AACR 2022: Davoceticept (ALPN-202) Monotherapy Reduces Tumors, Supports Multiple Expansion Cohorts
- In dose escalation across a range of dose regimens, tumor volume reduction was observed in 23% of evaluable participants despite heavily pretreated, advanced solid malignancies -
- Monotherapy expansion cohorts with multiple tumor types are planned -
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
A copy of the oral presentation slides is available on the
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
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
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