Oncternal Therapeutics has dosed the first patient in the Phase I/II ONCT-534-101 study of ONCT-534 to treat metastatic castration-resistant prostate cancer (mCRPC).

The dose escalation/dose expansion, multi-centre, open-label, single-arm study is designed to assess the pharmacokinetics, tolerability, safety and anti-tumour activity of the dual-action androgen receptor inhibitor ONCT-534.

mCRPC patients who have relapsed or are refractory to androgen receptor signalling inhibitors (ARSIs) such as apalutamide, darolutamide, abiraterone and enzalutamide are included in the study.

The recommended Phase 2 dose (RP2D) will be determined in the Phase I portion and will be used in the Phase II study to further validate the dose and assess the efficacy and safety of ONCT-534.

Oncternal chief medical officer Salim Yazji said: “Preclinical studies suggest that ONCT-534 may address important tumour escape mechanisms that result in resistance to currently available AR inhibitors, such as enzalutamide or abiraterone.

“We intend to advance the dose escalation portion of the Phase I/II Study ONCT-534-101 quickly, and we will be enrolling patients in sites across the US over the coming weeks and in the United Kingdom in early 2024.

“We expect to report initial clinical data in the first half of 2024.”

ONCT-534 inhibits cell growth and induces AR degradation by interacting with both the N-terminal and the ligand-binding domains of the androgen receptor.

The company’s product portfolio also includes the autologous chimeric antigen receptor T cell therapy ONCT-808 for the treatment of several solid tumours and haematological malignancies.