US approval gives Bristol its mesothelioma head-start

Friday marked an unusual coup for Bristol Myers Squibb’s Opdivo plus Yervoy combo: a US green light for front-line mesothelioma made it the first approval in 16 years for this hard-to-treat cancer. The sharp-eyed will also have noticed the unexpected breadth of the approval, which came in all-comers, even though the supporting study, Checkmate-743, clearly showed the effect to be driven by the 25% of subjects who had the non-epithelioid histology and represent a minority of mesothelioma patients. There was an impressive 56% reduction in risk of death versus chemo among non-epithelioids given the combo in the study, but those with epithelioid histology had a non-significant 15% reduction. It will be up to Bristol to make the most of the advantage, especially as its checkpoint blocker competition is nowhere to be seen. Keytruda’s indication-agnostic approvals mean that some mesothelioma patients can receive the Merck & Co drug, and indeed the Keynote-158 trial, which forms part of the basis for these, did include several with this cancer. But Keytruda recently failed the late-line Promise-meso study, and all phase III trials in this indication except Checkmate-743 have academic groups as primary sponsor.

Selected phase III studies of anti-PD-(L)1 drugs in mesothelioma
Study Design Setting Primary endpoint(s) Primary sponsor Data?
Bristol Myers Squibb
Checkmate-743 Opdivo + Yervoy, vs chemo 1L OS Bristol Myers Squibb mOS 18.1mth vs 14.1mth (p=0.002); mOS in epithelioid 18.7mth vs 16.2mth
Confirm Opdivo vs placebo ≥2L PFS & OS University of Southampton Primary completion Jul 2021
Merck & Co
IFCT-1901 Keytruda +/- chemo, vs chemo 1L PFS & OS Canadian Cancer Trials Group Primary completion Jul 2022
Promise-meso Keytruda vs chemo ≥2L PFS European Thoracic Oncology Platform Fail: HR for PFS 1.06; mOS 10.7mth vs 11.7mth
Dream3R Imfinzi +/- chemo, vs chemo 1L OS PrECOG, LLC Yet to get under way
Beat-meso Tecentriq + Avastin + chemo, vs Avastin + chemo 1L PFS & OS European Thoracic Oncology Platform Primary completion Oct 2024
Source: & scientific papers.

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