On January 24, 2023 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 2023) in San Francisco on January 19-21, 2023 (Press release, AskGene Pharmaceuticals, JAN 24, 2023, View Source [SID1234626531]).
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The results were from clinical trial NCT04632108, a Phase I/II, two-part, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of ASKB589 monotherapy (Part A) and in combination with chemotherapy (Part B) in patients with advanced solid tumors. In Part A, patients with heavily pre-treated solid tumors received ASKB589 at doses ranging between 0.3 and 20 mg/kg every 3 weeks (Q3W). In Part B, doses of ASKB589 ranging from 3 to 15 mg/kg were given in combination with chemotherapy Q3W. The majority of the enrolled patients had gastric or gastroesophageal junction (G/GEJ) cancer (77.5% for Part A; 91.1% for Part B).
As of January 04, 2023, a total of 85 patients were treated with ASKB589 (40 patients received monotherapy and 45 patients received ASKB589 in combination with capecitabine and oxaliplatin (CAPOX)). The highest dose of monotherapy tested was 20 mg/kg, and the highest dose of ASKB589 in combination with chemotherapy was 15 mg/kg. ASKB589 was safe and well tolerated both as monotherapy and in combination with chemotherapy. No dose-limiting toxicity was observed during the escalation phase of the study in Part A or Part B. A maximum tolerated dose (MTD) was therefore not identified for either monotherapy or combination therapy. The majority of adverse events were of mild severity (grade 1 or 2). The most common adverse events were gastrointestinal related events, including nausea (50% for monotherapy; 64.4% for combination therapy) and vomiting (45% for monotherapy and 73.3% for combination therapy), which were generally resolved within one week.
Among the 21 patients with CLDN 18.2-positive G/GEJ cancer who received ≥ 10 mg/kg ASKB589 monotherapy, two (2) patients had partial response (PR). One of these patients has continued in PR at 35 weeks. Among the 24 patients with CLDN 18.2-positive G/GEJ cancer who received ≥ 6 mg/kg ASKB589 combined with CAPOX chemotherapy as first-line treatment for metastatic or unresectable advanced disease, the objective response rate (ORR) was 75% (18 PR patients), and the disease control rate (DCR) was 100%.
In summary, ASKB589 was well-tolerated with manageable safety and good tolerability both as monotherapy and in combination with chemotherapy. ASKB589 combined with CAPOX regimen as first-line treatment for patients with CLDN 18.2-positive gastric or gastroesophageal junction cancer showed deep and durable antitumor activity at dose levels ≥ 6 mg/kg.
Barbara Hickingbottom, J.D., M.D., Chief Medical Officer of AskGene, commented: "Claudin 18.2 has recently been validated as the first new molecular target that demonstrates the potential for clinical benefit for patients with gastric and gastroesophageal cancer in quite some time. This clinical trial shows that ASKB589, particularly in combination with chemotherapy, can be administered safely in patients with these types of cancer and results in a high rate of deep and durable responses, as well as a remarkable disease control rate. We are planning to initiate a registrational trial in claudin 18.2 selected G/GEJ patients in 2023. "
Presentation Details
Title: Safety and Anti-Tumor Activity of a Phase I/II Study of ASKB589, an Anti-Claudin 18.2 (CLDN18.2) Monoclonal Antibody as a Monotherapy and in Combination with Chemotherapy in Patients with Solid Tumors
First Author: Miao Zhang, Peking University Cancer Hospital
Presenter: Barbara Hickingbottom, AskGene
Abstract #: 397
Poster #: G19
About NCT04632108
The NCT04632108 study is a first-in-human study evaluating the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of ASKB589 monotherapy and combination chemotherapy in patients with advanced solid tumors. The study includes ASKB589 monotherapy dose escalation and expansion study (Part A) and dose escalation and expansion study of ASKB589 combined with chemotherapy (Part B). The patients in the dose escalation studies were enrolled regardless of the expression of CLDN18.2, while only the patients who test positive for CLDN18.2 by the central lab have been enrolled in the dose expansion study.
About ASKB589
ASKB589 is an innovative biological drug discovered and developed by AskGene. It is a recombinant humanized monoclonal antibody targeting claudin 18.2. The drug mediates antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) through high-affinity binding to cancer cells. ASKB589 is intended for use in gastric and gastroesophageal junction cancers and pancreatic cancers. The multi-center Phase I/II clinical trial in China is led by Professor Shen Lin from Peking University Cancer Hospital.