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.

The present effort to develop robust immunohistochemistry (IHC) reagents for these targets was undertaken to enable a potential diagnostic assay for our novel immuno-oncology drug candidate, ALPN-202, a conditional CD28 costimulator and dual PD-L1/CTLA-4 checkpoint inhibitor currently in a phase 1 clinical trial... Successful development of proprietary mAbs against CD28, CD80, and CD86 has been accomplished with good performance characteristics for IHC applications. Such reagents will be particularly useful in future studies to assess the prognostic relevance of these biomarkers in cancer and other diseases, and also may be incorporated in companion diagnostic strategies for patient stratification in trials of drugs involving checkpoint inhibition and/or T cell costimulation. Means, Sanderson, Peng, and Maurer disclose they are consultants for Alpine Immune Sciences.