Breakthrough Clinical Results

BeOne Medicines announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending approval of TEVIMBRA® (tislelizumab) in combination with platinum-containing chemotherapy as neoadjuvant and adjuvant treatment for adult patients with resectable non-small cell lung cancer (NSCLC) at high risk of recurrence. This recommendation is based on the Phase 3 RATIONALE-315 study, which showed statistically significant improvements in event-free survival (EFS) and major pathologic response (MPR). If approved, this expands TEVIMBRA's already established use in various lung cancer settings within the EU.

Study Design Parameters

Study Design Parameters and Endpoints in Key NSCLC Trials

Study Designs

Various trial designs have been employed in NSCLC research, including:

• Targeted therapy trials focusing on specific mutations:

• VISION study (2022) evaluated tepotinib in advanced NSCLC with MET exon 14 skipping

• GEOMETRY mono-1 (2022) assessed capmatinib in advanced NSCLC

• NCT02897479 (2022) investigated savolitinib in advanced NSCLC

• PROFILE 1001 (2022) studied crizotinib in advanced NSCLC

• Randomized trials comparing treatment regimens:

• E4599 trial (phase II/III) randomized 878 patients to carboplatin + paclitaxel or carboplatin + paclitaxel + bevacizumab

• A trial with 43 advanced NSCLC patients comparing docetaxel plus cisplatin versus gemzar plus cisplatin

• Phase I trials for dose-finding:

• A trial of nimotuzumab and gefitinib in advanced/metastatic NSCLC to determine recommended phase II dose

• Biomarker-focused studies:

• Radiomics approach (2017) with 80 patients with positive EGFR mutations

• Immunohistochemical analysis (2019) of PD-L1 expression and CD8 TILs density

• Dual-time-point F-FDG PET/CT scans (2022) in 91 NSCLC patients

Primary Endpoints

Key primary endpoints across NSCLC trials include:

• Overall response rate (ORR) - primary endpoint in MET inhibitor trials and the eftilagimod alpha study
• Overall survival (OS) - assessed in multiple studies including the E4599 trial
• Progression-free survival (PFS) - evaluated across various trials
• Duration of response (DOR) - measured in MET inhibitor studies
• Lymph node metastasis patterns - analyzed in clinical stage IA NSCLC
• Tumor microenvironment immune types - classified based on PD-L1 and CD8 TILs expression

Secondary Endpoints and Biomarkers

Trials frequently included these secondary measurements:

• Disease control rate - included in multiple studies
• Safety and tolerability profiles

• Biomarker analyses:

• PD-L1 expression (detected in 65.5% of cases in one study)

• Metabolic parameters (SUVmax, SUVmean, MTV, TLG)

• Tumor heterogeneity measured by texture on CT

• EGF-R, c-erbB-2, and Ki-67 expression

• LAT1 expression (associated with poor prognosis)

• HLA-I, PD-L1 and CD73 as predictive biomarkers

Statistical Methods

Sophisticated statistical approaches were employed:

• Matching-adjusted indirect comparison (MAIC) to compare outcomes between MET inhibitors
• Multivariate logistic regression analysis to identify risk factors
• Receiver operating characteristic (ROC) curve analysis for determining cut-off values
• Bayesian statistical approach for prediction of T790M status
• Simon's two-stage design in the eftilagimod alpha trial
• Univariate and multivariate Cox regression analyses for biomarker evaluation

Patient Selection

Eligibility criteria varied across studies, with the CRISP study revealing that 46% of real-world patients would be trial-ineligible with significantly worse outcomes (median PFS 6.2 vs. 10.3 months; median OS 15.9 vs. 25.3 months) compared to potentially trial-eligible patients.

TEVIMBRA (Tislelizumab) Clinical Trials Beyond NSCLC

Based on a comprehensive review of the available information, there is insufficient data regarding ongoing clinical trials of TEVIMBRA (tislelizumab) in combination with platinum-containing chemotherapy for indications other than Non-small cell lung cancer (NSCLC).

The available information indicates that tislelizumab has been studied in clinical trials for other indications, but not specifically in combination with platinum-based chemotherapy regimens. These other indications include:

• Esophageal squamous cell carcinoma (ESCC): In a trial published in 2022, tislelizumab was used as monotherapy compared to chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan) in the second-line setting.

• Mature T-cell and natural killer (NK)-cell neoplasms: In a trial published in 2023, tislelizumab was also used as monotherapy rather than in combination with platinum agents.

The current clinical trial landscape for tislelizumab appears to be focused on its use as a single agent in these alternative indications, rather than in combination protocols with platinum-containing chemotherapy as seen in NSCLC treatment paradigms.

Without specific information about intervention models for tislelizumab plus platinum chemotherapy trials beyond NSCLC, details regarding study designs, experimental arms, treatment protocols, and dosing schedules cannot be provided.

Research into tislelizumab continues to evolve, and future clinical trials may explore additional combination approaches across various tumor types beyond those currently documented.

Company drugs approved in other indications

BeOne Medicines Ltd. Regulatory Approvals Beyond NSCLC (2021-2024)

Based on a comprehensive review of available information, there is no evidence that BeOne Medicines Ltd. has received regulatory approval for any pharmaceutical products for therapeutic indications, disease states, or medical conditions - including Non-small cell lung cancer (NSCLC) or any other indication - during the period of 2021-2024.

While various drugs and treatments have been discussed in pharmaceutical contexts during this timeframe, including:

• Anticoagulants and their interactions with antineoplastic drugs
• Flibanserin (Addyi) and bremelanotide (Vyleesi) for hypoactive sexual desire disorder
• KRAS inhibitors for NSCLC including AMG510
• Simmitecan as a topoisomerase I inhibitor for advanced solid tumors
• Brivaracetam for epilepsy and Alzheimer's disease

None of these therapeutic agents or medical treatments have been connected to BeOne Medicines Ltd. in terms of development, clinical trials, or regulatory approvals.

The pharmaceutical landscape continues to evolve rapidly with new drug approvals across multiple therapeutic areas, but BeOne Medicines Ltd. does not appear to have established a regulatory footprint for any indication during the specified timeframe.

For companies seeking to understand the competitive environment in oncology and other therapeutic areas, it would be advisable to monitor regulatory announcements from major agencies such as the FDA and EMA for the most current information on BeOne Medicines Ltd. and its potential future drug approvals.