BeiGene’s Immunotherapy Drug Shines in Phase ESCC Trial

On January 27th, BeiGene announced that a Phase 3 trial that evaluated its anti-PD1 antibody, tislelizumab met its primary endpoint of overall survival (OS) as compared to chemotherapy in patients with advanced unresectable or metastatic ESCC who have received prior systemic treatment.

More importantly, the safety profile of tislelizumab was consistent with its known risks, and no other new safety concerns were identified.

“We are excited to announce the improved overall survival observed in another phase 3 trial for tislelizumab when compared to chemotherapy standard of care. This is our fourth positive Phase 3 readout for tislelizumab and the first from our large phase 3 program in gastrointestinal cancers that also include liver, stomach cancers as well as esophageal cancer,” stated Yong Ben, M.D., Chief Medical Officer, Immuno-Oncology, BeiGene.

ESCC

Esophageal squamous cell carcinoma (ESCC) is the most common subtype of esophageal cancer and ranks sixth in the leading causes of cancer-related deaths in the world.

The fatality of esophageal cancer is due to its rapid progress to advanced or metastatic state at the time of diagnosis, with a median survival of 8-10 months and an expected five-year survival rate of less than 5%. According to statistics, more than 600,000 new cases of esophageal cancer and about 550,000 deaths were reported last year.

“Esophageal cancer represents a significant unmet medical need with rapid progression and high mortality. Recent years have seen a paradigm shift in advanced ESCC treatment from chemotherapy and radiation to immunotherapy,” said Lin Shen, M.D., Vice President of Clinical Oncology at Beijing Cancer Hospital and lead investigator for the trial.

Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody that specifically reduces the binding to FcγR on macrophages. According to pre-clinical studies, the binding compromises the anti-tumor activity of PD-1 antibodies.

Tislelizumab is the first drug to emerge from BeiGene’s immuno-oncology biologics program. It rose to prominence after its international development as a monotherapy and its combination with other therapies for the treatment of a broad range of hematologic cancers and solid tumors.

RATIONALE 302 Trial

RATIONALE 302 is a randomized, open-label, multicenter, global Phase 3 trial designed to evaluate the effectiveness and safety of tislelizumab versus one of the three investigator-chosen chemotherapies paclitaxel, docetaxel, or irinotecan.

A total of 512 patients with tumor progression during or after first-line therapy for advanced unresectable or metastatic diseases, measurable disease, and ECOG performance status of 0 or 1, and adequate end-organ function were eligible to enroll and assigned in equal proportion to the two arms in the study. The patients were from 11 countries across Europe, Asia, and North America.

The success from the RATIONALE 302 trial was followed soon after by RATIONALE 303’s. In November 2020, BeiGene’s interim analysis on the RATIONALE 303 trial uncovered that tislelizumab helped the previously treated non-small cell lung cancer patients to live longer.

“The positive topline results from the RATIONALE 302 demonstrated that tislelizumab may offer a new treatment option for those living with this devastating disease and bring hope to patients and their families,” Dr. Shen added.

Business Perspective

Apart from the successes of the two clinical trials, tislelizumab has previously obtained approval from the China National Medical Products Administration (NMPA) for treating relapsed and refractory classical Hodgkin lymphoma and urothelial cancer.

In mid-January this year, BeiGene received $650 million from Novartis to collaborate on ex-China markets and regulations for tislelizumab. These advantages grant BeiGene more leverage to compete against other approved anti-PD-1 antibodies like Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo.

By Judy Ya-Hsuan Lin

Novartis Fortifies Immuno-Oncology Franchise with BeiGene Collaboration

References

1. https://ir.beigene.com/news-releases/news-release-details/beigene-announces-positive-topline-results-global-phase-3-trial?loc=us

Author

Judy Ya-Hsuan Lin

Success is the ability to go from one failure to another with no loss of enthusiasm.