Temab-A (ABBV-400) monotherapy hits 63% ORR in heavily pre-treated EGFR-mutant NSCLC— similar to triple combo benchmark

Temab-A is a c-Met–targeting antibody–drug conjugate armed with a novel topoisomerase-1 inhibitor. In the phase 1 dose-expansion cohort (NCT05029882), 41 EGFR-mutated, advanced non-squamous NSCLC patients who had progressed after TKIs and platinum chemo (median 3 prior lines; 32% baseline brain mets) received 2.4–3.0 mg/kg IV Q3W. About one-third of NSCLC patients harbor an EGFR mutation. Confirmed ORR reached 63% (26/41) with tumor shrinkage in every evaluable patient and 83% clinical benefit. 54% of responses were ongoing ≥6 months at the 9.7-month cutoff. Grade ≥3 AEs were primarily hematologic (anemia 27%, neutropenia 22%). Interstitial-lung disease/pneumonitis occurred in 7% (grade ≥3 = 2%). 20% of patients discontinued treatment due to TRAEs, including 1 treatment-related death. By contrast, the bispecific mAb (EGFR and MET) amivantamab-vmjw in combination with carboplatin and pemetrexed is the preferred regimen for patients with nonsquamous histology and EGFR mutations, based on the MARIPOSA-2 trial, which demonstrated a median progression-free survival (PFS) of 6.3 months, an objective response rate (ORR) of 64%, and a discontinuation for toxicity of 27% for the combination.