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Astra holds its own in stage III lung cancer

Despite Imfinzi’s failure in the Pacific-2 study the AstraZeneca drug seems to be holding its own in inoperable stage III lung cancer. On Friday Bristol Myers Squibb’s challenge in this space failed when the Checkmate-73L trial, where Opdivo plus chemoradiotherapy (CRT) and Yervoy went head to head against Imfinzi and CRT, failed for PFS. Bristol said nothing about this study’s Opdivo plus CRT cohort, but since this wasn’t a consideration for the primary PFS endpoint any effect would have been irrelevant statistically given the failure of the Yervoy-containing arm. Imfinzi has long been US-approved in stage III patients who haven’t progressed on CRT, and Pacific-2 had tried to expand this to the pure front-line setting of patients who haven’t received CRT. Ironically this was also the setting of Checkmate-73L, so it can be assumed that CRT remains a sound first-line option here. Keytruda also has a label in stage III NSCLC, but this is in patients who aren’t candidates for CRT, and who express PD-L1 (Astra’s Pacific win was driven by PD-L1-positives, and the EMA restricted Imfinzi’s stage III label to these patients). Other stage III NSCLC failures include Incyte’s Zynyz and BeiGene’s Tevimbra.


Selected phase 3 trials of anti-PD-(L)1 MAbs in unresectable stage III NSCLC

PacificAstraZenecaImfinzi, vs placebo1st-line maintenance (not progressed on CRT)Approved in US, Feb 2018; approved in EU (in PD-L1 ≥1%), Sep 2018
Pacific-2AstraZenecaImfinzi + CRT, vs CRT1st-lineFailed for PFS, Nov 2023
Pacific-8AstraZenecaImfinzi + domvanalimab, vs Imfinzi1st-line maintenance (not progressed on CRT)Ends Jun 2028
Keynote-042Merck & CoKeytruda, vs chemo1st-line (not candidates for CRT), PD-L1 ≥1%*Approved in US, Apr 2019
Keylynk-012Merck & CoKeytruda + CRT +/- Lynparza, vs Imzinfi + CRT1st-lineEnds Feb 2027
Keyvibe-006Merck & CoKeytruda + vibostolimab + CRT, vs Imfinzi + CRT1st-lineEnds Sep 2028
Gemstone-301CStone/ PfizerCejemly (sugemalimab), vs placebo1st-line maintenance (not progressed on concurrent or sequential CRT)Approved in China, Jun 2022
NCT04325763Apollomics/ China TaiBenmelstobart +/- anlotinib, vs placebo1st-line maintenance (not progressed on concurrent or sequential CRT)Ended Dec 2022
Skyscraper-03RocheTecentriq + tiragolumab, vs Imfinzi1st-line maintenance (not progressed on CRT)Ends Oct 2024
Checkmate-73LBristol Myers SquibbOpdivo + CRT +/- Yervoy, vs Imfinzi + CRT1st-lineFailed for PFS, May 2024
Podium-301IncyteZynyz (retifanlimab) + CRT, vs CRTUnspecifiedTrial withdrawn
Rationale-001BeiGeneTevimbra + CRT1st-lineTrial terminated

Notes: CRT=chemoradiotherapy; *included stage IV as well as stage III. Source: OncologyPipeline.


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