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Otsuka and Cullinan chase Dizal
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Zipalertinib, an EGFR exon 20 inhibitor originated by Otsuka's Taiho subsidiary, licensed to Cullinan and then bought back by Otsuka, is headed to the FDA. The move, a shot at an accelerated approval, comes after zipalertinib met the primary ORR endpoint of its phase 1/2 Rezilient-1 study in relapsed NSCLC patients with EGFR exon 20 insertion mutations. Cullinan said zipalertinib would be filed in the second half of this year, and its shares rose 8% on Wednesday. However, the project lags Dizal's similarly acting sunvozertinib, which was filed with priority review this month, and faces a possible July FDA action date. One question is whether either zipalertinib or sunvozertinib can receive accelerated approval given that Johnson & Johnson's Rybrevant is fully approved in second-line EGFR exon 20 NSCLC. However, Rybrevant's nod is in post-chemo patients (it also has a first-line label as part of a chemo combo), and both Rezilient-1 and sunvozertinib's supporting WU-Kong1 study included some patients who had progressed on Rybrevant as well as chemo. Cullinan licensed ex-Japan zipalertinib rights in 2019, but in 2022 Otsuka bought these back, with Cullinan retaining a US profit share. A potentially confirmatory phase 3 trial, Rezilient-3, started in 2023.
A battle in second-line EGFR exon 20 insertion NSCLC
Drug | Company | Trial | Prior Rybrevant? | Data | Note |
---|---|---|---|---|---|
Rybrevant* | J&J | Chrysalis | NA | 40% ORR in 81 patients | Full approval granted after success of ph3 (1st-line) Papillon study |
Exkivity | Takeda | AP32788-15-101 | No | 28% ORR in 114 patients | Accelerated approval rescinded after failure of ph3 (1st-line) Exclaim-02 confirmatory study |
Sunvozertinib | Dizal | WU-Kong1 | Yes | 43% confirmed ORR in 107 patients, including 36% in 14 post-Rybrevant patients | Ph3 (1st-line) WU-Kong28 study under way |
Zipalertinib | Otsuka/ Cullinan | Rezilient-1 | Yes, separate exploratory cohort | Preliminary data showed 41% ORR in 39 post-chemo patients Post-Rybrevant cohort showed 40% ORR in 30 patients | Ph3 (1st-line) Rezilient-3 study under way |
Note: *anti-EGFR x cMet MAb; the rest are small-molecule EGFR inhibitors. Source: OncologyPipeline.
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