FDA Gives Green Light to Novel Immunotherapy Combination

BeiGene, Ltd., a global oncology powerhouse soon to be known as BeOne Medicines Ltd., has achieved a significant milestone in cancer treatment. The U.S. Food and Drug Administration (FDA) has granted approval for TEVIMBRA® (tislelizumab-jsgr) in combination with platinum and fluoropyrimidine-based chemotherapy. This approval is specifically for the first-line treatment of adults with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma (G/GEJ), whose tumors express PD-L1 (≥1).

Mark Lanasa, M.D., Ph.D., Chief Medical Officer for Solid Tumors at BeiGene, expressed enthusiasm about this development. He emphasized that this approval, the second for TEVIMBRA in the United States this year, underscores its potential to address critical needs in oncology. Dr. Lanasa also acknowledged the invaluable contributions of patients, clinicians, and researchers in making this progress possible.

The FDA’s decision was based on the results of the RATIONALE-305 trial (NCT03777657), a global Phase 3 study. This randomized, double-blind, placebo-controlled trial evaluated TEVIMBRA’s efficacy and safety in combination with chemotherapy for first-line treatment of advanced G/GEJ cancer. The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful overall survival (OS) benefit. Patients treated with TEVIMBRA plus chemotherapy showed a median OS of 15.0 months, compared to 12.9 months for those receiving placebo plus chemotherapy. This translated to a 20% reduction in the risk of death.

The safety profile of TEVIMBRA was assessed using pooled data from 1,972 patients across multiple studies. The most common Grade 3 or 4 adverse reactions for TEVIMBRA in combination with chemotherapy included neutropenia, thrombocytopenia, anemia, and various other side effects.

TEVIMBRA has also received FDA approval as a monotherapy for adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) who have undergone prior systemic chemotherapy without a PD-(L)1 inhibitor. Additionally, a Biologics License Application (BLA) is under FDA review for its use in first-line treatment of locally advanced unresectable or metastatic ESCC in adults.

BeiGene’s recent announcement of its intent to rebrand as BeOne Medicines Ltd. reaffirms its commitment to developing innovative cancer treatments through global partnerships, aiming to serve as many patients as possible.

Commentary by SuppBase columnist Alice Winters:

The recent FDA approval of TEVIMBRA (tislelizumab-jsgr) for gastric and gastroesophageal junction cancers marks a significant advancement in the field of oncology, particularly for patients with limited treatment options. This approval underscores the growing importance of immunotherapy in cancer treatment strategies.

From a scientific standpoint, TEVIMBRA’s mechanism of action as a PD-1 inhibitor is noteworthy. By blocking the PD-1 pathway, it potentially enhances T-cell responses against tumor cells. The combination with chemotherapy suggests a synergistic approach, potentially offering a more robust anti-tumor effect than either treatment alone.

The RATIONALE-305 trial results are particularly impressive. A 2.1-month improvement in median overall survival might seem modest at first glance, but in the context of advanced gastric cancer, where survival gains are often measured in weeks, this represents a clinically meaningful benefit. The 20% reduction in the risk of death is a statistically significant outcome that could translate to real-world improvements in patient care.

However, it’s crucial to consider the safety profile. The list of Grade 3 or 4 adverse reactions is extensive, including serious conditions like neutropenia and pneumonitis. This highlights the need for careful patient selection and monitoring during treatment. The balance between efficacy and toxicity will be a key consideration for oncologists when deciding on treatment plans.

The approval’s specificity for PD-L1 positive tumors (≥1) is an important aspect. This biomarker-driven approach aligns with the trend towards personalized medicine in oncology. However, it also raises questions about treatment options for patients whose tumors do not express PD-L1, emphasizing the ongoing need for diverse treatment strategies.

From a market perspective, TEVIMBRA’s approval in multiple indications within a short timeframe is impressive. It positions BeiGene (soon to be BeOne Medicines) as a significant player in the competitive landscape of cancer immunotherapies. The company’s focus on global partnerships and patient access is commendable, though the real-world implementation of these goals remains to be seen.

In conclusion, while TEVIMBRA represents a valuable addition to the oncology armamentarium, its long-term impact will depend on real-world effectiveness, management of side effects, and accessibility to patients. As with any new cancer therapy, post-marketing surveillance and further clinical studies will be crucial to fully understand its place in treatment paradigms. The oncology community will be watching closely as this promising therapy moves from clinical trials to standard practice.