Ibrilatazar (ABTL0812) autophagy inducer fails ITT PFS but trends to longer OS in ECOG 0 mPDAC

Ibrilatazar (ABTL0812) is a first-in-class oral agent designed to induce cytotoxic autophagy selectively in cancer cells; PanC-ASAP randomized first-line metastatic PDAC patients to ibrilatazar (1300mg TID) + FOLFIRINOX vs placebo + FOLFIRINOX in a Phase IIb double-blind design (n=140; NCT04431258; 23 sites across the US/Spain/France/Israel). The primary endpoint was negative in ITT (mPFS 9.4 vs 7.9 months; HR 0.95; 90% CI 0.69–1.33; p=0.814), but an exploratory subgroup suggested benefit in ECOG 0 (n=66): mPFS 11.1 vs 6.5 months (HR 0.60; p=0.089) and mOS 19.3 vs 12.0 months (HR 0.57; p=0.072)—numerically above historical first-line FOLFIRINOX benchmarks (mOS ~11.1 months; mPFS ~6.4 months), while the ITT PFS sits within the expected FOLFIRINOX range. Safety looked broadly FOLFIRINOX-like with similar grade ≥3 neutropenia (21% vs 22%) and slightly higher diarrhea (21% vs 16%); neurotoxicity was 0% vs 14% (ibrilatazar vs placebo), suggesting no obvious additive neuropathy signal on top of oxaliplatin.