On December 19, 2024 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer drugs, reported that the first patient has been successfully enrolled in the global multi-center Phase 1b clinical trial of CS5001 (ROR1 ADC), a key product in its 2.0 pipeline (Press release, CStone Pharmaceauticals, DEC 19, 2024, View Source [SID1234656224]).
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To date, CS5001 has demonstrated a favorable safety profile and significant anti-tumor activity across 10 dose cohorts in a Phase 1a dose-escalation trial. CS5001 has been well-tolerated in patients with multiply pretreated advanced B-cell lymphoma and solid tumors, with no dose-limiting toxicities (DLTs) observed across all 10 dose cohorts. At the initially selected Phase II recommended dose (RP2D) of 125 μg/kg, CS5001 achieved ORRs of 70% and 100% in advanced B-cell non-Hodgkin’s lymphoma and Hodgkin’s lymphoma, respectively . Furthermore, significant efficacy signals have been observed in advanced solid tumors such as non-small cell lung cancer and pancreatic cancer.
Dr. Jianxin Yang, CEO, President of R&D, and Executive Director of CStone Pharmaceuticals, said, "This year, the clinical results of CS5001 have been presented at numerous international conferences and have garnered widespread attention within the industry. The latest clinical data demonstrate that CS5001 monotherapy achieves a higher ORR than competing agents in both aggressive and indolent advanced lymphomas, and the efficacy data have stabilized with increasing patient enrollment. Therefore, we believe CS5001 has the potential for accelerated registration and marketing, as well as the potential to impact the frontline combination therapy landscape . We are very pleased to see the initiation of a Phase 1b dose optimization and expansion trial of CS5001, which is expected to be further expanded into a Phase 2, single-arm, registration-enabling trial in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) . Concurrently, we will continue to explore the safety and efficacy of CS5001 in Phase 1b, either as a monotherapy or in combination with frontline standard therapies, across a variety of hematologic malignancies and solid tumors, with the goal of bringing innovative therapies with even greater survival benefits to cancer patients worldwide."
About the CS5001 (ROR1 ADC)
CS5001 is an antibody-drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1). CS5001 features a unique design, utilizing a tumor-specifically activated pyrrolobenzodiazepine (PBD) protoxin payload and a linker. CS5001 is delivered only after tumor cell internalization. Within the lysosome, the linker is cleaved by a specific enzyme highly expressed in tumor cells, releasing the PBD protoxin, which is then activated and killed within the tumor cell. This "dual-control" mechanism of linker plus protoxin effectively mitigates the toxicity issues associated with traditional PBD payloads, resulting in a wider safety window. CS5001 has demonstrated complete tumor inhibition in several preclinical cancer models and exhibits favorable serum half-life and pharmacokinetic properties. All of this indicates that CS5001 has significant clinical development potential and broad application prospects in a variety of solid tumors and hematological malignancies. Furthermore, CS5001 utilizes directed conjugation technology to achieve a precise drug-antibody ratio (DAR), facilitating homogeneous production and large-scale production.
In October 2020, CStone Pharmaceuticals and LigaChem Biosciences, Inc. (LCB) entered into a licensing agreement for the development and commercialization of CS5001. CS5001 was originally synthesized by LCB and ABL bio, two leading Korean biotech companies. Under the terms of the agreement, CStone Pharmaceuticals obtained exclusive development and commercialization rights for CS5001 worldwide, excluding Korea.
Data from the first-in-human study of CS5001 in patients with advanced solid tumors and lymphomas were presented as a poster at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Furthermore, updated clinical data on CS5001 as a monotherapy for advanced lymphomas were recently presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.