BeiGene, Ltd. announced that the China National Medical Products Administration (NMPA) has granted its anti-PD-1 antibody tislelizumab approval for the first-line treatment of patients with advanced non-squamous non-small cell lung cancer (NSCLC) and conditional approval for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with at least one systemic therapy. NMPA Approval in First-Line Advanced Non-Squamous NSCLC: The approval of tislelizumab for the first-line treatment of patients with advanced non-squamous NSCLC was supported by clinical results from a Phase 3 trial (NCT03663205) of tislelizumab in combination with pemetrexed and platinum chemotherapy (either carboplatin or cisplatin) in patients with stage IIIB or stage IV non-squamous NSCLC, compared to pemetrexed and platinum alone. A total of 334 patients in China were enrolled in the trial, randomized 2:1 to either the tislelizumab and chemotherapy arm or the chemotherapy arm.

As announced in April 2020, the trial met the primary endpoint of statistically significant improvement in progression-free survival (PFS), as assessed by independent review committee (IRC), in the pre-planned interim analysis. The safety profile of tislelizumab in combination with chemotherapy was consistent with the known risks of each study treatment, and no new safety signals were identified. The results of the interim analysis of the trial were presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 in September 2020.

NMPA Approval in Second- or Third-Line HCC: The NMPA conditional approval of tislelizumab in patients with HCC who have received at least one systemic therapy is based on clinical results from a single-arm, open-label, multicenter, global pivotal Phase 2 trial (NCT03419897) conducted in 249 patients from eight countries and regions in Asia and Europe, including 138 patients (55.4%) who received one line of prior systemic therapy and 111 patients (44.6%) who received at least two lines of prior therapies. Of all the patients enrolled in the trial, the median age was 62 years and 63.9% of patients had history of viral hepatitis, with hepatitis B accounting for the majority (51.4%) followed by hepatitis C (14.5%). With a median follow-up time of 12.4 months, objective response rate (ORR) as assessed by IRC per RECIST v1.1 was 13.3% (95% CI: 9.3, 18.1), including three complete responses (CRs); disease control rate (DCR) was 53.0% (95% CI: 46.6, 59.3); among patients who achieved a CR or partial response (PR), 90.4% (95% CI: 73.1, 96.8) and 79.2% (95% CI: 59.3, 90.2) of them sustained response at six months and 12 months, respectively.

Median overall survival (OS) was 13.2 months (95% CI: 10.8, 15.0) and PFS was 2.7 months (95% CI: 1.4, 2.8). The safety profile of tislelizumab as a monotherapy in the label in China was based on 1,183 patients who received tislelizumab as a monotherapy in five clinical trials, including the pivotal Phase 2 trial in HCC. The most common adverse reactions (=10%) were aspartate aminotransferase (AST) increased, alanine aminotransferase (ALT) increased, rash, and fatigue.

Grade =3 adverse reactions occurred in 17.3% of patients, with the most common (=1%) being AST increased, ALT increased, gamma-glutamyltransferase increased, anemia, pneumonitis, and lung infection. For tislelizumab as a monotherapy, the most common immune-mediated adverse reactions were immune-mediated pneumonitis, diarrhea and colitis, hepatitis, nephritis, endocrinopathies (hypothyroidism, hyperthyroidism, thyroiditis, adrenocortical insufficiency, and hyperglycemia and Type 1 diabetes mellitus), skin adverse reactions, pancreatitis, myocarditis, and myositis.