On April 27, 2020 Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, reported the design of NEON-1, the first-in-human study of ALPN-202, a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I, in the Phase I Trials in Progress Virtual Poster Session (Press release, Alpine Immune Sciences, APR 27, 2020, View Source [SID1234556622]).
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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 Mitchell Gold, MD, Alpine’s Chairman and CEO. "ALPN-202 embodies the unique founding concepts of Alpine’s vIgD platform, incorporating tri-functional agonism and antagonism in a single proprietary functional domain. It is now positioned to determine the clinical relevance of localized CD28 costimulation to the immunotherapy of cancer. We look forward to opportunities to report upon its progress in appropriate future settings."
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.
About ALPN-202
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.