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
Study | Company | Design | Setting | Status |
---|---|---|---|---|
Pacific | AstraZeneca | Imfinzi, vs placebo | 1st-line maintenance (not progressed on CRT) | Approved in US, Feb 2018; approved in EU (in PD-L1 ≥1%), Sep 2018 |
Pacific-2 | AstraZeneca | Imfinzi + CRT, vs CRT | 1st-line | Failed for PFS, Nov 2023 |
Pacific-8 | AstraZeneca | Imfinzi + domvanalimab, vs Imfinzi | 1st-line maintenance (not progressed on CRT) | Ends Jun 2028 |
Keynote-042 | Merck & Co | Keytruda, vs chemo | 1st-line (not candidates for CRT), PD-L1 ≥1%* | Approved in US, Apr 2019 |
Keylynk-012 | Merck & Co | Keytruda + CRT +/- Lynparza, vs Imzinfi + CRT | 1st-line | Ends Feb 2027 |
Keyvibe-006 | Merck & Co | Keytruda + vibostolimab + CRT, vs Imfinzi + CRT | 1st-line | Ends Sep 2028 |
Gemstone-301 | CStone/ Pfizer | Cejemly (sugemalimab), vs placebo | 1st-line maintenance (not progressed on concurrent or sequential CRT) | Approved in China, Jun 2022 |
NCT04325763 | Apollomics/ China Tai | Benmelstobart +/- anlotinib, vs placebo | 1st-line maintenance (not progressed on concurrent or sequential CRT) | Ended Dec 2022 |
Skyscraper-03 | Roche | Tecentriq + tiragolumab, vs Imfinzi | 1st-line maintenance (not progressed on CRT) | Ends Oct 2024 |
Checkmate-73L | Bristol Myers Squibb | Opdivo + CRT +/- Yervoy, vs Imfinzi + CRT | 1st-line | Failed for PFS, May 2024 |
Pod1um-301 | Incyte | Zynyz (retifanlimab) + CRT, vs CRT | Unspecified | Trial withdrawn |
Rationale-001 | BeiGene | Tevimbra + CRT | 1st-line | Trial terminated |
Notes: CRT=chemoradiotherapy; *included stage IV as well as stage III. Source: OncologyPipeline.
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