On January 18, 2024 AskGene Pharma Inc. reported encouraging clinical results for ASKB589, an anti-CLDN18.2 antibody, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancer Symposium (ASCO-GI 2024) in San Francisco on January 18-20, 2024 (Press release, AskGene Pharmaceuticals, JAN 18, 2024, View Source [SID1234639323]).
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The results were from clinical trial NCT05632939, a Phase Ib/II, two-part, dose escalation and expansion study to evaluate the safety, tolerability, and anti-tumor activities of ASKB589 in combination with chemotherapy (CAPOX) and a PD-1 inhibitor as a first-Line treatment in patients with locally advanced, relapsed and metastatic gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma. As of December 20, 2023, a total of 62 patients with positive CLDN18.2 expression were dosed Q3W with ASKB589 combined with CAPOX and PD-1 inhibitor: 9 patients received ASKB589 at 6 mg/kg (n=3) and 10 mg/kg (n=6) in the dose escalation and 53 patients at 6 mg/kg in the dose expansion. Most of the enrolled patients had moderate to high CLDN18.2 expression (83.9%) and PD-L1 CPS ³1 (59.7%).
ASKB589 was safe and tolerated at both 6 and 10 mg/kg. No dose-limiting toxicity was observed, and maximum tolerated dose (MTD) was not identified during the escalation phase of the study. Most adverse events (AEs) were of mild severity (grade 1 or 2). The most common AEs were hypoalbuminemia (77.4%), nausea (66.1%), anemia (56.5%), neutrophil count decreased (54.8%), and vomiting (51.6%). No patients discontinued the treatment due to AEs.
Among 45 CLDN18.2 moderate to high patients (determined by a validated proprietary companion diagnostic kit) with measurable disease and at least one post-treatment tumor assessment in the 6 mg/kg dose- expansion phase, 36 (80.0%) patients achieved partial response and 9 (20.0%) achieved stable disease as the best overall tumor response per RECISTv1.1. Disease control rate was 100%. As of the cutoff date, 41(77.3%) out of the 53 patients in the dose expansion group were still on treatment.
In summary, ASKB589 plus CAPOX and PD-1 inhibitor as a first-line treatment in patients with G/GEJ cancer demonstrated good safety and tolerability. Adding a PD-1 inhibitor to ASKB589 plus CAPOX in patients with moderate to high CLDN18.2 expression resulted in encouraging anti-tumor activities with deep and durable responses. Based on the interim results of this study, NMPA greenlighted the Phase 3 study of ASKB589 in combination with CAPOX and PD-1 inhibitor as a first-line treatment in CLDN18.2 moderate to high (≥40% 2+/3+ staining) patients with advanced G/GEJ cancer in China.
Jian-Feng (Jeff) Lu, Ph.D., CEO of AskGene, commented: "Claudin 18.2 has recently been validated as a new molecular target that demonstrates clinical benefit for patients with gastric and gastroesophageal cancer. Our study shows that triple combination of ASKB589, chemotherapy, and PD-1 inhibitor can be administered safely in patients and results in a very high rate of deep and durable responses, as well as a 100% disease control rate. We have initiated the registrational trial and expect to enroll the first patient soon".
Presentation Details
Title: A Phase Ib/II Study of ASKB589 (Anti-CLDN18.2 Monoclonal Antibody) in Combination with CAPOX and PD-1 Inhibitor as a First-Line Treatment of Locally Advanced, Relapsed and Metastatic G/GEJ Cancer (NCT05632939)
Principle Investigator: Dr. Lin Shen, Peking University Cancer Hospital
Presenter: Dr. Zhi Peng, Peking University Cancer Hospital
Abstract #: 317
Poster #: E17
About NCT05632939
The NCT04632108 study is a Phase Ib/II, two-part, dose escalation and expansion study to evaluate the safety, tolerability, and anti-tumor activities of ASKB589 in combination with chemotherapy (CAPOX) and a PD-1 inhibitor as a first-Line treatment in patients with locally advanced, relapsed and metastatic G/GEJ cancer. The study includes ASKB589 dose escalation (6 and 10 mg/kg) and expansion study of ASKB589 (6 mg/kg) combined with CAPOX and PD-1 inhibitor. Patients with positive CLDN18.2 expression (any tumor cell with ≥1+ membrane staining) determined by the central lab have been enrolled.
About ASKB589
ASKB589 is an innovative biological drug discovered and developed by AskGene. It is a recombinant humanized monoclonal antibody targeting CLDN 18.2. The drug mediates antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) through high-affinity binding to CLDN18.2-expressing cancer cells. ASKB589 is intended for treatment of G/GEJ cancer, pancreatic cancer, and additional cancer types which express CLDN18.2.