Dr Hanna on the Pharmacokinetic Profile of Micvotabart Pelidotin in HNSCC

“From a safety perspective, it was encouraging to see that there were not many off-target grade 3 or higher ADC-related [effects], particularly in the dose range of 3.6 mg/kg to 5.4 mg/kg."

Glenn J. Hanna, MD, the director of the Center for Salivary and Rare Head and Neck Cancers and the director of the Center for Cancer Therapeutic Innovation (Early Drug Development Program) at Dana-Farber Cancer Institute; as well as an associate professor of medicine at Harvard Medical School, discussed preliminary safety and efficacy findings with micvotabart pelidotin (formerly PYX-201) in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Micvotabart pelidotin is a first-in-concept, extracellular-cleaving antibody-drug conjugate (ADC) designed to target the tumor extracellular matrix rather than tumor cells directly. Early findings from an ongoing phase 1 trial (NCT05720117) of the agent in patients with solid tumors demonstrated its favorable pharmacologic characteristics, including low levels of free payload in circulation and a prolonged half-life, allowing dosing every 3 weeks, Hanna began. Consistent target engagement within the tumor extracellular matrix was observed compared with normal tissue, he said. The dose-escalation portion of the study identified an active dosing range of 3.6 mg/kg to 5.4 mg/kg, with dose-dependent responses beginning at 3.6 mg/kg, he noted. Many patients enrolled in the trial received treatment at the 5.4-mg/kg dose, he added.

Approximately 9 to 10 patients with HNSCC were included among the nearly 80 patients enrolled in the trial, according to Hanna. The safety profile of micvotabart pelidotin in this subgroup has been encouraging, he emphasized. Grade 3 or higher treatment-related toxicities were uncommon in the 3.6-mg/kg-to-5.4-mg/kg dose range, and adverse effects frequently associated with other ADCs—including ocular toxicity, neuropathy, and neutropenia—were not significant concerns, he stated. Mild skin toxicities were observed but were not dose limiting, Hanna reported.

Regarding efficacy, among 6 evaluable patients in the HNSCC cohort, 2 achieved confirmed partial responses, and 1 had a confirmed complete response.