Bristol Myers Squibb presented a subgroup analysis from the RELATIVITY-047 trial for the newly approved OPDUALAG for the unresectable or metastatic melanoma patients (Abstract # 9505).
Nivolumab Mechanism of Action: Antibody-dependent cell cytotoxicity; CD223 antigen inhibitors; Programmed cell death-1 receptor antagonists; T lymphocyte stimulants
Recently, FDA approved Opdualag, a fixed-dose combination of nivolumab and relatlimab for patients with previously untreated melanoma that cannot be removed surgically or has spread (metastasized) within the body. The Opdualag FDA approval was based on results from a large Phase II/III clinical trial (RELATIVITY-047). The clinical trial results have shown that Opdualag can double the time patients with previously untreated advanced melanoma can live without disease progression compared to Opdivo alone (the current SoC) without any added safety concerns.
Further Exploratory analyses by pre-specified subgroups from the RELATIVITY-047 trial were performed for PFS, OS, and ORR. As of the data cut-off date of October 2021 and media follow up of 19.3 months, OS, PFS and ORR continued to favour the combination of nivolumab + relatlimab over nivolumab across all key subgroups.
The combination drug has shown superior pFS in key subgroups such as high tumor burden (HR:0.7), metastatic M1c stage (HR:0.83), LDH>ULN (2*ULN/ ≤ 2*ULN) (HR: 0.73-0.77), ECOG 0-1 (HR:~0.80). Unstratified HR for OS in each of the aforementioned were as follows: 0.75; 0.78; 0-76-0.93; 069-0.96 favoring nivolumab + relatilimab over nivolumab monotherapy. These results were consistent on ORR and supported nivolumab + relatlimab over nivolumab.
“Nivolumab plus relatlimab had a manageable safety profile, with no new or unexpected safety signals. These data further validate nivolumab plus relatlimab as a potential new treatment option in patients with advanced melanoma and support the benefit of dual checkpoint inhibition.”–Expert Opinion.
In March, Bristol Myers Squibb made history by introducing the first LAG-3 drug as part of an Opdivo combo called Opdualag as a treatment for patients with unresectable or metastatic melanoma. BMS’s plan to overcome the patent protection losses of Opdivo has succeeded as the clinical trial results have shown that Opdualag can double the time patients with previously untreated advanced melanoma can live without disease progression compared with Opdivo alone.
Now BMS is planning to further delve into its landmark victory by presenting data on key subgroups (including those with poorer prognoses) to back its use in various melanoma patients. These results can further help BMS gain a positive perception from the KOL’s, establishing Opdualag as a new standard of care as first-line therapy in melanoma and enhancing its market size.
First-line melanoma is just the first step BMS has planned for Opdualag. The Phase III RELATIVITY-098 trial assesses the Opdivo-plus-relatlimab cocktail versus Opdivo alone in the post-surgery treatment of stages III–IV melanoma in the adjuvant setting. The company will soon launch a registrational study for the new combo in second-line colorectal cancer. The combination of nivolumab + relatlimab was favoured over nivolumab alone across key subgroups for PFS, OS, and ORR, and findings appeared consistent with outcomes in the overall population.