Tumor-localized CD40 agonism with MP0317, a FAP x CD40 DARPin, reprograms the tumor microenvironment in patients with advanced solid tumors: an open-label, nonrandomized, dose-escalation phase 1 study - Report - MDSpire
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Tumor-localized CD40 agonism with MP0317, a FAP x CD40 DARPin, reprograms the tumor microenvironment in patients with advanced solid tumors: an open-label, nonrandomized, dose-escalation phase 1 study
Clinical Report: Targeted CD40 Activation with MP0317 Modifies Tumor Microenvironment
Overview
The phase 1 study of MP0317, a FAP x CD40 DARPin, demonstrated a favorable safety profile and potential antitumor activity in patients with advanced solid tumors. Notably, the treatment did not reach a maximum tolerated dose and showed promising immune modulation within the tumor microenvironment.
Background
CD40 activation is crucial for bridging innate and adaptive immunity, making it a significant target for cancer therapy. Traditional systemic CD40 agonists have faced challenges due to dose-limiting toxicities and rapid drug clearance. MP0317 offers a localized approach to CD40 activation, potentially enhancing therapeutic efficacy while minimizing systemic side effects.
MP0317 is a bispecific DARPin designed to activate CD40 specifically in the tumor microenvironment.
The study included 61 patients with advanced solid tumors, demonstrating a favorable safety profile.
No maximum tolerated dose was reached, indicating a potentially broader therapeutic window.
Most treatment-related adverse events were grade 1-2, with only one case of grade 3 transaminase elevation.
Antitumor activity included a 2% unconfirmed partial response and a 33% disease control rate at the first assessment.
Biopsies showed TME reprogramming with increased APC influx and DC maturation.
Clinical Implications
The findings suggest that MP0317 could be a promising option for patients with advanced solid tumors, particularly due to its localized mechanism of action that may reduce systemic toxicity. Clinicians should consider the potential for combination therapies to enhance the efficacy of CD40 agonism.
Conclusion
MP0317 represents a novel approach to CD40 activation with a favorable safety profile and early signs of efficacy in advanced solid tumors. Further studies are warranted to explore its full therapeutic potential.
by Neeltje Steeghs, Carlos Gomez-Roca, Iphigénie Korakis, Eelke Gort, Hilde De Winter, Nina Stojcheva, Vaia Stavropoulou, Jennifer Krieg, Paul Baverel, Elena Fernandez, Ana Maria Florescu, Lea Hoenig, Michael Peter Sanderson, Vladimir Kirkin, Philippe Legenne, Philippe Alexandre Cassier
