LONDON and PHILADELPHIA — September 16, 2026
Avacta Therapeutics 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 data from the first three dose levels demonstrated a favorable safety profile, including at a dose approximately 50% higher than the maximum tolerated dose of conventional exatecan, together with pharmacokinetic findings consistent with Avacta’s preclinical modeling. The company said the clinical data provide initial evidence that AVA6103 is delivering controlled release of exatecan as designed, supporting continued dose escalation and evaluation of its next-generation pre|CISION platform in solid tumors.
FOCUS-01 Data Support Controlled Exatecan Release
The first three AVA6103 dose levels enrolled 19 patients across two parallel dosing arms administered every two weeks or every three weeks. Patients are being evaluated for safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy across selected advanced or metastatic solid tumors, including colorectal, pancreatic ductal adenocarcinoma, gastric and gastroesophageal junction, cervical and small cell lung cancers. Plasma PK data showed rapid reduction of circulating AVA6103 followed by prolonged low-level release of the pre|CISION peptide and exatecan, consistent with the controlled-release mechanism observed in preclinical studies. Avacta also reported detection of released peptide for up to 48 hours after dosing, which the company said is consistent with retention of the PDC within tumors and gradual cleavage from a proposed tumor-localized “drug reservoir.”
AVA6103 Shows Favorable Safety at Escalating Doses
Safety findings across the first three dose levels showed limited toxicity relative to historical data for conventional exatecan and comparable payload doses of Enhertu® (trastuzumab deruxtecan). AVA6103 was evaluated at 1.5 mg/m², 3 mg/m² and 4.5 mg/m², with the third dose representing approximately a 50% increase over the reported maximum tolerated dose of conventional exatecan. Avacta reported 0% neutropenia, 5% thrombocytopenia, 16% anemia and 5% nausea or vomiting among the 19 treated patients. The company also presented a preclinical head-to-head comparison with Enhertu in a HER2-positive, FAP-positive gastric cancer patient-derived xenograft model. While Enhertu slowed tumor growth, AVA6103 produced deep and prolonged partial responses in all six treated animals under the dose-dense regimen evaluated. These findings remain preclinical and are separate from the ongoing clinical efficacy assessment.
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Avacta Advances Next-Generation pre|CISION Pipeline
The FOCUS-01 program is central to Avacta’s strategy to expand the pre|CISION platform into next-generation targeted oncology medicines. The company is continuing to enroll patients into the fourth dose level across both Q2W and Q3W arms, with first clinical efficacy data for AVA6103 anticipated in the first half of 2027. Avacta expects clinical tumor biopsy data to provide additional evidence regarding tumor retention and the proposed drug-reservoir mechanism. The company also plans to present its Dual Payload Next Gen Program, including AVA6207, in the fourth quarter of 2026, while additional data from the first-generation AVA6000 program are expected later in the year. The early safety and PK findings from AVA6103 provide clinical evidence supporting the controlled-release design of the next-generation pre|CISION platform as Avacta continues to advance multiple targeted oncology programs.
Source: Avacta Therapeutics, press release
