ZYNLONTA approved but label-expansion path blocked by mortality signal; survival rides on LOTIS-7 glofitamab combo reaching Phase 3

ADC Therapeutics is a commercial-stage company with an approved targeted cancer drug for aggressive B-cell lymphoma, though a label expansion is blocked by a mortality signal observed in trials.

ZYNLONTA (loncastuximab tesirine-lpyl), an antibody-drug conjugate targeting CD19 in aggressive B-cell lymphoma, carries an accelerated approval but its confirmatory LOTIS-5 filing was rejected by FDA over a threefold Grade 5 mortality imbalance. The thesis now pivots to whether ZYNLONTA plus glofitamab, showing 89.8% ORR in Phase 1b, can secure Breakthrough Therapy designation and advance to a Phase 3 that $219M in cash and runway into 2028 could support. The mortality signal in LOTIS-5 is the defining structural risk: it clouds the base approval's durability and raises the bar for any new regulatory package.