Alpine Immune Sciences Presents Design of the ALPN-202 Phase 1 Study (NEON-1) at AACR Virtual Annual Meeting I
- NEON-1 is now open for enrollment for patients with advanced malignancies -
Many patients treated with checkpoint inhibitors fail to achieve an objective or complete anti-tumor response. This could be due to a lack of sufficient T cell costimluation in the tumor microenvironment, such as inadequate CD28 ligands. To address this, ALPN-202 was designed to inhibit both the PD-L1 and CTLA-4 checkpoints, while also providing a CD28 costimulatory signal. Importantly, ALPN-202’s costimulatory function is designed to depend upon PD-L1, to help ensure clinical safety and tolerability.
NEON-1 includes two parts: dose escalation and expansion cohort(s). It will enroll adults with advanced solid tumors or lymphoma refractory or resistant to standard therapy, including checkpoint inhibitors when indicated. Measurable disease is required for most participants, as are an ECOG status of 0 to 2 and adequate hematological, renal, and hepatic function. Dose escalation begins with single-participant cohorts to minimize the number of participants anticipated to receive subtherapeutic doses, followed by standard 3 + 3 cohorts where two dose regimens, weekly versus every three weeks, will be studied in parallel. Expansion cohorts will explore specific tumor types and/or biomarker-selected tumors, based upon the experience during dose escalation. Safety endpoints include dose-limiting toxicities, adverse events, and circulating cytokines. Objective responses will be assessed by RECIST v1.1 for solid tumors and Lugano criteria for lymphoma. Pharmacokinetics and pharmacodynamics will also be evaluated.
“We are particularly pleased to see ALPN-202 enter the clinic,” said
AACR has made the 2020 virtual Annual Meeting presentations freely available. Alpine’s recorded oral presentation of the NEON-1 trial design can be accessed here.
ALPN-202 is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor with the potential to improve upon the efficacy of combined checkpoint inhibition while limiting significant toxicities. Preclinical studies of ALPN-202 have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. A phase 1 trial of ALPN-202 in advanced malignancies (NEON-1, NCT04186637) is open for enrollment.
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