US approval gives Jemperli a treatment niche

GSK’s Jemperli has been available since 2021, but it is only now that the US FDA has given it what could be its own niche. Today’s approval, as part of a chemo combo, for first-line MSI-high/mismatch repair-deficient (dMMR) endometrial cancer, makes it the first anti-PD drug to carry this precise indication.

Until now Jemperli was approved for dMMR solid tumours as a second-line therapy, an indication it shared with Merck & Co’s Keytruda. Bristol Myers Squibb’s Opdivo, either as monotherapy or as part of a combo with Yervoy, is approved for second-line MSI-H/dMMR colorectal cancer specifically, a cancer in which Keytruda can also be given first line.

Though this is clearly positive for GSK, a big pharma group whose oncology strategy has yet to make a major impact, endometrial cancer remains a relatively small market.

Indeed, perhaps Jemperli’s biggest chance to make an impact might come from the small Perla trial in first-line NSCLC. At December’s ESMO Immuno-oncology congress Perla met its aim of showing similar ORRs for chemo combos of Jemperli and Keytruda; moreover, Jemperli numerically beat Keytruda on ORR, 46% versus 37%, and on PFS too, yielding a 30% reduction in risk of progression or death versus the Merck drug.

Though Perla was not designed to show superiority the differences were striking, yet despite this surprising result the result went by virtually unnoticed. If Jemperli can establish its credentials versus Keytruda in this way it should have a decent chance of becoming a viable backbone for GSK’s I-O drug combinations.

Investigator-assessed PFS data in Perla. Source: Dr Solange Peters & ESMO Immuno-oncology congress.

Another way in which Jemperli could make its mark could be in dMMR rectal cancer, where a study run by the Memorial Sloan Kettering Cancer Center caused a sensation at ASCO 2021.

This curative-intent trial, in which early-stage patients were given Jemperli with the aim of delaying or even eliminating radio/chemotherapy and/or surgery, showed all 14 patients treated going into complete remission. The surprising thing here was that GSK had nothing to do with this trial, and did not even press release the result.

However, subsequently the company has moved forward in this cancer type. The GSK-sponsored phase 2 Azur-1 study, a single-cohort trial in untreated stage II/III MSI-H/dMMR rectal cancer, started in April after being endorsed by a US advisory panel in February.

New approval

Jemperli’s new approval in first-line endometrial cancer is based on the phase 3 Ruby trial, where in the MSI-H/dMMR population the chemo combo cut risk of progression or death by 72% (p<0.001); median OS in these patients produced a 0.30 hazard ratio, though this was an exploratory analysis.

Interestingly, there was also an effect in all-comers, both in terms of PFS and OS. However, an exploratory analysis in mismatch repair-proficient/microsatellite-stable patients showed a confidence interval upper bound of around 1.00, suggesting that the all-comers benefit was driven by MSI-H/dMMR patients, and accordingly this is the subgroup to which approval has now been restricted.

US anti-PD-(L)1 MAb approvals in endometrial cancer and MSI-H/dMMR tumours

Note: AA=accelerated approval.