Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC

Summary

This is a First-in-Human Phase IA/IB/II open label dose escalation study of intravenous (IV) administration of ONC-392, a humanized anti-CTLA4 IgG1 monoclonal antibody, as single agent and in combination with pembrolizumab in participants with advanced or metastatic solid tumors and non-small cell lung cancers.

Timeline

Start

2020-09-16

Primary completion

2026-06-30

Completion

2027-12-31

Publications

• Background Zhang Y, Du X, Liu M, Tang F, Zhang P, Ai C, Fields JK, Sundberg EJ, Latinovic OS, Devenport M, Zheng P, Liu Y. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Res. 2019 Aug;29(8):609-627. doi: 10.1038/s41422-019-0184-1. Epub 2019 Jul 2.
• Background Du X, Tang F, Liu M, Su J, Zhang Y, Wu W, Devenport M, Lazarski CA, Zhang P, Wang X, Ye P, Wang C, Hwang E, Zhu T, Xu T, Zheng P, Liu Y. A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Cell Res. 2018 Apr;28(4):416-432. doi: 10.1038/s41422-018-0011-0. Epub 2018 Feb 22.
• Background Du X, Liu M, Su J, Zhang P, Tang F, Ye P, Devenport M, Wang X, Zhang Y, Liu Y, Zheng P. Uncoupling therapeutic from immunotherapy-related adverse effects for safer and effective anti-CTLA-4 antibodies in CTLA4 humanized mice. Cell Res. 2018 Apr;28(4):433-447. doi: 10.1038/s41422-018-0012-z. Epub 2018 Feb 20.
• Background May KF Jr, Roychowdhury S, Bhatt D, Kocak E, Bai XF, Liu JQ, Ferketich AK, Martin EW Jr, Caligiuri MA, Zheng P, Liu Y. Anti-human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a hu-PBL-SCID model: a new method for preclinical screening of costimulatory monoclonal antibodies. Blood. 2005 Feb 1;105(3):1114-20. doi: 10.1182/blood-2004-07-2561. Epub 2004 Oct 14.
• Background Lute KD, May KF Jr, Lu P, Zhang H, Kocak E, Mosinger B, Wolford C, Phillips G, Caligiuri MA, Zheng P, Liu Y. Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti-CTLA-4 antibodies. Blood. 2005 Nov 1;106(9):3127-33. doi: 10.1182/blood-2005-06-2298. Epub 2005 Jul 21.
• Background Liu Y, Zheng P. Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy. Trends Pharmacol Sci. 2020 Jan;41(1):4-12. doi: 10.1016/j.tips.2019.11.003. Epub 2019 Dec 10.
• Results Li T, Tang M, Kelly, K, Chen HA, Joo S, Khan I, Do N, Touomou R, Chen D, Liu Y, Zheng P. 949 First-in-human study of the first acid pH-sensitive and recycling CTLA-4 antibody that preserves the immune tolerance checkpoint to avoid immunotherapy-related adverse events in cancer patients. Journal for ImmunoTherapy of Cancer, 2021. 9(Suppl 2): p. A998-A998. doi: 10.1136/jitc-2021-SITC2021.949
• Results Hu-Lieskovan S, He K, Tang M, Chen D, Liu Y, Zheng P, Li T. 594 Dose escalation of next generation anti-CTLA-4 antibody ONC-392 in combination with fixed dose of pembrolizumab in patients with advanced solid tumors. Journal for ImmunoTherapy of Cancer, 2022. 10(Suppl 2): p. A622-A622. doi: 10.1136/jitc-2022-SITC2022.0594
• Results He K, Carbone DP, McKean M, Balaraman R, Shah S, Arrowsmith E, Peguero JA, Joshi R, He AR, Milillo A, Hamm JT, Goldstein MG, Li Z, Liu Y, Zheng P, Li T. Safety and clinical activity of target-preserving anti-CTLA-4 antibody ONC-392 as monotherapy in NSCLC patients who progressed on PD(L)1-targeted immunotherapy. Journal of Clinical Oncology, 2023. 41(16_suppl): p. 9024-9024. doi: 10.1200/JCO.2023.41.16_suppl.9024
• Results He K, McKean M, Balaraman R, Shah S, Arrowsmith E, Peguero JA, Hamm JT, He AR, Spira AI, Milillo-Naraine A, Joshi R, Goldstein MG, Carbone DP, Tang M, Hu-Lieskovan S, Li Z, Chen D, Chou HY, Yang J, Liu Y, Zheng P, Li T. 599 Single-agent safety and activities of target-preserving anti-CTLA-4 antibody gotistobart (ONC-392/BNT316) in PD-(L)1 resistant metastatic NSCLC and population PK analysis in patients with solid tumors. Journal for ImmunoTherapy of Cancer, 2023. 11(Suppl 1): p. A682-A682. doi: 10.1136/jitc-2023-SITC2023.0599

Drugs

Indications