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Another Zynlonta shift?

Very preliminary results of ADC Therapeutics’ underwhelming marketed drug Zynlonta were enough for the group to secure $105m in a stock and warrant offering this week, but whether they stand up to scrutiny – let alone prompt yet another development shift – is anyone’s guess. The data came from 15 patients with relapsed marginal zone lymphoma (MZL), and the headline 87% complete remission rate (plus a further patient with partial response) seems highly impressive. Still, this came from an investigator-sponsored trial at just two centres, and excluded 35 subjects who were as yet not evaluable. MZL is a relatively indolent cancer, raising questions about clinical need – especially as two patients discontinued because of Zynlonta-associated toxicity. In 2017 Imbruvica became the first drug specifically indicated for MZL, but its accelerated US approval was rescinded when the confirmatory Selene study failed to show a survival benefit. Brukinsa also has accelerated approval for MZL, and on a cross-trial basis the Zynlonta data look favourable. The question for ADC now is whether to embark on formal MZL development, especially after scrapping earlier Zynlonta trials in other indolent lymphomas.


Cross-trial comparisons in marginal zone lymphoma

DrugMechanismCompanyStatus in MZLTrialNORRCR rate
ImbruvicaBTK inhibitorAbbVie/J&J2017 AA for post-CD20 use; rescinded 2023PCYC-11216346%3%
BrukinsaBTK inhibitorBeiGene2021 AA for post-CD20 useNCT038464276656%20%
ZynlontaAnti-CD19 ADCADC TherapeuticsNot approvedNCT05296070*15**93%87%

Notes: AA=accelerated approval; *investigator-sponsored; **trial enrolled 50 patients. Source: prescribing info & company statement.


Molecular Drug Targets