Avacta is stepping up development of its peptide-drug conjugate (PDC), kicking off expansion cohorts in multiple tumor types after seeing one partial response in 10 salivary gland cancer patients.
The salivary gland data come from a phase 1a trial that tested the PDC AVA6000 in patients with various FAP-positive solid tumors. AVA6000 consists of a chemotherapy drug, doxorubicin, bound to a linker that is cleaved by FAP. Because FAP is overexpressed in some tumor microenvironments, the linker may keep doxorubicin bound up until it reaches cancer cells, minimizing systemic toxicity and maximizing efficacy.
FAP expression is particularly high in salivary gland cancer. Ten people with the tumor type received 250 mg/m2 or more of AVA6000 in the phase 1a trial. One patient had a partial response—their tumor shrank by 45%—and another four people had minor reductions of 10% to 19.5%.
Avacta saw the partial response after 12 weeks in a 79-year-old man. The patient has stopped taking the study drug because he reached the maximum lifetime exposure to doxorubicin, Avacta said, but his response to treatment is ongoing. The patient began taking AVA6000 in October 2023 having progressed on another therapy.
Avacta is yet to reach the maximum tolerated dose. The biotech said AVA6000 has been well tolerated, regardless of whether it is administered every two or three weeks. Avacta reported reduced hematologic and cardiac toxicities compared to conventional doxorubicin dosed at 75 mg/m2 every three weeks.
The biotech has opened phase 1b expansion cohorts in triple negative breast cancer, soft tissue sarcoma and salivary gland cancer in the first- and second-line settings. All three indications are among the tumor types with the highest levels of FAP expression. Avacta is now screening patients and expects to treat the first people in the expansion cohorts imminently in the U.S.
There is an unmet need in salivary gland cancer, with Avacta noting the lack of a standard of care for people with distant metastasis and a five-year survival rate of 43%, but the condition is relatively rare. Success in triple negative breast cancer would move Avacta into a larger indication.