Molecular Partners AG announced it had presented the final data from its Phase 1 dose-escalation study of MP0317 at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024, held in Chicago, IL, USA. MP0317 is a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment (TME) by anchoring to fibroblast activation protein (FAP) which is expressed in high amounts around tumors. This tumor-localized approach has the potential to deliver greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

Mechanistic data & clinical response: The final analysis of this phase 1 dose-escalation study included 46 patients with advanced solid tumors and confirms earlier reported interim analysis findings. MP0317 treatment resulted in target occupancy in tumor biopsies with evidence of TME remodeling as characterized by increases in dendritic cells (DC), T follicular helper cells and plasma cells, as well as IFN? downstream activation and DC maturation gene signature score increases.

These findings were further supported by observed elevation of serum levels of CXCL10, a pro-inflammatory downstream effector of the IFN? signaling. In terms of clinical response, one patient achieved an unconfirmed partial response and stable disease was observed in 14 additional patients.

The data support further clinical evaluation of MP0317 in combination with complementary anticancer therapies. Dose-response analyses of the final trial data propose MP0317 at dosages of 1.5mg/kg or above as providing an optimal benefit-risk profile, with adjustable dosing frequency to match a combination dosing scheme. Safety & tolerability; MP0317 displayed a favorable and manageable safety profile across all nine planned dosing cohorts (0.03?10 mg/kg administered intravenously weekly (Q1W) or every 3 weeks (Q3W).

The most frequently observed adverse reactions were fatigue and lower grade infusion-related reactions (grade 1?2). Dose-limiting toxicity was reported in one patient (transient asymptomatic grade 3 elevation of liver enzymes) at the highest planned dose of 10 mg/kg administered Q3W.