As Novartis and BeiGene wait for a delayed FDA decision on what could be tislelizumab’s first U.S. approval, the PD-1 inhibitor has chalked up another clinical win. But how much that trial success matters in a potential fight against Roche’s first-to-market Tecentriq remains an open question.
The latest trial win showed that tislelizumab matched up to Bayer’s aging Nexavar at extending the lives of patients with newly diagnosed unresectable liver cancer, BeiGene said Tuesday.
The current global phase 3 Rationale 301 trial is “intended to support global registrations,” a BeiGene spokesperson told Fierce Pharma. The spokesperson didn’t directly answer whether a filing for tislelizumab monotherapy in frontline liver cancer is planned, but said the company will share details on its regulatory approach in collaboration with Novartis “in due course.”
Rationale 301’s design was an outlier in today’s newly diagnosed liver cancer landscape as other PD-1/L1 trials have focused on a combination approach. Back in 2020, Roche’s Tecentriq, used in tandem with anti-VEGF drug Avastin, became the first PD-1/L1 inhibitor approved in previously untreated liver cancer. That approval was based on phase 3 data showing the combo cut the risk of death by 41% over Bayer’s Nexavar, an old standard of care.
Tecentriq remains the only PD-1/L1 drug with a frontline liver cancer nod from the FDA. Merck tried for the indication with a cocktail of its Keyturda and Eisai-partnered Lenvima, but that pair failed to beat Lenvima alone at preventing deaths or tumor progression.
Earlier this year, China’s Jiangsu Hengrui Medicine said its PD-1 inhibitor camrelizumab and VEGFR inhibitor apatinib, also known as rivoceranib, topped Nexavar at both prolonging patients’ life span and stalling disease progression or death in a global phase 3 trial. Hengrui at that time said it planned to start a conversation with the FDA for a potential application in newly diagnosed liver cancer and has since launched Luzsana Biotechnology to focus on the global market.
Years ago, Bristol Myers Squibb’s phase 3 CheckMate-459 trial showed Opdivo alone didn’t significantly improve overall survival compared with Nexavar. After failing to demonstrate superiority in the frontline setting, BMS last year decided to voluntarily withdraw Opdivo’s accelerated approval as a second-line liver cancer therapy.
With all those results, it’s hard to imagine how tislelizumab’s monotherapy trial with a Nexavar noninferiority design could win over the FDA.
Still, BeiGene devised tislezliumab’s monotherapy trial in consultation with drug regulators, the company’s R&D head Lai Wang, Ph.D., said during a Q&A with Chinese investors in May. BeiGene believes PD-1 and VEGFR combinations could be the main therapy for first-line liver cancer in the near term, he added.
BeiGene also has PD-1/VEGFR trials underway in liver cancer, Wang pointed out. These include a small phase 2 trial of tislelizumab combined with Lenvima, and a phase 2 trial pairing tislezliumab with a biosimilar of Avastin and BeiGene’s anti-TIGIT candidate ociperlimab. The Avastin biosimilar was developed by China’s Bio-Thera Solutions and was recently out-licensed to Novartis’ Sandoz. BeiGene also has a collaboration pact with Novartis on ociperlimab.
Tislelizumab’s monotherapy liver cancer readout comes after BeiGene and Novartis were hit an FDA delay on the PD-1 inhibitor’s very first U.S. decision in previously treated esophageal squamous cell carcinoma. Novartis has also planned for a U.S. submission in frontline nasopharyngeal cancer this year but recently scrapped a tislelizumab monotherapy U.S. filing in newly diagnosed non-small cell lung cancer after feedback from the FDA.
BeiGene is building an oncology franchise around two disease areas, Wang told Fierce Biotech in a recent interview. One is B-cell malignancy, and the other is solid tumors with a focus on lung cancer as well as gastrointestinal cancers, including stomach cancer, colorectal cancer, liver cancer and esophageal cancer.
Editor's Note: The story has been updated with additional comments from a BeiGene spokesperson on the company's regulatory plan for the Rationale 301 data.