Esmo 2021 – Keytruda challenges Jemperli and adjuvant melanoma

It might not take long for Glaxosmithkline’s Jemperli to see some direct competition. This could come from Merck & Co’s Keytruda, with the Esmo conference revealing full data from Keynote-158’s cohort D in second-line MSI-high/mismatch repair-deficient endometrial cancer, the niche in which the FDA approved Jemperli this year.

The Keytruda data will soon be reviewed by the agency, which has set a March 28, 2022 action date for approval. A separate Pdufa date for Keytruda, this coming December 4, is set for adjuvant stage II melanoma, based on the Keynote-716 trial – and, as luck would have it, this too has just yielded full data at Esmo.

The stage II melanoma setting is important as current practice is effectively watchful waiting. But it could be as big again as the more advanced stage III melanoma, where the cancer has spread to the lymph nodes, in which Keytruda already carries an adjuvant label, as does its rival, Bristol Myers Squibb’s Opdivo.

At a time when perioperative uses are becoming increasingly important for immunotherapies the chance for Merck to double Keytruda’s target adjuvant melanoma market is not to be sniffed at. Whether doctors would readily take to prescribing a drug where none is given at present is a separate question, and in December the FDA will decide whether this is appropriate.

In Keynote-716 Keytruda cut risk of disease relapse by 35% versus placebo (p=0.007), a just unveiled Esmo late-breaker reveals. The full data will be presented at a presidential session on Saturday.

Adverse events will surely be a major focus of this discussion, given that watchful waiting is the current standard for stage II disease mainly because a drug brings side effects that might not be worth risking if doing nothing is good enough. Serious drug-related adverse events were seen in 16% of Keytruda versus 4% of placebo recipients, and the resulting discontinuation rates were 15% and 3% respectively.

Endometrial niche

Meanwhile, Keytruda already carries a tumour-agnostic label for second-line MSI-high/dMMR solid tumours, as well as in non-MSI-high/dMMR endometrial cancer, so the separate Keynote-158 cohort D data are a chance for Merck to consolidate its position.

The Esmo abstract cites remission rates and an adverse-event profile that are extremely similar to those cited on Jemperli’s label, as derived from that drug’s Garnet study in relapsed MSI-high/dMMR endometrial cancer. The analysis has a relatively old data cut-off of last October, so Sunday’s full presentation will clearly be the one to watch, but the data indicate what the FDA will be reviewing.

Jemperli separately secured a tumour-agnostic US approval in MSI-high/dMMR solid cancers, also on the basis of Garnet, but it looks unlikely to become a big mover, with Evaluate Pharma sellside consensus forecasting 2026 revenue of $569m across all indications.

Merck’s Esmo data will reinforce the view that Glaxo’s best bet is to take advantage of Jemperli’s status as an approved therapy and use it as the backbone for more advanced immuno-oncology combinations.