Abstract OT1-02-01: 4CAST: A Phase 1b dose exploration and dose expansion, open-label study evaluating the safety and efficacy of INO-464 in combination with Chemotherapy in patients with metASTatic breast cancer
Authors: Dear Rachel F. , Batty Kathleen , Perez Beatriz , Chaffer Christine 
Published: March 2023

Abstract: Trials in progress Authors: Dr Rachel Dear, A/Prof Christine Chaffer, Dr Beatriz Perez San Juan Title: 4CAST: A Phase 1b dose exploration and dose expansion, open-label study evaluating the safety and efficacy of INO-464 in combination with Chemotherapy in patients with metASTatic breast cancer. Problem statement: Metastatic triple negative breast cancer (mTNBC) has poor outcomes, with rapid progression and a median overall survival of 16 months. Standard treatment includes chemotherapy, with a possible role for immunotherapy. The antibody-drug conjugate sacituzumab govitecan was been granted recent approval. The development of new targeted treatments remains an unmet need. The androgen receptor is a mediator of chemotherapy-resistance in triple-negative breast cancer. Taxane and platinum-based chemotherapy induces cell plasticity and the emergence of chemotherapy-resistance. The androgen receptor (AR) antagonist, INO-464, but not abiraterone or enzalutamide, blocks chemotherapy induced cell plasticity to inhibit and primary and metastatic tumour growth. Three early-phase prospective clinical studies investigating anti-androgen therapy have demonstrated clinical benefit of single-agent AR-targeted agents in women with metastatic AR positive TNBC. The 450 mg daily start dose of INO-464 was well-tolerated and declared the recommended phase 2 dose. Preliminary laboratory data demonstrates an increase in survival and suppression of metastatic TNBC when INO-464 is used in combination with docetaxel. Methods: To determine the feasibility, safety and efficacy of INO-464 in combination with chemotherapy for the treatment of metastatic breast cancer. In Part 1 (dose exploration) of the trial we aim to establish the tolerability and safety and determine the recommended phase 2 dose of INO-464 when used in combination with docetaxel. Part 1 will recruit 6-18 females or males with locally advanced or metastatic breast cancer ie hormone receptor positive, HER2-positive or triple-negative breast cancer. In Part 2 (dose expansion) the clinical activity INO-464 and docetaxel in participants with metastatic triple negative breast cancer will be assessed. Results: Ethics approval for Part 1 of the trial was granted in May 2021. The trial received governance approval from St Vincent’s Hospital governance in June 2022. Recruitment commenced on the 1 July 2022. The trial has received 40 enquiries, of which three patients were eligible and one patient has consented to the trial and will be ready to start in the next two weeks. Conclusion: This investigator-initiated trial is an example of a collaborative effort between the Garvan Institute of Medical Research and the Kinghorn Cancer Centre at St Vincent’s Hospital. If the combination of INO-464 and docetaxel is shown to be safe we look forward to recruiting to the part 2 dose expansion phase across multiple Australian sites. This is study is registered with ClinicalTrials.gov NCT04947189. Disclosure of interests: A/Prof Christine Chaffer is the Managing Director of Kembi Therapeutics that is providing the investigational product for the clinical trial.

Citation Format: Rachel F. Dear, Kathleen Batty, Beatriz Perez, Christine Chaffer. 4CAST: A Phase 1b dose exploration and dose expansion, open-label study evaluating the safety and efficacy of INO-464 in combination with Chemotherapy in patients with metASTatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-02-01.