On April 12, 2022 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune and inflammatory diseases, reported the oral presentation of results from the dose-escalation portion of NEON-1 (NCT04186637), a first-in-human, dose-escalation and expansion study of davoceticept monotherapy in participants with advanced malignancies, at the 2022 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Alpine Immune Sciences, APR 12, 2022, View Source [SID1234612049]).
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Highlights from the presentation include:
Despite a highly heterogeneous, heavily pretreated, advanced solid tumor population – the majority classically considered to be unresponsive to immunotherapy – 11 (23%) of 48 evaluable participants demonstrated tumor volume reduction; 26 (54%) achieved clinical benefit as defined as a best response of stable disease or better; Three (6%) remained on treatment beyond 6 months. Two partial responses were observed in colorectal and renal cell carcinoma.
Davoceticept was well-tolerated with no reported events of cytokine release syndrome. Adverse events of interest included immune-related adverse events and infusion-related reactions, the majority of which were grades 1-2. A single dose-limiting toxicity of gastritis was observed at 3 mg/kg, but a maximum tolerated dose was not reached.
Immunophenotyping demonstrated favorable increases in activated and central memory T cells, as well as reductions in regulatory T cells. Overall, pharmacodynamic analyses suggest 1 or 3 mg/kg every 3 weeks as the optimal biological dose.
Monotherapy expansion cohorts in metastatic cutaneous melanoma, renal cell carcinoma, and PD-L1-positive tumors are planned.
"These results indicate that it is indeed feasible to engage CD28 for cancer immunotherapy, and further suggest that this approach may be clinically advantageous, even for heavily pretreated cancers," remarked Stanford Peng, MD PhD, Alpine’s President and Head of Research and Development. "We eagerly look forward to advancing to expansion cohorts as soon as possible."
A copy of the oral presentation slides is available on the Scientific Publications page of Alpine’s website.
About NEON-1
NEON-1 is a first-in-human dose escalation and expansion study of davoceticept monotherapy in advanced malignancies. Dose escalation enrolled adults with advanced solid tumors refractory or resistant to standard therapy, exploring 0.001-10 mg/kg every 1 and/or 3 weeks. Expansion cohorts are planned to include cutaneous melanoma, renal cell carcinoma, or PD-L1-positive tumors at 1 or 3 mg/kg every 3 weeks. Preliminary results were previously reported at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. More information is available at www.clinicaltrials.gov (NCT04186637).
About Davoceticept (ALPN-202)
Davoceticept (ALPN-202) is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor intended for the treatment of cancer. Preclinical studies of davoceticept have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. NEON-1 (NCT04186637), a Phase 1 monotherapy dose escalation and expansion trial in advanced malignancies, was initiated in June 2020 and is progressing to expansion cohorts. NEON-2 (NCT04920383), a combination study of davoceticept (ALPN-202) and pembrolizumab was initiated in June 2021 and is currently on partial clinical hold.