On March 6, 2025 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on developing oncology drugs, reported the successful submission of a Phase Ib clinical trial application in Australia for CS5001 (ROR1 ADC), a key product in its 2.0 pipeline, in combination with standard-of-care therapy, in first-line diffuse large B-cell lymphoma (DLBCL) (Press release, CStone Pharmaceauticals, MAR 6, 2025, View Source [SID1234656220]). Additionally, a global, multi-center clinical trial evaluating CS5001 alone and in combination with a PD-L1 monoclonal antibody for the treatment of advanced solid tumors is also underway.

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This Phase Ib clinical trial further expands upon the previous studies of CS5001 monotherapy in patients with advanced, aggressive, and indolent lymphomas. It aims to further explore the clinical application value of CS5001 across the full spectrum of DLBCL disease and continue to expand its scope in solid tumor treatment. The trial expansion includes:

• In combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for the treatment of patients with DLBCL who have not received prior systemic therapy;

• Combination with standard therapy for patients with relapsed or refractory DLBCL;

• Monotherapy for patients with ROR1-positive advanced solid tumors;

• Combined with sugemalimab for the treatment of patients with advanced solid tumors.

Dr. Jianxin Yang, CEO, President of R&D, and Executive Director of CStone Pharmaceuticals, said, "We are very pleased to see this important progress in the clinical development of CS5001 (ROR1 ADC). Existing data have demonstrated that CS5001 exhibits broad potential in both solid tumors and lymphomas. In a Phase II clinical study, the ROR1 ADC combined with R-CHP achieved impressive complete response (CR) rates in first-line DLBCL. With the expansion of our Phase Ib clinical trial from late-line monotherapy to combination therapy in the frontline setting, CS5001 has the potential to bring groundbreaking therapeutic benefits to patients with DLBCL and reshape the standard of care for this disease. Furthermore, as the first ROR1 ADC with demonstrated clinical anti-tumor activity in both solid tumors and lymphomas, we are actively advancing the development of CS5001 in solid tumors and look forward to its subsequent clinical success."

Currently, a global, multicenter Phase Ib clinical trial of CS5001 is progressing simultaneously in the United States, Australia, and China. Enrollment is underway in the monotherapy cohort for both aggressive and indolent advanced lymphomas, with the goal of subsequently expanding into a Phase II, single-arm, registrational study. Enrollment is also expected to commence in combination with CS5001 for first-line or relapsed/refractory DLBCL, as well as in the monotherapy and combination treatment of advanced solid tumors.

About the CS5001 (ROR1 ADC)

CS5001 is an antibody-drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1). This drug utilizes a unique design, combining a tumor-specifically activated pyrrolobenzodiazepine (PBD) protoxin payload and a linker. CS5001 is internalized by tumor cells only after reaching them. Within lysosomes, the linker is cleaved by a specific enzyme highly expressed in tumor cells, releasing the PBD protoxin. The PBD protoxin is then activated within the tumor cells, leading to precise cell killing. This "dual-control" mechanism of linker plus protoxin effectively mitigates the toxicity issues associated with traditional PBD payloads and significantly extends the safety window. CS5001 has demonstrated complete tumor suppression in multiple preclinical cancer models, along with favorable serum half-life and pharmacokinetic properties, demonstrating its significant clinical development potential and broad application prospects in the treatment of various solid and hematological tumors. In addition, CS5001 uses directed coupling technology to achieve a precise drug-antibody ratio (DAR), providing strong guarantees for 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 co-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.

At the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, first-in-human data from a CS5001 study in patients with advanced solid tumors and lymphomas were presented as a poster. Subsequently, at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, updated clinical data on CS5001 as a monotherapy for advanced lymphomas were also presented.

CS5001 demonstrated a favorable safety profile and significant anti-tumor activity across 10 dose cohorts in a Phase 1a dose-escalation trial:

• At the initially selected Phase II recommended dose (RP2D) level (125 μg/kg), CS5001 achieved an objective response rate (ORR) of 70% and 100% for advanced B-cell non-Hodgkin lymphoma and Hodgkin lymphoma, respectively;

• Significant efficacy signals for CS5001 were observed in advanced solid tumors such as pancreatic cancer, ovarian cancer, non-small cell lung cancer, and triple-negative breast cancer;

• CS5001 showed good tolerability in patients with multi-line-treated advanced B-cell lymphoma and solid tumors.