Though Roche’s Tecentriq became the first ever anti-PD-(L)1 drug to be approved in perioperative lung cancer, the company has managed to lose this headstart. Merck & Co’s Keytruda trumped Tecentriq with an all-comers label in the adjuvant setting (Tecentriq’s label was limited to PD-L1 expressers), Bristol Myers Squibb’s Opdivo was first with a neoadjuvant approval, and now Opdivo threatens to add adjuvant use to its label, after the Checkmate-77T study was on Friday toplined positive for event-free survival. Keytruda presents a further threat, with success in the neoadjuvant Keynote-671 trial leading to a US filing on which the FDA is to decide by 16 October. And AstraZeneca’s Imfinzi has scored in the neoadjuvant Aegean trial, which featured at a plenary session of this year’s AACR. It is unclear whether Astra has filed these data with regulators, and Aegean is continuing to OS readout. Meanwhile, Roche’s Impower-030 trial, in a similar setting to Keynote-671 and Aegean, was initially due to yield data in 2021, but in February Roche said it was continuing to 2024, suggesting that interim analysis had failed to show a sufficiently positive effect; Impower-030’s clinicaltrials.gov entry now shows a primary completion date of January 2025. Key anti-PD-(L)1 MAb studies in perioperative NSCLC Neoadjuvant NSCLCAdjuvant NSCLCOpdivoCheckmate-816Checkmate-77T** FDA approved in stage IB-IIIA all-comers, 4 Mar 2022;Stage II-IIIBEFS 31.6mth vs 20.8mth, pCR 24% vs 2.2%Toplined positive for EFS, Sep 2023; continuing to OS assessmentKeytrudaKeynote-671*Keynote-091 (Pearls)Stage II, IIIA & resectable IIIB; filed, with 16 Oct 2023 Pdufa dateFDA approved in IB-IIIA all-comers, 27 Jan 202324mth EFS 62.4% vs 40.6%, pCR 18.1% vs 4.0%, 24mth OS 80.9% vs 77.6%DFS 58.7mth vs 34.9mth in all-comers, but not significant in ≥50% PD-L1 expressersImfinziAegean*Mermaid-1Stage IIA to "select" IIIBStage II-III; 2024 readoutEFS HR=0.68, pCR 17.2% vs 4.3%; continuing to OS assessmentTecentriqImpower-030*Impower-010Stage II, IIIA & "select IIIB"; readout delayed from 2021 to 2022 to 2024 to 2025FDA approved in PD-L1 +ve (≥1%) stage II-IIIA disease, 15 Oct 2021DFS NR vs 35.3mth in PD-L1 expressersNotes: *also has an adjuvant stage; **also has a neoadjuvant stage. EFS=event-free survival; pCR=pathological complete response; DFS=disease-free survival. Source: OncologyPipeline & company expectations of timing.
Though Roche’s Tecentriq became the first ever anti-PD-(L)1 drug to be approved in perioperative lung cancer, the company has managed to lose this headstart. Merck & Co’s Keytruda trumped Tecentriq with an all-comers label in the adjuvant setting (Tecentriq’s label was limited to PD-L1 expressers), Bristol Myers Squibb’s Opdivo was first with a neoadjuvant approval, and now Opdivo threatens to add adjuvant use to its label, after the Checkmate-77T study was on Friday toplined positive for event-free survival. Keytruda presents a further threat, with success in the neoadjuvant Keynote-671 trial leading to a US filing on which the FDA is to decide by 16 October. And AstraZeneca’s Imfinzi has scored in the neoadjuvant Aegean trial, which featured at a plenary session of this year’s AACR. It is unclear whether Astra has filed these data with regulators, and Aegean is continuing to OS readout. Meanwhile, Roche’s Impower-030 trial, in a similar setting to Keynote-671 and Aegean, was initially due to yield data in 2021, but in February Roche said it was continuing to 2024, suggesting that interim analysis had failed to show a sufficiently positive effect; Impower-030’s clinicaltrials.gov entry now shows a primary completion date of January 2025.
Key anti-PD-(L)1 MAb studies in perioperative NSCLC
| | Neoadjuvant NSCLC | Adjuvant NSCLC |
|---|
| Opdivo | Checkmate-816 | Checkmate-77T** |
FDA approved in stage IB-IIIA all-comers, 4 Mar 2022; | Stage II-IIIB |
EFS 31.6mth vs 20.8mth, pCR 24% vs 2.2% | Toplined positive for EFS, Sep 2023; continuing to OS assessment |
| Keytruda | Keynote-671* | Keynote-091 (Pearls) |
Stage II, IIIA & resectable IIIB; filed, with 16 Oct 2023 Pdufa date | FDA approved in IB-IIIA all-comers, 27 Jan 2023 |
24mth EFS 62.4% vs 40.6%, pCR 18.1% vs 4.0%, 24mth OS 80.9% vs 77.6% | DFS 58.7mth vs 34.9mth in all-comers, but not significant in ≥50% PD-L1 expressers |
| Imfinzi | Aegean* | Mermaid-1 |
Stage IIA to "select" IIIB | Stage II-III; 2024 readout |
EFS HR=0.68, pCR 17.2% vs 4.3%; continuing to OS assessment |
| Tecentriq | Impower-030* | Impower-010 |
Stage II, IIIA & "select IIIB"; readout delayed from 2021 to 2022 to 2024 to 2025 | FDA approved in PD-L1 +ve (≥1%) stage II-IIIA disease, 15 Oct 2021 |
DFS NR vs 35.3mth in PD-L1 expressers |
