Another cervical cancer win for Keytruda
To the extent that cervical cancer remains a significant market, given the successes of screening campaigns and HPV vaccination, Merck & Co’s Keytruda is building itself a sizeable lead while others founder. Today Astrazeneca’s Imfinzi fell by the wayside as the phase 3 Calla study, combining it with chemoradiation in front-line disease, failed to show a progression-free survival benefit against chemoradiation alone. In recent months two other competitors have suffered major setbacks: Sanofi/Regeneron pulled a US filing for Libtayo in second-line use, after Agenus did the same for balstilimab. The latter was down to the unviability of uncontrolled data backing an approval once Keytruda secured a formal first and second-line label, while the former was probably a result of insufficient data on Libtayo’s effect in patients who were not PD-L1-positive. Notably the FDA had restricted Keytruda’s label to ≥1% PD-L1 expressers, even though the Keynote-826 study had shown an effect in all-comers. Libtayo’s benefit in all-comers in the Empower-Cervical-1 trial was driven by ≥1% PD-L1 expressers, but researchers had obtained PD-L1 data from less than half of enrolees. The next keenly awaited dataset concerns Roche’s combo of Tecentriq plus the anti-Tigit Mab tiragolumab.
|Selected cervical cancer trials|
|Merck & Co||Keynote-826||1st-line||Keytruda + chemo +/- Avastin, vs chemo +/- Avastin||Positive for OS in all-comers & PD-L1+ves||Backed full US approval 1st-line (PD-L1+ves) & 2nd-line|
|Seagen||InnovaTV-204||2nd-line||Tivdak (uncontrolled)||24% ORR||Backed accelerated US approval|
|Agenus||NCT03495882||2nd-line||Balstilimab (uncontrolled)||14% ORR||US filing withdrawn 2 mths before Pdufa date|
|Regeneron/ Sanofi||Empower-Cervical-1||2nd-line||Libtayo vs chemo||Positive for OS in all-comers||US filing withdrawn 2 days before Pdufa date|
|Iovance||NCT03108495||2nd-line||Lifileucel +/- Keytruda (uncontrolled)||44% ORR (57% for combo)||Filing delayed, pending FDA discussions|
|Astrazeneca||Calla||1st-line||Imfinzi + CRT vs CRT||Failed for PFS||–|
|Roche||Skyscraper-04||2nd-line||Tecentriq + tiragolumab, vs Tecentriq||ORR||Data due H2 2022|
|Pfizer/Merck KGaA||[email protected] Cervical 017||2nd-line||Bintrafusp alfa (uncontrolled)||ORR||Ends Apr 2022|
|[email protected] Cervical 046||1st-line||Bintrafusp alfa + Avastin or various chemos (uncontrolled)||Safety||Ends May 2022|
|Source: company presentations & clinicaltrials.gov.|
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