Avacta Therapeutics Reports AVA6103 Phase 1 FOCUS-01 Trial Data
核心洞察
Avacta Therapeutics (搜索) reported clinical proof of mechanism for AVA6103, its pre|CISION controlled-release peptide-drug conjugate, in the Phase 1 FOCUS-01 trial in select solid tumors.
AVA6103 showed a clean safety profile through three dose levels, including a payload dose 50% above the maximum tolerated dose of conventional exatecan.
Clinical pharmacokinetic data aligned closely with preclinical modeling, with controlled exatecan release evident for days after dosing and a head-to-head preclinical comparison favoring AVA6103 over Enhertu.
Avacta Therapeutics (搜索) (AIM: AVCT) announced clinical proof of mechanism for AVA6103, its next-generation controlled-release pre|CISION peptide-drug conjugate (PDC), in the ongoing Phase 1 FOCUS-01 trial. Preliminary Phase 1a data in patients with select solid tumors showed a clean safety profile through the first three dose levels, including a payload dose level 50% higher than the maximum tolerated dose (MTD) of conventional exatecan, and clinical pharmacokinetic data that aligned closely with preclinical modeled PK, with controlled release of exatecan evident in patients for days after dosing.
The first three dose levels (1.5 mg/m2, 3 mg/m2 and 4.5 mg/m2) completed enrollment of 19 patients across two parallel arms dosed every two weeks or every three weeks. AVA6103-derived exatecan produced minimal toxicity compared with equivalent dosing of topoisomerase I inhibitors: neutropenia 0% versus 22% with similar doses of Enhertu and 64% at the conventional exatecan MTD, thrombocytopenia 5% (1/19), anemia 16% (3/19), and nausea and vomiting 5% (1/19). Screening is ongoing at dose level 4 in both arms.
In a head-to-head preclinical comparison using a HER2 (搜索)+ and FAP (搜索)+ gastric cancer (搜索) patient-derived xenograft model, AVA6103 produced deep and prolonged partial responses in 6/6 animals, while Enhertu slowed growth with 1/6 showing progression as best response. FOCUS-01 enrolls patients with locally advanced or metastatic colorectal cancer (搜索), pancreatic ductal adenocarcinoma (搜索), gastric/gastroesophageal junction cancers, cervical cancer (搜索) or small cell lung cancer (搜索). First efficacy data, including clinical tumor biopsies, are anticipated in H1 2027, with trial-in-progress presentations planned at the AACR Conference on Pancreatic Cancer and the ESMO Congress in 2026.