TP-1287 (Oral CDK9 Inhibitor)
TP-1287 is an oral CDK9 inhibitor that has shown favorable oral bioavailability in preclinical models. TP-1287 is enzymatically cleaved, yielding the parent drug, alvocidib, a potent inhibitor of CDK9.1
TP-1287, delivered orally in preclinical models, has shown favorable activity in downregulating transcription of target genes of CDK9, such as MCL-1. The consequent downregulation of MCL-1 protein expression is correlated to tumor regression.1
The oral administration of TP-1287 may allow for chronic dosing, which may lead to a durable inhibition of CDK9.1
Phase I: First-in-human clinical trial of oral TP-1287 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 DLT of oral TP-1287 in patients with advanced solid tumors.
Primary outcome measures:
- Incidence of DLTs and treatment-emergent adverse events
- Maximum tolerated dose
Secondary outcome measures:
- Recommended phase 2 dose
- Antitumor activity
Key inclusion criteria:
- ≥18 years of age
- ECOG PS ≤2
- Life expectancy ≥ 3 months
- Histologically confirmed diagnosis of advanced metastatic or progressive 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 (NCT03604783) for comprehensive eligibility criteria.
For sites in the US, visit ClinicalTrials.gov (NCT03604783).
PK=pharmacokinetic; PD=pharmacodynamic; DLT=dose-limiting toxicity; ECOG PS= Eastern Cooperative Oncology Group Performance Status; RECIST=Response Evaluation Criteria in Solid Tumors
TP-1287 is an investigational agent not yet approved by the US FDA or any other regulatory authorities.
- Kim W, Haws H, Peterson P, et al. TP-1287, an oral prodrug of the cyclin-dependent kinase-9 inhibitor alvocidib [Abstract 5133]. Cancer Res. 2017;77(13 suppl). doi: 10.1158/1538-7445.AM2017-5133.