633P - First-in-human dose-escalation study of basroparib (STP1002) in patients with advanced-stage solid tumors

Background

The pathogenesis of colorectal cancers is largely driven by mutations of the tumor suppressor gene APC that lead to aberrant activation of the β-catenin–dependent (canonical) Wnt signaling pathway. Basroparib (STP1002) is a tankyrase inhibitor targeting the Wnt/β-catenin signaling pathway and has demonstrated potent activity against TNKS1 and TNKS2 with high selectivity for PARP in vitro.

Methods

This is a phase 1, open-label, multicenter study (NCT04505839) to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of Basroparib (STP1002) in patients (pts) with advanced solid tumors. The primary objectives were safety and tolerability. Key secondary endpoints included PK and Best Overall Response. A dose escalation determined the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). STP1002 was given PO until disease progression, intolerance, or withdrawal of consent.

Results

25 patients were treated in dose escalation. 13 patients were female with a median age of 54.0 years. Most common tumor types included colorectal cancer (23 pts) and renal cell carcinoma (2 pts). Treatment Related Adverse Events (TRAE) were reported in 12 patients. TRAEs were mostly low grade (21 events were Grade 1-2) and rarely led to treatment discontinuation. Three TRAEs at Grade 4 were reported. No Grade 5 TRAEs were reported. The most common TRAEs were fatigue in 7 patients and nausea 3 patients. No dose limiting toxicities were detected. Best overall response of stable disease (SD) by RECIST 1.1 was observed in 4 patients, with duration of up to 2.5 months. 360 mg was determined to be the MTD and RP2D.

Conclusions

In this dose escalation study, Basroparib (STP1002) was shown to be a safe and well-tolerated TNKS1 and TNKS2 inhibitor with preliminary anti-tumor activity warranting further investigation.

Clinical trial identification

NCT04505839.

Editorial acknowledgement

Legal entity responsible for the study

ST Pharm Co.

Funding

ST Pharm Co.

Disclosure

K.P. Kim, M.J. Sung, U. Kim, X. Meng: Financial Interests, Personal, Full or part-time Employment: ST Pharm Co. All other authors have declared no conflicts of interest.