First-In-Human Dose Finding Study of Venadaparib (IDX-1197), a Potent and Selective PARP Inhibitor, in Patients With...

Area of Science:

• Oncology
• Pharmacology

Background:

• Venadaparib is a novel poly (ADP-ribose) polymerase (PARP) inhibitor with high selectivity for PARP-1/2.
• It demonstrates potent PARP-trapping activity, inhibiting tumor growth in homologous recombination deficient (HRD) cancers.
• Preclinical studies showed efficacy in vitro and in vivo.

Purpose of the Study:

• To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anticancer efficacy of venadaparib monotherapy.
• To determine the recommended phase 2 dose (RP2D) in patients with advanced solid tumors.
• To assess venadaparib in patients who progressed after standard-of-care therapy.

Main Methods:

• Phase 1, dose-finding study with a 3+3 design.
• Dose escalation from 2 mg/d to 240 mg/d.
• Inclusion of patients with advanced solid tumors, including breast and ovarian cancers.

Main Results:

• No dose-limiting toxicities observed up to 240 mg/d.
• Tumor shrinkage observed at doses ≥ 40 mg/d, irrespective of BRCA mutation status.
• Recommended Phase 2 Dose (RP2D) established at 160 mg once daily, with ≥ 90% PAR inhibition at 10 mg/d.

Conclusions:

• Venadaparib demonstrated clinical benefit and was generally well-tolerated.
• Further research is needed to explore efficacy in other tumor types and combinations.
• Biomarker exploration is warranted for future venadaparib studies.