Phase II/III Trial of PRL3-Zumab in Advanced Solid Tumor Patients

Summary

This is a Multi-Center, Phase II/III, open-label, single dose level (6 mg/kg) basket trial of PRL3-zumab monotherapy in solid cancer patients. The study will consist of a Screening Period (Day - 14 to Day -1) for completion of all screening assessments before the first administration of study treatment, a Treatment Period during which visits will occur every 2-week (PK T1/2 = 12 days ±2 days), once the decision to discontinue treatment for any reason, an End of Treatment (EOT) visit will be performed within 14 days ±4 days after last dose of study treatment. Safety Follow-up/EOS visit will be performed 28 days ±2 days after last dose of study treatment and survival follow-up call will be performed every month up to 6 months after EOS visit. PRL3-zumab will be administered by intravenous (i.v.) infusion till patient meets discontinuation criteria (progressive disease, clinically or per iRECIST, intolerable toxicity or withdrawal of consent). One cycle of treatment will be 4-weeks (2 infusions, 12 days±2 days apart). Patients will undergo safety assessment including laboratory tests prior to each infusion. Efficacy will be assessed by iRECIST at baseline and every 4 doses after study treatment. QoL assessments will be performed at Screening and every 4 doses ±7 days during treatment. A patient will be discontinued from study treatment if the patient progress clinically or per iRECIST criteria, or for intolerable toxicity, or if the patient withdraws consent. An EOT visit will be performed within14 days ±4 days after last study treatment dose.

Timeline

Start

2023-01-09

Primary completion

2026-12

Completion

2026-12

Publications

• Background Park DJ, Thura M, Chiu VK, Vicuna B, Ang KH, Sanchez B, Chia PL, Kuan KY, Li J, Zhang K, Zheng WH, Hsien Ng MC, Zeng Q. The PRL3-zumab paradigm: A multicenter, single-dose-level phase 2 basket clinical trial design of an unconventional cancer immunotherapy. Cell Rep Med. 2025 May 20;6(5):102120. doi: 10.1016/j.xcrm.2025.102120. Epub 2025 May 8.
• Background Loh AHP, Thura M, Gupta A, Tan SH, Kuan KKY, Ang KH, Merchant K, Chang KTE, Yon HY, Chen Y, Cheng MHW, Mahadev A, Ng MCH, Seng MS, Iyer P, Chia PL, Soh SY, Zeng Q. Exploiting frequent and specific expression of PRL3 in pediatric solid tumors for first-in-child use of PRL3-zumab humanized antibody. Mol Ther Oncolytics. 2023 Aug 18;30:153-166. doi: 10.1016/j.omto.2023.08.006. eCollection 2023 Sep 21.
• Background Chee CE, Ooi M, Lee SC, Sundar R, Heong V, Yong WP, Ng CH, Wong A, Lim JSJ, Tan DSP, Soo R, Tan JTC, Yang S, Thura M, Al-Aidaroos AQ, Chng WJ, Zeng Q, Goh BC. A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies. Target Oncol. 2023 May;18(3):391-402. doi: 10.1007/s11523-023-00962-w. Epub 2023 Apr 15.
• Background Thura M, Ye Z, Al-Aidaroos AQ, Xiong Q, Ong JY, Gupta A, Li J, Guo K, Ang KH, Zeng Q. PRL3 induces polypoid giant cancer cells eliminated by PRL3-zumab to reduce tumor relapse. Commun Biol. 2021 Jul 29;4(1):923. doi: 10.1038/s42003-021-02449-8.
• Background Thura M, Al-Aidaroos AQ, Gupta A, Chee CE, Lee SC, Hui KM, Li J, Guan YK, Yong WP, So J, Chng WJ, Ng CH, Zhou J, Wang LZ, Yuen JSP, Ho HSS, Yi SM, Chiong E, Choo SP, Ngeow J, Ng MCH, Chua C, Yeo ESA, Tan IBH, Sng JXE, Tan NYZ, Thiery JP, Goh BC, Zeng Q. PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein. Nat Commun. 2019 Jun 6;10(1):2484. doi: 10.1038/s41467-019-10127-x.
• Background Thura M, Al-Aidaroos AQO, Yong WP, Kono K, Gupta A, Lin YB, Mimura K, Thiery JP, Goh BC, Tan P, Soo R, Hong CW, Wang L, Lin SJ, Chen E, Rha SY, Chung HC, Li J, Nandi S, Yuen HF, Zhang SD, Guan YK, So J, Zeng Q. PRL3-zumab, a first-in-class humanized antibody for cancer therapy. JCI Insight. 2016 Jun 16;1(9):e87607. doi: 10.1172/jci.insight.87607.
• Background Guo K, Li J, Tang JP, Tan CP, Hong CW, Al-Aidaroos AQ, Varghese L, Huang C, Zeng Q. Targeting intracellular oncoproteins with antibody therapy or vaccination. Sci Transl Med. 2011 Sep 7;3(99):99ra85. doi: 10.1126/scitranslmed.3002296.

Drugs

Indications