9554.

2. BeiGene Presents Phase 3 Data on Tislelizumab Combined with Chemotherapy for the Treatment of Patients with Advanced Squamous Non-Small Cell Lung Cancer at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program. Published May 29, 2020. https://bit.ly/36JuX3z. Accessed May 30, 2020.