TP-3654 (PIM Inhibitor)
TP-3654 is an investigational inhibitor of PIM kinases.1
PIM as a potential target in cancer treatment
PIM kinases are frequently overexpressed in various hematologic and solid tumors, allowing cancer cells to evade apoptosis and promoting tumor growth.2
TP-3654 has shown activity in reducing the growth of bladder carcinoma cell lines in vitro.1 When delivered orally in preclinical models of bladder cancer, TP-3654 reduced tumor growth in vivo.1
Clinical trials of TP-3654 are currently being conducted in patients with advanced solid tumors or myelofibrosis.
Phase 1: First-in-human clinical trial of oral TP-3654 in patients with advanced solid tumors
A phase 1, open-label, dose-escalation, safety, PK, and PD study designed to determine the maximum tolerated dose and dose-limiting toxicities of TP-3654 in patients with advanced solid tumors.
Primary Outcome Measures
- Maximum tolerated dose
- Incidence of dose-limiting toxicities
Secondary Outcome Measures
- PK profile
- Antitumor activity
- PD effects
- Recommended phase 2 dose
Key Inclusion Criteria
- Age ≥18 years
- ECOG PS ≤2
- Life expectancy ≥3 months
- Histologically confirmed diagnosis of advanced metastatic, progressive, or unresectable solid tumor
- Refractory to, or intolerant of, established therapy
- One or more tumors measurable or evaluable as outlined by modified RECIST v1.1
See ClinicalTrials.gov (NCT03715504) for comprehensive eligibility criteria.
For sites in the US, visit ClinicalTrials.gov (NCT03715504).
PK=pharmacokinetic; PD=pharmacodynamic; ECOG PS=Eastern Cooperative Oncology Group
Performance Status; RECIST=Response Evaluation Criteria in Solid Tumors.
TP-3654 is an investigational agent and is not approved by the US FDA or any other regulatory authorities.
PIM=proviral integration site for Moloney murine leukemia virus.
- Foulks JM, Carpenter KJ, Luo B, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014;16(5):403-412. 2. Mondello P, Cuzzocrea S, and Mian M. Pim kinases in hematological malignancies: where are we now and where are we going? J Hematol Oncol. 2014;7:95.