ASCO: With Opdivo-Yervoy combo, Bristol Myers calls Roche and AstraZeneca's bets in first-line liver cancer

Following fellow immunotherapy regimens by Roche and AstraZeneca, Bristol Myers Squibb’s Opdivo and Yervoy want to carve out a piece of the first-line liver cancer market, too.

The BMS immunotherapy duo pared down the risk of death by 21% compared with either Merck and Eisai’s Lenvima or Bayer’s Nexavar in patients with previously untreated advanced hepatocellular carcinoma, according to data from the phase 3 CheckMate-9DW trial.

Specifically, patients who received Opdivo and Yervoy lived 3.1 months longer than those who got either one of the two tyrosine kinase inhibitors at the median, reaching 23.7 months. The results were shared Tuesday at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

What was unclear, though, is whether Opdivo and Yervoy’s benefit was driven by their comparison with Nexavar, because recent analyses have pointed to Lenvima as the more powerful liver cancer med between the two in the first line.

BMS' chief medical officer Samit Hirawat, M.D., in an interview with Fierce Pharma, pointed out that the trial was not designed to make comparisons between the Opdivo-Yervoy regimen and each of the two TKIs separately.  

It’s worth noting that the control group’s 20.6-month median overall survival (OS) was quite impressive. Back in 2022, Lenvima helped first-line liver cancer patients enrolled in Merck’s LEAP-002 trial live a median of 19 months, which, at the time, was the longest reported for the drug in a phase 3 trial. In that study, Merck and Eisai found the combination of Keytruda and Lenvima failed to significantly beat Lenvima monotherapy on OS. The PD-1/TKI combo’s median OS was 21.2 months.

The BMS PD-1/CTLA4 combo of Opdivo and Yervoy now looks to be on a collision course with Roche’s PD-L1/VEGF combo of Tecentriq and Avastin as well as AstraZeneca’s PD-L1/CTLA4 regimen containing Imfinzi and Imjudo. The two existing cocktails in first-line liver cancer got their FDA approvals based on data against Nexavar.

In the IMbrave150 trial, Tecentriq and Avastin originally logged a death risk reduction of 42%. But median OS at that time was not reached for the Roche regimen. A post hoc, descriptive analysis with a longer follow-up reported the combo’s median OS at 19.2 months versus 13.4 months for Nexavar.

In the HIMALAYA study, Imfinzi and Imjudo showed a median OS of 16.4 months versus 13.8 months for Nexavar. The AZ regimen’s death risk reduction was 22%.

Besides the Big Pharma players, Elevar Therapeutics and partner Jiangsu Hengrui Pharma are looking to introduce their anti-PD-1/VEGFR combo of camrelizumab and rivoceranib in first-line liver cancer. The two partners’ applications were recently rejected by the FDA because of manufacturing and clinical trial inspection problems.

In the CARES-310 study, the Elevar/Hengrui combo delivered 22.1 months of median OS versus 15.2 months for Nexavar at an interim analysis. The experimental regimen was linked to a death risk reduction of 38%. 

At the final OS analysis, the Elevar/Hengrui regimen’s median OS reached 23.8 months, although its death risk reduction fell to 36%, according to results shared at ASCO’s 2024 annual meeting.

It would be difficult to compare BMS’ latest results with the others given differences in their trial populations, follow-up time and the comparator arm.

When AZ released the HIMALAYA data in early 2022, the British pharma touted the Imfinzi-Imjudo duo’s three-year OS rate, 31%, as unprecedented.

Now, Opdivo and Yervoy have broken that record as 38% of patients who took the combo were still alive after three years, versus 24% for Nexavar, in CheckMate-9DW.

Doctors will select treatment based on the patient’s characteristics and each regimen’s own profile, Hirawat said. The Opdivo-Yervoy combo can obviously help patients who can’t tolerate Avastin, although Hirawat argued that the pure immunotherapy regimen can attract beyond those patients.

“One of the things that we’re seeing is that, as we follow these patients longer and longer, the tail end of the curve is flattening out,” Hirawat said of the survival curves seen with the Opdivo-Yervoy regimen. “So patients who benefit can benefit for a very long time.”