Clinical trial tests combination antibody therapy in adults with advanced cancer

CS1002 plus CS1003 (nofazinlimab) had a manageable safety profile across a broad dosing range and showed promising anti-tumor activity.

2024-02-26

(Press-News.org) 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.”

Additional information
NOTE: The information contained in this release is protected by copyright. Please include journal attribution in all coverage. A free abstract of this article will be available via the CANCER Newsroom upon online publication. For more information or to obtain a PDF of any study, please contact: Sara Henning-Stout, newsroom@wiley.com

Full Citation:
“Dual CTLA-4 and PD-1 checkpoint blockade using CS1002 and CS1003 (nofazinlimab) in patients with advanced solid tumors: A first-in-human, dose-escalation, and dose-expansion study.” Sarwan Bishnoi, Dusan Kotasek, Morteza Aghmesheh, Thomas Yau, Rasha Cosman, Amy Prawira, Maggie Moore, Stephen L. Chan, Andrew Mant, Richard Eek, Robert Zielinski, Rila Su, Zhaoxuan Pan, Yiding Ma, Fei Li, Peiqi Li, and Archie N. Tse. CANCER; Published Online: February 26, 2024 (DOI: 10.1002/cncr.35226).

URL Upon Publication: http://doi.wiley.com/10.1002/cncr.35226

About the Journal    
CANCER is a peer-reviewed publication of the American Cancer Society integrating scientific information from worldwide sources for all oncologic specialties. The objective of CANCER is to provide an interdisciplinary forum for the exchange of information among oncologic disciplines concerned with the etiology, course, and treatment of human cancer. CANCER is published on behalf of the American Cancer Society by Wiley and can be accessed online. Follow CANCER on Twitter @JournalCancer and Instagram @ACSJournalCancer, and stay up to date with the American Cancer Society Journals on LinkedIn.

About Wiley     
Wiley is a knowledge company and a global leader in research, publishing, and knowledge solutions. Dedicated to the creation and application of knowledge, Wiley serves the world’s researchers, learners, innovators, and leaders, helping them achieve their goals and solve the world's most important challenges. For more than two centuries, Wiley has been delivering on its timeless mission to unlock human potential. Visit us at Wiley.com. Follow us on Facebook, Twitter, LinkedIn and Instagram.

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