Esmo 2021 – poziotinib could add first-line string to its bow

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Spectrum’s poziotinib keeps throwing up surprises. Its multi-cohort Zenith20 lung cancer study had whiffed twice and yielded one surprising hit, on the basis of which the group plans a US filing this year. But a late-breaking Esmo abstract just made public suggests that the project could have broader potential: cohort 4, in first-line NSCLC patients whose cancer harbours Her2 exon 20 insertion, is also positive. The stated 44% confirmed remission rate in 48 subjects appears comfortably to hit Spectrum’s success criteria, and there are another two responses as yet unconfirmed. Twice-daily dosing in cohort 4 continues, but the Esmo data relate to once-daily, the same dose that Spectrum will take to the FDA in a filing focused on relapsed Her2 exon 20 insertion NSCLC. As for competition, Takeda’s now approved Exkivity (mobocertinib) and Cullinan’s CLN-081 have put up impressive results in EGFR exon 20 insertions, the niche where poziotinib failed, but little data exist on exon 20 insertions in Her2. How significant could the latter opportunity be? The sellside once expected poziotinib to sell over $500m by 2024, according to Evaluate Pharma, but now its 2026 consensus is $285m. The late-breaking data will be presented in full on Saturday.

Poziotinib's Zenith20 study in NSCLC (possibly registrational cohorts)
Cohort Setting Subjects Confirmed ORR mDOR Result
1 Relapsed, EGFR exon 20 insertions 115 14.8% 7.4mth Fail: missed undisclosed threshold
2 Relapsed, Her2 exon 20 insertions 90 27.8% 5.1mth Success: lower bound of CI >17%
3 1st-line EGFR exon 20 insertions 70 27.8% 6.5mth Fail: lower bound of CI <20%
4 1st-line Her2 exon 20 insertions 70 43.8%* 5.4mth Apparent success
6 EGFR Tagrisso failures 30  
7 Atypical EGFR or Her mutations 30  
Source: Spectrum & Esmo. Note: *data from 48 evaluable subjects, with a further 2 CRs taking unconfirmed ORR to 48%; ORR=overall remission rate; mDOR=median duration of response; CI=confidence interval.

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