CStone Pharmaceuticals announced that the abstract containing the preliminary data from the first-in-human, global, multi-regional, phase 1a/1b study of CS5001 (ROR1 ADC) in patients with advanced solid tumors and lymphomas has been published on the website of the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting. Additional up-to-date clinical data will be presented in a poster session during the ASCO Meeting. Abstract Title: A phase 1a/1b, multi-regional, first-in-human study of CS5001, a novel anti-ROR1 ADC, in patients with advanced solid tumors and lymphomas.

Session date and time: June 1, 2024, from 9:00 a.m. to 12:00 p.m. (Central Daylight Time), Abstract number for publication: 3023, CS5001, one of the key assets in CStone Pipeline 2.0, is a novel ROR1-targeted ADC designed with a unique pyrrolobenzodiazepine (PBD) prodrug. This study aims to evaluate the safety, pharmacokinetics (PK), and anti-tumor activity of CS5001 in patients with advanced solid tumors and B-cell lymphomas. As of the data cut-off date in the abstract, dose-limiting toxicity (DLT) assessments for the first eight dose levels (7 to 125 µg/kg) in phase 1a have been completed without observing any DLTs and the maximum tolerated dose (MTD) has not been reached.

CS5001 appears to be well tolerated, with expected PK characteristics and preliminary anti-tumor activity observed in various solid tumors and hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma, non-small cell lung cancer (NSCLC), pancreatic cancer, etc. As the study proceeds, the upcoming ASCO poster will for the first time disclose additional efficacy and safety data of CS5001: As of the data cut-off date in poster, the dose has been escalated to dose level 9 (156 µg/kg) with no DLTs observed, and MTD has not been 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 µg/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 µg/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 µg/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 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.

Updated data will be promptly disclosed at upcoming investor meetings and academic conferences (e.g. ESMO and ASH). Phase 1b will be initiated in the near term in multiple indications for dose optimization, followed by initiation of pivotal trials by the end of 2024.