Daiichi Sankyo has entered a research collaboration to assess its investigational antibody drug conjugate (ADC) DS-8201 in combination with Bristol-Myers Squibb’s (BMS) Opdivo (nivolumab) in a Phase Ib clinical trial to treat HER2-expressing metastatic breast and urothelial (bladder) cancers.
Developed using ADC technology, DS-8201 features a humanised HER2 antibody attached through a tetrapeptide linker to a new topoisomerase I inhibitor (DXd) payload.
After its release into the cell, the smart chemotherapy is intended to destroy cancer cells and minimise systemic exposure to the cytotoxic payload.
Designed to leverage the body’s immune system to restore anti-tumour immune response, Opdivo is an immune checkpoint inhibitor of programmed death-1 (PD-1).
Estimated to begin enrolment in the US and Europe in the first quarter of next year, the multicentre, open-label trial will include a dose escalation part and a dose expansion part.
Daiichi Sankyo oncology research and development executive vice-president and global head Antoine Yver said: “We are excited to evaluate if the combination of these two mechanisms of action - the ability of an anti-PD-1 to harness the immune system and the potential of DS-8201 to deliver chemotherapy directly to target cancer cells - may be able to improve the outcomes of patients with HER2-expressing advanced breast and bladder cancer.”
The trial’s dose escalation part will focus on the determination of a possible recommended dose of DS-8201, to be given in combination with Opdivo to HER2-expressing breast cancer patients who are refractory to conventional therapies or who do not have a standard therapy.
During the dose expansion part, the efficacy, safety and tolerability of the combination at the determined dose level will be investigated in HER2-expressing advanced / metastatic breast cancer patients and in previously chemotherapy-treated subjects with HER2-expressing urothelial cancer.