Clinical trial tests combination antibody therapy in adults with advanced cancer

In an early phase clinical trial, a combination of antibody-based medications targeting the immune system generated promising safety data and anti-tumor activity in individuals with various types of advanced cancer. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

Both medications tested in the trial support immune responses against tumor 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 multicenter, 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 3 mg/kg once every 3 weeks, or 3 mg/kg once every 9 weeks) were evaluated with 200 mg CS1003 once every 3 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 diarrhea, 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 tumors experienced a positive response. Higher response rates occurred with conventional and high-dose CS1002 regimens (1 mg/kg once every 3 weeks or 3 mg/kg once every 9 weeks) compared with low-dose CS1002 (0.3 mg/kg once every 3 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. “This supports further assessment of CS1002 in combination with CS1003 for the treatment of solid tumors.”

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