Phase 2/3 AMT-116 CD44v9-targeted topoisomerase I ADC vs docetaxel±ramucirumab in NSCLC.

This open-label, global, multicenter, randomized Phase 2/3 study from Multitude Therapeutics tests AMT-116, a CD44v9-directed antibody-drug conjugate that delivers a topoisomerase I inhibitor payload to CD44v9-expressing tumor cells, in advanced/metastatic non-squamous EGFR-wildtype NSCLC after progression on platinum chemotherapy and anti–PD-1/PD-L1 therapy. Phase 2 dose-finds between 4 mg/kg and 5 mg/kg given every 2 weeks, then Phase 3 compares AMT-116 against investigator’s choice: docetaxel (a microtubule inhibitor chemotherapy) alone or docetaxel plus ramucirumab (Eli Lilly’s anti-VEGFR2 monoclonal antibody). The design also allows certain actionable non-EGFR alterations (e.g., ALK) provided patients have received appropriate prior targeted therapy and platinum chemo, reflecting real-world post–chemo-immunotherapy sequencing. Today, this population commonly receives docetaxel±ramucirumab or other later-line single-agent chemotherapy, with clinical trial ADCs a key strategy to improve outcomes beyond modest response rates.