Camrelizumab

Helping win the FDA's approval in first-line liver cancer, Opdivo and Yervoy significantly reduced the risk of death by 21% compared with either Lenvima or Nexavar in a late-stage trial. Bristol Myers Squibb has received the FDA’s green light to introduce another immunotherapy-based treatment in first-line liver cancer.The company’s combination of Opdivo and Yervoy is now approved for patients with newly diagnosed unresectable or metastatic hepatocellular carcinoma, the FDA said Friday.The immunotherapy regimen combines two well-established agents and may offer the potential for a longer life compared with traditional targeted therapy, Wendy Short Bartie, Bristol Myers’ senior VP of U.S. oncology commercialization, said in an interview with Fierce Pharma.The first-line approval also converted a previous accelerated approval for Opdivo-Yervoy as a second-line liver cancer treatment. Further, it puts BMS toe to toe with two other immuno-oncology regimens—Roche’s Tecentriq and Avastin, and AstraZeneca’s Imfinzi and Imjudo.All three combos got their FDA approvals based on phase 3 evidence showing that they could help patients live longer versus traditional targeted therapy. The BMS regimen is unique in that its comparator included Merck & Co. and Eisai’s Lenvima, which is considered a more powerful tyrosine kinase inhibitor in the first-line liver cancer armamentarium. According to results from the CheckMate-9DW trial, Opdivo and Yervoy significantly reduced the risk of death by 21% compared with either Lenvima or Bayer’s Nexavar. The BMS cocktail extended patients’ median survival time by 3.1 months to 23.7 months.Opdivo and Yervoy mounted that statistically significant showing despite the control arm’s 20.6 months of median overall survival notably outperforming historical data, including in phase 3 trials that got Roche and AZ their first-line liver cancer nods from the FDA in 2020 and 2022, respectively. An updated analysis from Imbrave-150 showed that Tecentriq and Avastin reduced the risk of death by 34% versus Nexavar alone, with a median overall survival of 19.2 months and 15.6 months, respectively.In the phase 3 Himalaya trial, AZ’s Imfinzi and Imjudo slashed the risk of death by 22% compared with Nexavar. The median overall survival was 16.6 months for the PD-L1/CTLA-4 combo or 13.8 months for control.The CheckMate-9DW results and increasing evidence positioning Lenvima as a more efficacious first-line liver cancer drug than Nexavar raised the question of whether Opdivo-Yervoy—or any one of the three immunotherapy regimens—can beat Lenvima head to head.CheckMate-9DW isn’t designed to answer that question. Merck tried by pairing Lenvima with Keytruda, but the phase 3 Leap-002 trial failed to show a statistically significant survival benefit for that combo against Lenvima monotherapy.BMS’ Bartie also pointed to Opdivo and Yervoy’s tumor response data. The combo triggered a 36% objective response rate in the trial, compared with 13% of patients responding to either Lenvima or Nexavar. Median duration of response was more than doubled with the combo at 30.4 months versus 12.9 months for the control, although this comparison is not included in the statistical plan of the trial.What’s more, at three years, about 38% of patients on the Opdivo-Yervoy pairing remained alive in CheckMate-9DW, versus 24% of those in the control arm.“We’ve consistently heard in market research from our customers is that they will use immunotherapy combinations when the data demonstrates that it is significantly better than [Lenvima] or [Nexavar], as an example,” Bartie said. “I think when you look at the strength of this data, particularly the overall survival rates, that is what will drive physician choice.” Besides the three Big Pharma players, Jiangsu Hengrui Pharma and its partner Elevar Therapeutics are also trying to bring their China-approved checkpoint inhibitor-based combination of camrelizumab and rivoceranib to the first-line treatment setting for liver cancer in the U.S. The FDA recently rejected the partners’ applications for the second time, again because of manufacturing issues.