FOUR Pivotal Trials Could Redefine The First-Line Melanoma Treatment Landscape in 2025

The first-line metastatic Melanoma market is currently dominated by immune checkpoint inhibitors—BMS' Opdivo + Yervoy, Opdualag, Opdivo, and Merck/MSD's Keytruda. Other treatment options include BRAF/MEK inhibitors (for BRAF+ve pts). Currently, Opdivo + Yervoy is considered as the gold standard with an mOS of 71.9 months; however, it is associated with a high rate of Gr 3/4 TRAEs (62.6%).

BMS' Opdualag, a combination of anti-LAG-3 (relatlimab) + anti-PD-1 (nivolumab), entered the US market at the end of Q1'22. It has been positioned as a safer alternative to Opdivo + Yervoy, and a more effective option compared to anti-PD-1 monotherapies. However, it could not cross the OS benchmark set by Opdivo + Yervoy, and its efficacy in PD-L1-positive patients is not widely accepted. Nevertheless, within less than three years, Opdualag has captured 30% of the 1L Melanoma market share. With global revenue clocking close to $1B ($928 million to be precise) in 2024, Opdualag is expected to become a blockbuster in 2025.

Whether Opdualag would continue minting $1B every year after 2025 is uncertain, as the first-line melanoma landscape is poised for a pivotal year, with readouts expected from four Phase 3 trials in 2025. The upcoming data releases may reshape the competitive landscape and set new benchmarks.

To get a quick snapshot of where each regimen stands currently, we have developed a scatter plot highlighting efficacy, safety metrics, and enrollment numbers (N) from proof-of-concept and Phase 3 trials of all the key assets. To gain access to a complimentary version of this visual, please click here.

Here’s a quick rundown of the trials:

The first three regimens elicited promising proof-of-concept data, while the fourth is already approved as an IV formulation. We are all eager to see whether any of these can surpass the established safety and efficacy benchmarks. Of course, we will need overall survival data to really determine which (if any) can steal the crown.

By the end of the year, we also anticipate the list of key pivotal trials to grow, with promising results anticipated from key proof-of-concept trials, which include:

• BioAtla’s evalstotug (novel CTLA-4 agent) + anti-PD-1 reported promising results at SITC 2024, based on which the company plans initiation of a pivotal trial in 2025

• Mature results for Scancell’s SCIB1/iSCIB1+ (DNA-based cancer vaccines) + nivolumab + ipilumab will inform the next steps for selection of the asset for pivotal trial initiation

• Results from the randomized trial of BioNTech & Roche’s autogene cevumeran (mRNA vaccine) + pembrolizumab vs pembrolizumab are anticipated

• Initial data for Moderna’s mRNA-4359 (IDO/PD-L1 mRNA vaccine) + pembrolizumab from the 1L melanoma cohort are anticipated at a major medical meeting

Here are some interesting questions related to the 1L Melanoma space:

• How is the 1L melanoma landscape expected to evolve over the next five years? Which regimens have the potential to enter this space?

• Can Regeneron's LAG-3 inhibitor (fianlimab) + cemiplimab displace BMS's Opdualag?

• Are cancer vaccines finally poised to make a significant impact on the melanoma treatment paradigm?

• What are the emerging mechanisms of action (MoAs) shaping the future of melanoma treatment?

• What are the other regimens currently in pivotal trials, and when can we expect data readouts?

If you have any such questions about the developments in Melanoma and are looking for insights on the impact of these developments, reach out to us at support@oncofocus.com!

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