At the virtual 2021 annual American Society of Clinical Oncology conference (ASCO 2021) on June 4–8, results from the Phase III RELATIVITY-047 study for Bristol-Myers Squibb’s (BMS) relatlimab were presented. Previously untreated patients with advanced melanoma were randomized to receive either relatlimab monotherapy or relatlimab + Opdivo (nivolumab), with progression-free survival (PFS) assessed by independent review as the primary endpoint.

At a median follow-up of 13.2 months, PFS was 10.12 months versus 4.63 months for Opdivo monotherapy at a hazard ratio (HR) of 0.75. This difference is likely driven by the LAG-3 positive (≥1%) subgroup, as patients who expressed <1% LAG-3 had a much lower PFS of 4.83 months for the combination. Adverse events were similar between arms, with 40.3% of patients experiencing grade 3/4 events in the combination versus 33.4% in the monotherapy arm. Also, the addition of relatlimab to Opdivo led to an increase of only 5.4% in treatment discontinuation. Overall survival (OS) and overall response rate remain blinded and will be followed up in the future.

The current standard of care for this patient population is BMS’ Opdivo + Yervoy (ipilimumab). In the Checkmate-067 study, Yervoy + Opdivo showed a PFS of 11.5 months, and a very impressive median OS of 72.1 months, albeit at a much longer follow up of 6.5 years. While the PFS results are comparable and the safety profile of relatlimab + Opdivo is more favorable than that of Yervoy + Opdivo, GlobalData expects that few physicians will be comfortable with using relatlimab up front without robust evidence of OS improvement. Key opinion leaders interviewed by GlobalData have overall favorable opinions of relatlimab and believe its tolerability can be key for clinical adoption, but they are still skeptical of its efficacy.

The field for immunotherapies that can promote response to or reverse resistance to immune checkpoint inhibitors (ICIs) is highly desirable and that market will be worth billions of dollars upon identification of the most promising agents. The RELATIVITY-047 trial is the first late-stage trial globally to demonstrate efficacy of a combination of anti-LAG-3/PD-1 agents.  BMS is expected to file a biologics license application for relatlimab with the FDA by the end of 2021, making FDA approval in 2022 possible. Unless relatlimab demonstrates a key improvement over Yervoy + Opdivo, GlobalData projects its sales to reach only $66M in melanoma globally by 2029. However, other indications less responsive to Yervoy + Opdivo, such as colorectal cancer, may well prove to be more lucrative for relatlimab.