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AskGene Pharma Dosed First Patient in Phase 3, Pivotal Trial of ASKB589 in First-Line Advanced Gastric and Gastroesophageal Junction Cancers

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Camarillo, California, January 26, 2024 – AskGene Pharma Inc. announces dosing of the first patient at a participating site in China for the Phase III pivotal trial of ASKB589. ASKB589 is a CLDN18.2 targeting antibody that is being tested in combination with CAPOX and a PD-1 inhibitor. This combination therapy is intended for the first-line treatment patients with advanced, recurrent, or metastatic gastric cancer (GC) and gastroesophageal junction (GEJ) cancer in China. This study marks the first pivotal clinical trial for triple combination therapy using an anti-claudin 18.2 antibody alongside a PD-1 inhibitor and chemotherapy, for the initial treatment of G/GEJ cancer patients (NCT04632108).

Jian-Feng (Jeff) Lu, Ph.D., CEO of AskGene, commented: “We are very happy that our pivotal phase 3 program has successfully started in China with the enrollment of the first patient. The promising results of Phase 1/2 study of triple combination suggest that the combination of ASKB589, PD-1 inhibitor, and chemotherapy may be a transformative treatment option for gastric or gastroesophageal junction adenocarcinoma and support exploring the combination in patients with earlier stages of disease. The triple combination represents an innovative approach which aims to leverage the full potential of targeted therapy, immunotherapy and chemotherapies.”

The multicenter, randomized, double-blind, standard-of-care controlled Phase 3 trial (NCT06206733) has a planned enrollment of 780 patients. Patients will receive ASKB589 plus tislelizumab and CAPOX or placebo plus tislelizumab and CAPOX on day 1 of each 3-week cycle. The primary endpoint of the trial is progression free survival (PFS), with overall survival (OS), objective response rate (ORR), duration of response (DOR) and safety serving as secondary endpoints.

The latest Phase I/II clinical results presented at ASCO GI (the American Society of Clinical Oncology Gastrointestinal Cancer Symposium) in January 2024 demonstrate an encouraging anti-tumor activity and a manageable safety profile for ASKB589 combination therapy with CAPOX and a PD-1 inhibitor1. 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 (PR) and 9 (20.0%) achieved Stable Disease as the best overall tumor response per RECISTv1.1. Disease Control Rate (DCR) was 100%.

About ASKG589

ASKB589 is a second generation anti-CLDN18.2 humanized monoclonal antibody with ADCC enhancement. To support the Phase 3 pivotal trial, more than 200 patients have been enrolled into 2 Phase I/II studies, including ASKB589 monotherapy, combination with chemotherapy, and combination with PD-1 inhibitor and chemotherapy. No dose limiting toxicity (DLT) has been observed so far, with monotherapy up to 20 mg/kg, and combination therapy up to 15 mg/kg.  A maximum tolerated dose (MTD) has not yet been reached. ASKB589 is intended for treatment of G/GEJ cancer, pancreatic cancer, and additional cancer types which express CLDN18.2.

AskGene has also developed a sensitive and specific CLDN18.2 immunohistochemistry-based companion diagnostic kit, which is used to support ASKB589 Phase III program.

About AskGene Pharma

AskGene Pharma, founded in 2012 in Camarillo, California, is dedicated to the discovery and development of novel antibodies and fusion protein therapeutics.  It has established the proprietary SmartKine® cytokine prodrug platform, which significantly improves the developability of cytokines for oncology and inflammation indications.  AskGene has multiple programs in clinical and preclinical developments.  In addition to the cytokine programs, AskGene is also developing ASKB589, an anti-CLDN18.2 monoclonal antibody currently in Phase 3 for G/GEJ cancer, and ASKG712, a bifunctional molecule targeting both VGEF and ANG-2 pathways currently in phase 1 development for ophthalmology indications.

Forward-looking statement Disclaimer

This press release contains forward-looking statements that involve risks, uncertainties, and assumptions. These forward-looking statements reflect the Company’s views at the time such statements were made with respect to future events and are not a guarantee of future performance or developments. All statements other than statements of historical fact may be deemed as forward-looking, including but not limited to: any statements regarding plans, strategies and objectives for the future management of operations, including but not limited to, our clinical development and commercialization plans; predictions of any financial information; any statement of historical results that may indicate trends in our business development; statements of any expectations or beliefs regarding future events, potential markets or market size, technological developments, product lines, clinical data, results, experiments or their implications, enforceability of intellectual property rights, competitive advantage or our position in the industry; and any hypothetical statements of the items mentioned.

Reference:

1Peng Z, Shen L, He Y, et. Al. A phase Ib/II study of ASKB589 (anti-Claudin 18.2 [CLDN18.2] monoclonal antibody) combined with CAPOX and PD-1 inhibitor as first-line treatment for locally advanced, relapsed and metastatic gastric/gastro-esophageal junction (G/GEJ) adenocarcinoma. ASCO GI 2024, Abstract # 317, Poster # E17.

AskGene Presents Interim Results of ASKB589 (anti-CLDN18.2 antibody) in Combination with CAPOX and PD-1 Inhibitor at ASCO-GI 2024

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Camarillo, California, January 18, 2024 – AskGene Pharma Inc. presented encouraging clinical results for ASKB589, an anti-CLDN18.2 antibody, at the American Society of Clinical Oncology Gastrointestinal Cancer Symposium (ASCO-GI 2024) in San Francisco on January 18-20, 2024.

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. 

About AskGene Pharma

AskGene Pharma, founded in 2012 in Los Angeles, California, is dedicated to the discovery and development of novel antibodies and fusion protein therapeutics.  It has established the proprietary SmartKine® cytokine prodrug platform, which significantly improves the developability of cytokines for oncology and inflammation indications.  AskGene has multiple programs in clinical and preclinical developments.  In addition to the cytokine programs, AskGene is also developing ASKB589, an anti-CLDN18.2 monoclonal antibody currently in Phase 3 for G/GEJ cancer, and ASKG712, a bifunctional molecule targeting both VGEF and ANG-2 pathways currently in phase 1 development for ophthalmology indications.

AskGene Pharma Received Clearance to Commence Pivotal Phase III Clinical Trial in China for ASKB589

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Camarillo, California, October 16, 2023 – AskGene Pharma Inc. announces that the Center for Drug Evaluation (CDE) of the Chinese National Medicinal Product Administration (NMPA) has granted clearance for the initiation of a Phase III clinical trial to evaluate the efficacy and safety of ASKB589 (anti-CLDN18.2 monoclonal antibody) in combination with CAPOX (capecitabine and oxaliplatin) and a PD-1 inhibitor for the first-line treatment of CLDN18.2 positive, inoperable, locally advanced, recurrent or metastatic gastric and esophagogastric junction (G&GEJ) cancer in China.  The Phase III initiation marks AskGene’s entry into the first tier of pivotal clinical studies for anti-claudin 18.2 antibody targeted therapy for gastric cancer.

ASKG589 Clinical Progress

ASKB589 is a second generation anti-CLDN18.2 humanized monoclonal antibody with ADCC enhancement. To support the Phase III study, more than 200 patients have been enrolled into a number of Phase I/II studies, including ASKB589 monotherapy, combination with chemotherapy, and combination with PD-1 inhibitor and chemotherapy. No dose limiting toxicity (DLT) has been observed so far, with monotherapy up to 20 mg/kg, and combination therapy up to 15 mg/kg. Thus, a maximum tolerated dose (MTD) has not yet been reached, indicating that ASKB589 is well-tolerated.

The Phase I/II clinical results were first presented at ASCO GI (the American Society of Clinical Oncology Gastrointestinal Cancer Symposium) in January 2023, and later at IGCC (the International Gastric Cancer Congress) in June 2023. For those patients in the Phase II dose expansion study with measurable lesions, at least one post-treatment tumor assessment, medium to high CLDN18.2 expression, and treatment with 6 or 10 mg/kg ASKB589 in combination with CAPOX (capecitabine and oxaliplatin), the investigator-confirmed objective response rate (cORR) was 79.2%, and the disease control rate (DCR) was 95.8%.

In order to better identify patients who can benefit from the treatment, AskGene has also developed a CLDN18.2 immunohistochemistry-based companion diagnostic kit. With its high sensitivity and selectivity, the diagnostic kit will become an essential component of the ASKB589 Phase III program.

The approval of Phase III clinical trial is a major milestone for ASKB589 as an innovative patient-centered first-line treatment of G&GEJ cancer. The combination therapy targets both CLDN18.2 and PD-1, and could provide a more effective treatment by boosting both innate and adaptive immune responses.

Barbara Hickingbottom, J.D., M.D., Chief Medical Officer of AskGene, commented: “Claudin 18.2 has recently been validated as a new molecular target that demonstrates the potential for clinical benefit for patients with gastric and gastroesophageal cancer. Our Phase I/II clinical trial shows that ASKB589, particularly in combination with chemotherapy or PD-1 plus 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. The clearance for starting the registrational trial marks a major milestone for the clinical development ASKB589. We look forward to conducting an efficient and successful Phase III trial and advancing ASKB589 to meet the significant unmet medical needs of gastric and gastroesophageal cancer patients in China and beyond.”

About Gastric Cancer

Gastric cancer, also known as stomach cancer, is one of the most common cancers in the world, with more than 1 million new cases and 769,000 deaths each year worldwide.  It ranks fifth in incidence rate among malignant tumors and fourth in mortality.   According to data from the World Health Organization, there were approximately 480,000 new gastric cancer cases and 370,000 deaths in China in 2020, accounting for 44% and 48.6% of the global gastric cancer new cases and deaths, respectively.

About ASKB589

ASKB589 is an innovative biological drug discovered and developed by AskGene. It is a recombinant humanized monoclonal antibody targeting CLDN18.2. ASKB589 is among the top 3 most advanced therapies against this target with no marketed drugs yet. ASKB589 mediates antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) through high-affinity binding to cancer cells. Enrollment in dose escalation for ASKB589 as monotherapy and in combination with CAPOX chemotherapy was completed in 2022. Enrollment continues in expansion cohorts of first-line advanced or metastatic patients with CLDN18.2-positive G&GEJ cancers that are being treated with ASKB589 in combination with chemotherapy. In addition to G&GEJ cancers, ASKB589 is being tested in clinical trials for other CLDN18.2-positive solid tumors such as pancreatic cancer. A pivotal study of ASKB589 in the treatment of gastric cancer has received CDE approval and is under way.

About AskGene Pharma

AskGene Pharma, founded in 2012 in Los Angeles, California, is dedicated to the discovery and development of novel antibody and fusion protein therapeutics. It has established the proprietary SmartKine® cytokine prodrug platform, which significantly improves the developability of cytokines for oncology and inflammation indications. AskGene has multiple programs in clinical and preclinical developments. In addition to the first-in-class cytokine prodrug programs in clinical state, AskGene is actively advancing several programs with the potential of being best-in-class or first-in-class into late-stage or mid-stage clinical development.

Forward-looking statement Disclaimer

This website contains forward-looking statements that involve risks, uncertainties and assumptions. These forward-looking statements reflect the Company’s views at the time such statements were made with respect to future events and are not a guarantee of future performance or developments. All statements other than statements of historical fact may be deemed as forward-looking, including but not limited to: any statements regarding plans, strategies and objectives for the future management of operations, including but not limited to, our clinical development and commercialization plans; predictions of any financial information; any statement of historical results that may indicate trends in our business development; statements of any expectations or beliefs regarding future events, potential markets or market size, technological developments, product lines, clinical data, results, experiments or their implications, enforceability of intellectual property rights, competitive advantage or our position in the industry; and any hypothetical statements of the items mentioned.