Phase 3 BGB-A317-307 trial results showed statistically significant improvements in progression-free survival with tislelizumab plus chemotherapy versus chemotherapy alone in Chinese patients with untreated advanced squamous non–small cell lung cancer.
Statistically significant improvement in progression-free survival (PFS) was seen with tislelizumab (BGB-A317) plus chemotherapy versus chemotherapy alone in Chinese patients with untreated advanced squamous non–small cell lung cancer (NSCLC), according to findings from the phase 3 BGB-A317-307 trial. These data were presented as part of the 2020 American Society of Clinical Oncology Virtual Scientific Program.1
The median PFS per Independent Review Committee (IRC) was 7.6 months when combining the anti–PD-1 agent 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 = .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 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, stated 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.”
The multicenter, open-label, randomized, phase 3 BGB-A317-307 trial included 360 patients from mainland China with untreated stage IIIb/IV squamous NSCLC, regardless of PD-L1 expression. Patient characteristics were well balanced among the study arms. The median patient age was 62 years (range, 34-74), with 35.3% of patients aged ≥65 years. Most (91.7%) patients were male, former tobacco users (63.6%), and had an ECOG performance status of 1 (76.4%).
Overall, 66.1% of patients had stage IV disease and 33.9% had stage IIIb. The most common confirmed distant metastatic sites included bone (16.9%), liver (12.2), and brain (1.7%). Forty percent of patients had <1% PD-L1 expression on tumor cells, 25.3% had 1% to 49% expression, and 34.7% had ≥50% expression.
Patients were randomized in a 1:1:1 ratio to initial treatment with either tislelizumab (200 mg every 3 weeks) plus paclitaxel and carboplatin (arm A); tislelizumab (200 mg 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 end points including objective response rate (ORR), duration of response, OS, and safety.
Among 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). And 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 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.
The most frequent cause of treatment discontinuation was progressive disease (16.7%), followed by adverse events (AEs; 6.7%), and withdrawal of consent (4.7%).
Tislelizumab-related adverse events (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 AEs 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. None of the deaths were attributed solely to tislelizumab.
In April 2020, the China National Medical Products Administration has accepted a supplemental new drug application (sNDA) for the PD-1 inhibitor 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.