In an early phase clinical trial, a combination of antibody-based medications targeting the immune system generated promising safety data and anti-tumour activity in individuals with various types of advanced cancer. The findings appear online in CANCER, a peer-reviewed journal of the American Cancer Society.
Both medications tested in the trial are checkpoint inhibitors, and support immune responses against tumour cells. CS1002 increases the activation and proliferation of T immune cells by binding to a T cell receptor called CTLA-4. CS1003, also called nofazinlimab, blocks the programmed cell death protein 1 that is expressed on various types of immune cells and plays a role in suppressing the immune system.
In this first-in-human multicentre, open-label study conducted from April 26, 2018 to January 18, 2022 at 9 study sites in Australia and China, phase Ia involved monotherapy dose-escalation (Part 1), which was followed by phase Ib combination therapy dose escalation (Part 2) and expansion (Part 3). Various dosing schedules of CS1002 (0.3, 1, or 3mg/kg once every three weeks, or 3mg/kg once every 9 weeks) were evaluated with 200mg CS1003 once every three weeks.
Parts 1, 2, and 3 of the trial included 13, 18, and 61 patients, respectively, who had advanced/metastatic solid, relapsed, or refractory tumors. During treatment, investigators did not observe any dose-limiting toxicities or a maximum tolerated dose. Treatment-related side effects such as diarrhoea, fatigue, and rash were reported in 30.8%, 83.3%, and 75.0% of patients in Parts 1, 2, and 3, respectively. Serious side effects such as intestinal inflammation and severe skin reactions were experienced by 15.4%, 50.0%, and 18.3% of patients in each part.
Of 61 patients evaluable for treatment efficacy, 23 (37.7%) with different types of tumours experienced a positive response. Higher response rates occurred with conventional and high-dose CS1002 regimens (1mg/kg once every three weeks or 3mg/kg once every 9 weeks) compared with low-dose CS1002 (0.3mg/kg once every three weeks) in certain cancers such as melanoma and skin cancer.
“CS1002 in combination with CS1003 had manageable safety profile across a broad dosing range and showed promising anti-tumor activities across CS1002 dose levels when combined with CS1003,” the investigators wrote. They concluded that this warranted more testing of CS1002 in combination with CS1003 for the treatment of solid tumours.
Source: Wiley
