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 |
Astrazeneca | |||||
Dream3R | Imfinzi +/- chemo, vs chemo | 1L | OS | PrECOG, LLC | Yet to get under way |
Roche | |||||
Beat-meso | Tecentriq + Avastin + chemo, vs Avastin + chemo | 1L | PFS & OS | European Thoracic Oncology Platform | Primary completion Oct 2024 |
Source: clinicaltrials.gov & scientific papers. |