ADC slides on latest Zynlonta update

ADC Therapeutics hopes to expand its CD19-directed ADC Zynlonta into earlier DLBCL lines, but the latest update from the phase 1 Lotis-7 trial sent the group's stock down 14% on Wednesday. Efficacy is deteriorating, doubts about durability are creeping in, and there were two deaths, including one deemed treatment-related.

The data come from a combination of Zynlonta plus Roche’s CD20-targeting T-cell engager Columvi in second-line-plus DLBCL. The latest overall response rate is 90% among 49 evaluable patients – versus 94% among 18 patients a year ago.

The complete response rate was 78%, which ADC claims represents an improvement over Columvi monotherapy, which produced a CR rate of 59% in the troubled second-line Starglo trial. However, Lotis-7 measured investigator-assessed best response – which likely includes unconfirmed responses, including those that might never be confirmed.

And doubts about durability are emerging. The latest update required patients to have at least six months of follow-up, and five complete responders were no longer in complete response at the cutoff date of 17 November. ADC stressed that only two of these patients had progressed, while two died while in complete response, and one was censored.

Treatment-related death

One of the deaths, due to sepsis, was deemed not treatment-related, but the other, from oedema, was. At the previous update, at EHA in June, no treatment-emergent deaths were reported.

ADC was vague about future plans with the Columvi combo, saying it would complete enrolment of around 100 patients at the selected 150µg/kg dose in the first half of 2026, and share full data later that year – then “assess regulatory and compendia strategies”. The group added that if it went down the compendia route it would only capture “a proportion” of a potential $500-800m market.

The company is also testing Zynlonta plus Ritxuan in the problematic phase 3 Lotis-5 study, with data due in the first half of 2026. Zynlonta already has FDA accelerated approval for third-line DLBCL, and Lotis-5 is a potential confirmatory trial.

The evolving Lotis-7 dataset with Zynlonta + Columvi

Notes: *12/13 pts remained in CR at data cutoff; **25/26 pts remained in CR at data cutoff; ***33/38 pts remained in CR at data cutoff. Source: company presentations.