davoceticept (ALPN-202)

Cardiac autopsy from one patient confirmed immune-related myocarditis, and immunosequencing revealed expansion of a single T-cell clone that was not present in the pretreatment tumor. These cases highlight the importance of understanding risk factors that may contribute to immune-related myocarditis and other severe immune-related adverse events when CD28 agonism is targeted in the context of checkpoint inhibition.NEON-2 (NCT04920383).

Davoceticept was generally well tolerated as monotherapy at intravenous doses up to 10 mg/kg. Evidence of clinical activity was observed with davoceticept monotherapy and davoceticept in combination with pembrolizumab, notably in RCC. However, two fatal cardiac events occurred with the combination of low-dose davoceticept and pembrolizumab. Future clinical investigation with davoceticept should not consider combination with programmed death-1-inhibitor anticancer mechanisms, until its safety profile is more fully elucidated.

P1, N=29, Terminated, Alpine Immune Sciences, Inc. | Trial completion date: Dec 2024 --> Feb 2023 | Active, not recruiting --> Terminated; Sponsor decision

P1, N=62, Terminated, Alpine Immune Sciences, Inc. | Trial completion date: Dec 2024 --> Feb 2023 | Active, not recruiting --> Terminated; Sponsor decision

P1, N=62, Active, not recruiting, Alpine Immune Sciences, Inc. | Recruiting --> Active, not recruiting | N=102 --> 62 | Trial primary completion date: Dec 2024 --> Dec 2022

P1, N=29, Active, not recruiting, Alpine Immune Sciences, Inc. | Recruiting --> Active, not recruiting | N=323 --> 29 | Trial primary completion date: Aug 2024 --> Dec 2022

P1, N=323, Recruiting, Alpine Immune Sciences, Inc. | Active, not recruiting --> Recruiting

The 0.1 mg/kg cohorts have been completed without DLT. Enrollment to the 0.3 mg/kg cohorts began in September 2021.

P1, N=323, Active, not recruiting, Alpine Immune Sciences, Inc. | Recruiting --> Active, not recruiting

This study is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA. Trial Registration NCT04920383

P1, N=323, Recruiting, Alpine Immune Sciences, Inc. | Not yet recruiting --> Recruiting

P1, N=323, Not yet recruiting, Alpine Immune Sciences, Inc.