The overall survival win came from the phase 3 CheckMate-9DW trial. BMS said it’ll evaluate the data in full and share the results with the scientific community and drug regulators.
The front-line CheckMate-9DW study serves as the confirmatory trial for Opdivo and Yervoy’s accelerated approval in the second-line, post-Nexavar setting, which was granted by the FDA in 2020.
If the FDA eventually gives the combo its go-ahead in the first-line setting, the Opdivo-Yervoy regimen will compete with Roche’s and AstraZeneca’s PD-L1 regimens. Besides those two companies, other immunotherapy players are eyeing the same field.
The positive first-line readout comes nearly three years after BMS, under pressure from the FDA, voluntarily pulled Opdivo monotherapy as a post-Nexavar liver cancer treatment from the U.S. market. The decision followed Opdivo’s failure as a first-line treatment in the CheckMate-459 trial. Data released in 2019 showed that Opdivo alone only reduced the risk of death by a nonstatistically significant 15% versus Nexavar.
Since that trial flop, Roche’s Tecentriq and Avastin in 2020 became the first immunotherapy-based treatment to be approved in previously untreated advanced liver cancer. In the IMbrave150 study, the Tecentriq-Avastin regimen slashed the risk of death by 42% versus Nexavar. In Roche’s most recent quarterly report, first-line liver cancer was cited as one of the two main growth drivers for Tecentriq.
AstraZeneca joined the first-line club in 2022 with its dual immunotherapy combo Imfinzi and Imjudo. In the phase 3 HIMALAYA trial, the AZ combo cut the risk of death by 22% against Nexavar, as the British pharma touted a 30.7% three-year survival rate for its regimen. With first-line approvals in liver cancer and non-small cell lung cancer, Imjudo collected $218 million in sales last year.
But the competitive picture isn’t complete just yet. Elevar Therapeutics and Hengrui Pharma’s applications for their China-approved combination of the VEGFR inhibitor rivoceranib (also known as apatinib) and the PD-1 inhibitor camrelizumab in first-line liver cancer are awaiting an FDA decision expected in May. During an interim analysis of an international phase 3 study coded CARES-310, rivoceranib and camrelizumab significantly cut the risk of death by 38% versus Nexavar.
And last year, Roche reported what some analysts viewed as very encouraging phase 1/2 data for its triple combination of Tecentriq, Avastin and the TIGIT inhibitorTIGIT inhibitor tiragolumab in first-line liver cancer. Roche in September advanced that triplet regimen into a phase 3 study called SKYSCRAPER-14, or IMbrave152.
Meanwhile, Merck in 2022 surprisingly found that its combination of Keytruda and Lenvima couldn’t top Lenvima alone at extending patients’ lives in first-line liver cancer. The New Jersey pharma is also exploring the possibility of adding its anti-TIGIT candidate vibostolimab to Keytruda in phase 2.