CStone Pharmaceuticals announce that a poster presentation of data from the first-in-human, global, multi-center, phase 1a/1b study of CS5001 (ROR1 ADC), one of the key assets in CStone Pipeline 2.0, in patients with advanced solid tumors and lymphomas has been made at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Key Highlights The latest first-in-human study data show that CS5001 is well tolerated with promising anti-tumor activity at various dose levels in heavily pretreated, advanced solid tumors and lymphomas. CS5001 is the first known ROR1 antibody-drug conjugate (ADC) to demonstrate clinical anti-tumor activity in both solid tumors and lymphomas.

Dose escalation in the global, multi-center, phase 1 trial of CS5001 is ongoing in the United States, Australia, and China, with plans to initiate dose-expansion studies in multiple tumor types soon and potential registrational trials in 2024. Additional up-to-date clinical data of CS5001 will be regularly disclosed at upcoming investor meetings or academic conferences, such as ESMO and ASH. CS5001 is a novel ROR1-targeted ADC designed with a unique pyrrolobenzodiazepine (PBD) prodrug.

This first-in-human study aims to evaluate the safety, pharmacokinetics (PK), and anti-tumor activity of CS5001 in patients with advanced solid tumors and B-cell lymphomas. The latest efficacy and safety data for CS5001 disclosed in the ASCO poster are as follows: As of the data cut-off date for the poster, dose-limiting toxicity (DLT) evaluation for the first nine dose levels (7 to 156 g/kg) in Phase 1a has been completed. No DLTs were observed, and the maximum tolerated dose (MTD) was not reached.

Most treatment-related adverse events observed were Grade 1 or 2 (per NCI-CTCAE v5.0), indicating that CS5001 was well tolerated by heavily pretreated patients with advanced solid tumors and lymphomas. PK data suggested dose-proportional exposure of CS5001, with similar exposure for ADC and total antibody, demonstrating excellent stability of CS5001 ADC in circulation. Encouraging anti-tumor activity has been observed in various solid tumors (per RECIST v1.1) and hematologic malignancies (per Lugano 2014): Hodgkin Lymphoma: Objective responses were observed from dose level 5 (50 g/kg) and above, including 1 complete response (CR) and 4 partial responses (PR) among 9 evaluable patients at dose levels 5-9, achieving an objective response rate (ORR) of 55.6%.

DLBCL: Objective responses were observed from dose level 7 (100 g/kg) and above, including 1 CR and 2 PRs among 6 evaluable patients at dose levels 7-9, achieving an ORR of 50.0%. In solid tumors, multiple PRs and stable diseases (SDs) with reduced tumor burden were emerging from dose level 7 (100 g/kg) and above, notably in NSCLC (1 PR and 3 SDs), pancreatic cancer (1 PR), triple-negative breast cancer (TNBC; 1 SD), and ovarian cancer (1 SD). Based on the efficacy trends observed, more potent anti-tumor activity is expected in patients with solid tumors as the dose increases.

To date, the phase 1a dose escalation in the reported study remains ongoing, with parallel backfilling of additional patients at selected higher doses to determine preliminary phase 2 recommended dose (RP2D) and to evaluate the relationship between ROR1 expression and efficacy. Phase 1b will be initiated in the near term in multiple indications for dose optimization, followed by initiation of potential pivotal trials by the end of 2024.