NCT03008018

Safety,Tolerability and MTD KA2507 (HDAC6 Inhibitor) in Patients With Solid Tumours

An Open Label Ascending Dose Study Evaluating the Safety/Tolerability, Pharmacokinetic and Pharmacodynamic Effects of KA2507 in Patients With Solid Tumours

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Karus Therapeutics Limited · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aim of the study is to evaluate the safety/tolerability, pharmacokinetic, and pharmaco-dynamic effects of KA2507 and establish the maximum tolerated dose (MTD). Patients with PD-L1 expressing solid tumors which have relapsed or are refractory to prior treatment will be eligible to participate in this study. Following completion of the multiple ascending dose study, the protocol may be amended to include expansion cohorts in patients with melanoma and/or other solid tumors.

Detailed description

The aim of the study is to evaluate the safety/tolerability, pharmacokinetic, and pharmaco-dynamic effects of KA2507 and establish the maximum tolerated dose (MTD). Patients with PD-L1 expressing solid tumors which have relapsed or are refractory to prior treatment will be eligible to participate in this study. Following completion of the multiple ascending dose study, the protocol may be amended to include expansion cohorts in patients with melanoma and/or other solid tumors. This is a multiple ascending dosing (MAD) study of up to 6 treatment regimens cohorts based on using a 3+3 design (up to 36 patients overall). The principal objective is to establish the maximum tolerated dose, safety, tolerability and pharmacokinetic (PK) profile in blood and urine of this HDAC6 inhibitor in patients with solid tumors and to explore effects on pharmacodynamic markers of target engagement and response to treatment. Daily/twice daily doses will be given as open label monotherapy. A review of safety and PK data will be conducted once the last patient in each cohort reaches day 28 of treatment. The review will confirm the dose to be used for the subsequent cohort. Dose escalation will be continued until the MTD is reached. Upon completion of the dose escalation phase of the study, dose expansion phases will be planned. Patients responding to treatment may elect to remain on therapy until disease progression, death or the investigator decides to stop treatment.

Conditions

• Solid Tumor, Adult

Interventions

Type	Name	Description
DRUG	KA2507	KA2507, an orally-active new chemical entity, is a potent and selective inhibitor of the HDAC6 enzyme, with potential clinical utility in the treatment of melanoma and other solid tumors. KA2507 has been shown to display potent in vitro activity in a range of cancer cell lines, including melanoma cell lines. KA2507 exerts potent in vivo efficacy in a syngeneic model of B16 melanoma. Here, the combination of the agent's direct tumor growth inhibition and metastasis suppression, coupled with its immunotherapeutic activity - demonstrated by decreased expression of STAT-3 and PD-L1 and increased expression of acetylated tubulin, gp100 and MHC Class I in tumors - have been observed.

Timeline

• Start date: 2017-08-07
• Primary completion: 2020-06-10
• Completion: 2020-06-10
• First posted: 2017-01-02
• Last updated: 2020-08-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study