RE: ESMO14 Oct 2025 07:55
Abstract is published
https://cslide.ctimeetingtech.com/esmo2025/attendee/confcal_2/presentation/list?q=Ava6000
Background
FAP-Dox (AVA6000) is a peptide drug conjugate (PDC), comprising doxorubicin (dox) bound to a peptide by a linker that is specifically cleaved by FAP, which is overexpressed in the TME of many solid tumors.
Methods
The safety, PK and preliminary efficacy of AVA6000 was studied in a first-in-human, multicenter phase I trial. AVA6000 was administered i.v. using a 3+3 design in pts with locally advanced or metastatic solid tumors categorized as high to mid range FAP (FAPhigh and FAPmid). AUC based dosing was implemented to calculate maximum number of AVA6000 cycles.
Results
Final Phase 1 data with 63 pts (median age 60 yr, range 30-79), median 2 prior therapy lines (range, 0-7) received escalating AVA6000 doses from 80 to 385 mg/m2 i.v. q3w; the starting dose was 160 mg/m2 in the q2w arm. The safety profile was favorable with frequent grade 3-4 hematologic toxicities of neutropenia (19%), leukopenia (9.5%), and lymphopenia (6.3%). Non-hematologic grade 3/4 toxicity in >2pts were limited to fatigue (n=2, 3.2%). Three pts with DLTs were observed: grade 2 cardiac failure (120 mg/m2), grade 3 febrile neutropenia (385/200 mg/m2) and grade 4 neutropenia/ thrombocytopenia (200 mg/m2) in 1 pt. No severe cardiac events were observed despite dosing up to the equivalent dox exposure associated with a lifetime max dose of 550 mg/m2. Compared to conventional dose dox, PK showed reduced systemic exposure (AUC, 5-77% reduction v. conventional dox) and peak concentration (Cmax,78-93% reduction). Concentrations of free dox in tumor were ∼2 log higher than plasma. PK modelling showed that conventional dox and released dox have different first pass effects, limiting the exposure of normal tissues to low released dox including the heart. Four PR and 5 minor responses were observed in pts with FAPhigh tumor types including salivary gland cancer and soft tissue sarcoma.
Conclusions
AVA6000 is active in FAPhigh tumors and well tolerated, delivering high concentration of free dox to the TME relative to plasma. Multiple responses were observed in patients indicating activity of the PDC. The pre|CISION PDC concentrates payload in the TME while sparing normal tissues from exposure
Sign In
Follow the stocks
