Compared to chemotherapy, tislelizumab demonstrated a statistically significant and clinically meaningful improvement in overall survival in patients with previously treated, advanced or metastatic esophageal squamous carcinoma and a favorable safety profile

Tislelizumab also demonstrated a statistically significant and clinically meaningful improvement in overall response rate in patients with MSI-H or dMMR solid tumors and was generally well tolerated

CAMBRIDGE, Mass. & BEIJING--(BUSINESS WIRE)-- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, today announced clinical data from two pivotal trials of its anti-PD-1 antibody tislelizumab at the 2021 American Society of Clinical Oncology Annual Meeting (ASCO 2021), including the Phase 3 RATIONALE 302 trial of tislelizumab compared to chemotherapy in previously treated patients with advanced or metastatic esophageal squamous carcinoma (ESCC) and the pivotal Phase 2 trial of tislelizumab in patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch-repair-deficient (dMMR) solid tumors. ASCO 2021 takes place virtually on June 4-8, 2021.

“We are delighted to share the promising results from two pivotal trials of tislelizumab at this year’s ASCO, RATIONALE 302 in ESCC and a pivotal Phase 2 trial in MSI-H or dMMR solid tumors, which we plan to discuss with health authorities,” commented Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. “We and our collaborator Novartis are committed to advancing tislelizumab in a broad global clinical program both as a monotherapy and in combination with other cancer therapeutics. We hope that, with a growing body of clinical evidence, tislelizumab can become a meaningful immunotherapy that can potentially benefit more patients worldwide.”

Primary Results of RATIONALE 302 Trial of Tislelizumab vs. Chemotherapy in Previously Treated Advanced or Metastatic ESCC

Poster No. 4012

RATIONALE 302 is a randomized, open-label, multicenter global Phase 3 trial (NCT03430843) designed to evaluate the efficacy and safety of tislelizumab when compared to investigator’s choice chemotherapy as a second-line treatment for patients with advanced or metastatic ESCC. The primary endpoint is overall survival (OS) in the intent-to-treat (ITT) population; a key secondary endpoint is OS in patients with high PD-L1 expression (defined as visually-estimated combined positive score [vCPS] ≥10%); and other secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. A total of 512 patients were enrolled in the trial in 11 countries or regions across Asia, Europe, and North America, randomized 1:1 to either the tislelizumab arm or the chemotherapy arm (investigator’s choice of paclitaxel, docetaxel, or irinotecan).

“Advanced or metastatic ESCC typically has a poor prognosis, with the five-year survival rate estimated at five percent. In the RATIONALE 302 trial, tislelizumab significantly prolonged survival for these patients with consistent survival benefit observed across pre-defined subgroups, including PD-L1 expression and patient race,” commented Lin Shen, M.D., Peking University Cancer Hospital and Institute and a principal investigator of the trial. “In addition, tislelizumab demonstrated a favorable safety profile compared to chemotherapy, with no new safety signals identified. We hope that this anti-PD-1 antibody can become a new treatment option for those with advanced or metastatic ESCC following prior systemic treatment.”

At the data cutoff on December 1, 2020, the median follow-up time in the tislelizumab arm and the chemotherapy arm was 8.5 months and 5.8 months, respectively.

Tislelizumab demonstrated a statistically significant and clinically meaningful improvement in OS, compared to chemotherapy, in both the ITT population (primary endpoint) and in patients with high PD-L1 expression (key secondary endpoint). Efficacy results included:

• In the ITT population, the median OS in the tislelizumab arm was 8.6 months (95% CI: 7.5, 10.4), compared to 6.3 months (95% CI: 5.3, 7.0) in the chemotherapy arm (p=0.0001; hazard ratio [HR]=0.70 [95% CI: 0.57, 0.85]). The OS rates at six months and 12 months were 62.3% and 37.4% in the tislelizumab arm, respectively, compared to 51.8% and 23.7% in the chemotherapy arm;
• In patients with high PD-L1 expression, the median OS in the tislelizumab arm was 10.3 months (95% CI: 8.5, 16.1), compared to 6.8 months (95% CI: 4.1, 8.3) in the chemotherapy arm (p=0.0006; HR=0.54 [95% CI: 0.36, 0.79]). The OS rates at six months and 12 months were 67.4% and 44.0% in the tislelizumab arm, respectively, compared to 50.8% and 27.0% in the chemotherapy arm;
• In the trial, the PFS curves for two arms separate late. The median PFS was 1.6 months (95% CI: 1.4, 2.7) in the tislelizumab arm, compared to 2.1 months (95% CI: 1.5, 2.7) in the chemotherapy arm (HR=0.83 [95% CI: 0.67, 1.01]). The PFS rates at six months and 12 months were 21.7% and 12.7% in the tislelizumab arm, compared to 14.9% and 1.9% in the chemotherapy arm;
• Tislelizumab was associated was a higher ORR of 20.3% (95% CI: 15.6, 25.8), compared to 9.8% (95% CI: 6.4, 14.1) on chemotherapy, and
• Tislelizumab demonstrated a more durable anti-tumor response, with a median DoR of 7.1 months (95% CI: 4.1, 11.3), compared to 4.0 months (95% CI: 2.1, 8.2) on chemotherapy.

Compared to chemotherapy, tislelizumab demonstrated a favorable safety profile with no new safety signals identified. Safety results included:

• 244 patients (95.7%) experienced at least one treatment-emergent adverse event (TEAE) of any grade in the tislelizumab arm, compared to 236 patients (98.3%) in the chemotherapy arm;
• In the tislelizumab arm, 187 patients (73.3%) experienced at least one treatment-related adverse event (TRAE) of any grade, with the most common (≥10%) being aspartate aminotransferase (AST) increased (11.4%), anemia (11.0%), and hypothyroidism (10.2%);
• In the chemotherapy arm, 225 patients (93.8%) experienced at least one TRAE of any grade, with the most common (≥10%) being white blood cell count decreased (40.8%), neutrophil count decreased (39.2%), anemia (34.6%), decreased appetite (31.3%), diarrhea (27.5%), nausea (27.5%), vomiting (17.9%), alopecia (17.5%), malaise (14.6%), fatigue (13.8%), neutropenia (12.9%), leukopenia (12.5%), asthenia (11.7%), constipation (10.4%), and weight decreased (10.4%);
• Grade ≥3 TEAEs and TRAEs were reported in 118 patients (46.3%) and 48 patients (18.8%) in the tislelizumab arm, compared to 163 patients (67.9%) and 134 patients (55.8%) in the chemotherapy arm;
• Serious TEAEs and TRAEs were reported in 105 patients (41.2%) and 36 patients (14.1%) in the tislelizumab arm, compared to 105 patients (43.8%) and 47 patients (19.6%) in the chemotherapy arm;
• TEAEs or TRAEs leading to treatment discontinuation occurred in 49 patients (19.2%) and 17 patients (6.7%) in the tislelizumab arm, compared to 64 patients (26.7%) and 33 patients (13.8%) in the chemotherapy arm; and
• Death due to TEAEs or TRAEs occurred in 14 patients (5.5%) and five patients (2.0%) in the tislelizumab arm, compared to 14 patients (5.8%) and seven patients (2.9%) in the chemotherapy arm.

Results from Pivotal Phase 2 Trial in MSI-H or dMMR Solid Tumors

Poster No. 2569

This single-arm, open-label, multicenter pivotal Phase 2 trial (NCT03736889) was designed to evaluate the efficacy and safety of tislelizumab as a monotherapy in patients with previously treated, locally advanced unresectable or metastatic MSI-H or dMMR solid tumors, with an enrollment of 80 patients in China. The primary endpoint of this trial is ORR as assessed by independent review committee (IRC) per RECIST v1.1; secondary endpoints include time to response (TTR), DoR, disease control rate (DCR), and PFS as assessed by investigator and IRC, OS, and safety and tolerability.

“MSI-H and dMMR are found in many solid tumors, in particular cancers of the gastrointestinal tract, and existing literature supports a tissue-agnostic treatment approach with checkpoint inhibitors,” said Jian Li, M.D., Beijing Cancer Hospital and a principal investigator of the trial. “In this pivotal Phase 2 trial, we observed consistent responses across tumor types with tislelizumab and it was generally well tolerated. We will continue patient follow-up for longer term evaluation, and hope that tislelizumab could potentially become a new treatment option for patients with MSI-H/dMMR solid tumors.”

At the data cutoff on December 7, 2020, the median follow-up time was 11.78 months. Seventy-four patients were included in the primary efficacy analysis set, including 46 patients (62.2%) with colorectal cancer (CRC) and 28 patients with endometrial cancer, gastric or gastroesophageal junction (G/GEJ) cancer, and other tumor types.

Tislelizumab demonstrated a statistically significant and durable anti-tumor activity and showed consistent efficacy across tumor types, demonstrating the benefit of tissue-agnostic treatment. Efficacy results included:

• The ORR as assessed by IRC was 45.9% (95% CI: 34.3, 57.9; p