ZL-1211 / ZAI Lab - LARVOL DELTA

Claudin18.2 as a Promising Therapeutic Target in Gastric Cancer. (PubMed, Cells) - "This narrative review presents the characterization and role of claudin 18.2 (CLDN18.2) as a promising biomarker in GC and a target for clinical therapies, more specifically CLDN18.2-targeted drugs and therapies including mABs (e.g., Zolbetuximab, Osemitamab, ZL-1211), bsAB, and CAR-T cell-based immunotherapies. We also summarize numerous ongoing worldwide clinical trials that are evaluating CLDN18.2 as a target for GC treatment. What seems to be crucial is that preclinical and clinical data indicate their high efficacy and safety."

Biomarker • IO biomarker • Journal • Review • Gastric Cancer • Oncology • Solid Tumor • CLDN18

A Study of ZL-1211 in Patients With Advanced Solid Tumor (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Zai Biopharmaceutical (Suzhou) Co., Ltd. | Phase classification: P1/2 ➔ P1

Metastases • Phase classification • Oncology • Solid Tumor • CLDN18

A Study of ZL-1211 in Patients With Advanced Solid Tumor (clinicaltrials.gov) - P1/2 | N=34 | Completed | Sponsor: Zai Biopharmaceutical (Suzhou) Co., Ltd. | Recruiting ➔ Completed | N=162 ➔ 34 | Trial completion date: Oct 2024 ➔ Apr 2024

Enrollment change • Trial completion • Trial completion date • Oncology • Solid Tumor • CLDN18

A Study of ZL-1211 in Patients With Advanced Solid Tumor (clinicaltrials.gov) - P1/2 | N=162 | Recruiting | Sponsor: Zai Biopharmaceutical (Suzhou) Co., Ltd.

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • CLDN18

Preliminary results of a phase 1/2, first-in-human, open-label, dose escalation study of ZL-1211 (anti-Claudin 18.2 mAb) in patients with unresectable or metastatic solid tumors. (ASCO 2023) - P1/2 | "ZL-1211 displayed an acceptable safety/tolerability profile to date and demonstrated preliminary antitumor effects. Clinical trial information: NCT05065710."

Clinical • Metastases • P1/2 data • Anemia • Biliary Cancer • Cholangiocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Hepatology • Leukopenia • Oncology • Pain • Pancreatic Cancer • Solid Tumor • CLDN18

Zai Lab to Highlight New Data from its Oncology Pipeline at 2023 ASCO Annual Meeting (GlobeNewswire) - P1/2 | N=162 | NCT05065710 | Sponsor:Zai Biopharmaceutical (Suzhou) Co., Ltd. | "Zai Lab Limited...will present three poster presentations with new data, including preliminary results from a clinical study evaluating its internal oncology research and development program ZL-1211, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting....Among the 10 evaluable patients included in the data analysis, the results showed ZL-1211 demonstrated a tolerable safety profile and preliminary antitumor effects. For example: There were no dose limiting toxicities (DLTs) as of the data cut-off date. The most common treatment-related adverse events (TRAEs) were gastrointestinal (GI) disorders, including nausea, vomiting, and abdominal pain. Six patients achieved stable disease with three patients having some evidence of tumor regression."

P1/2 data • Oncology • Solid Tumor

Clinical translation of biomarkers for ZL-1211, an anti-CLDN18.2 antibody, in patients with advanced solid tumors from a phase I dose-escalation study (AACR 2023) - P1/2 | "Taken together, analytical approaches developed and validated from preclinical studies were successfully translated to characterize clinical samples in the current Phase 1 trial. The exploratory analysis indicated the clinical relevance of multiple biomarkers and their potential as predictive biomarkers of ZL-1211."

Biomarker • Clinical • Metastases • P1 data • Oncology • Solid Tumor • CD8 • CLDN18 • FCGR3A

Zai Lab to Highlight New Data from its Oncology Portfolio at 2023 AACR Annual Meeting (Yahoo Finance) - "Zai Lab Limited...will present new data including a translational and biomarker data analysis from its internal oncology discovery program ZL-1211 at the upcoming 2023 American Association for Cancer Research (AACR) Annual Meeting in Orlando on April 14-19, 2023....This presentation will feature results generated from clinical patient samples using these assays to support the mechanism of action for ZL-1211.Several potential predictive biomarkers from preclinical in vitro and in vivo analyses will be highlighted in the presentation....In addition, Zai will be presenting a second poster presentation about tebotelimab, a PD-1/LAG-3 bispecific antibody."

Biomarker • Trial status • Melanoma • Mucosal Melanoma • Oncology • Skin Cancer • Solid Tumor

ZL-1211 Exhibits Robust Antitumor Activity by Enhancing ADCC and Activating NK Cell-mediated Inflammation in CLDN18.2-High and -Low Expressing Gastric Cancer Models. (PubMed, Cancer Res Commun) - P1/2 | "ZL-1211, anti-CLDN18.2 therapeutic antibody can target CLDN18.2-high as well as -low gastric cancers that may not be eligible for treatment with clinical benchmark. ZL-1211 treatment induces NK-cell activation with robust inflammation to further activate antitumor immunity in tumor microenvironment."

Journal • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18 • IFNG • IL6 • TNFA

Anti-CLDN18.2 antibody ZL-1211 enhances anti-tumor activities in combination with chemotherapy in gastric cancer models (SITC 2022) - P1/2 | "Chemotherapy, such as gemcitabine, increased CLDN18.2 mRNA and protein expression levels in cancer cells and sensitized tumor cells to ZL-1211-mediated ADCC. Furthermore, ZL-1211 in combination with SoC chemotherapies, oxaliplatin + capecitabine (CAPOX), enhanced anti-tumor efficacy in SNU601 gastric cancer xenograft model...Conclusions These data provide rationale to combine ZL-1211 with SoC chemotherapy in gastric cancer. Currently, a phase I dose escalation study is underway to assess the safety, tolerability, pharmacodynamics, and pharmacokinetics of ZL-1211 in patients with advanced solid tumors ( NCT05065710 )."

Combination therapy • Preclinical • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18

ZL-1211 exhibits robust anti-tumor activity by enhancing ADCC and activating innate and adaptive immunity in CLDN18.2-high and -low expressing gastric cancer models (AACR 2022) - P1/2 | "Taken together, our data suggest that ZL-1211 more effectively targets CLDN18.2-high gastric cancers as well as -low expressing malignancies that are not eligible for treatment with the leading clinical benchmark by inducing a robust ADCC response and activating innate and adaptive immunity to enhance anti-tumor efficacy. Clinical activity of ZL-1211 is currently under evaluation in a Phase I clinical trial (NCT05065710)."

Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • CLDN18 • CLDN8 • IFNG • IL6 • TNFA

Zai Lab to Present New Oncology Research at 2022 Society for Immunotherapy of Cancer Annual Meeting (GlobeNewswire) - "Zai Lab Limited...will present new data from its internal immuno-oncology pipeline at the upcoming Society for Immunotherapy of Cancer (SITC) Annual Meeting on November 8-12, 2022 in Boston, Mass. These presentations will focus on two key global discovery programs: ZL-1211, an anti-CLDN18.2 antibody and ZL-1218, an anti-CCR8 antibody."

P1/2 data • Preclinical • Oncology • Solid Tumor

Zai Lab to Present New Oncology Research at 2022 AACR Annual Meeting (GlobeNewswire) - "Three poster presentations will highlight additional key programs in Zai Lab’s internal oncology pipeline....Preclinical data will measure the enhanced antitumor effect by combining ZL-1201 with the current standard of care antibody treatments in hematologic and solid tumor models. Data from ZL-1211, a CLDN18.2-specific monoclonal antibody will be presented with preclinical results supporting effective targeting of CLDN18.2+ gastric cancer, including CLDN18.2-low expressing malignancies....Another presentation will feature the discovery and development of ZL-2201, a novel, orally bioavailable, selective DNA-PK inhibitor."

Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Zai Lab Announces Financial Results and Corporate Updates for Twelve Months Ended December 31, 2021 (GlobeNewswire) - "Anticipated 2022 Zai Milestone: Simurosertib: Initiate a Phase 2 biomarker-driven proof-of-concept study in the second quarter of 2022; ZL-1201: Determine a recommended Phase 2 dose in the ongoing Phase 1 trial in mid-2022; Present preclinical data of ZL-1201 in combination with standard of care therapeutic antibodies in hematologic and solid tumor models at the 2022 AACR annual meeting; ZL-1211: Present preclinical data of ZL-1211 (Claudin18.2), ZL-2201 (DNA-PK), and ZL-1218 (CCR8) at the 2022 AACR annual meeting."

Clinical • New P2 trial • Preclinical • Hematological Malignancies • Oncology • Solid Tumor

A Study of ZL-1211 in Patients With Advanced Solid Tumor (clinicaltrials.gov) - P1/2 | N=162 | Recruiting | Sponsor: Zai Biopharmaceutical (Suzhou) Co., Ltd. | Initiation date: Oct 2021 ➔ Jan 2022

Trial initiation date • Oncology • Solid Tumor • CLDN18

A Study of ZL-1211 in Patients With Advanced Solid Tumor (clinicaltrials.gov) - P1/2; N=162; Recruiting; Sponsor: Zai Biopharmaceutical (Suzhou) Co., Ltd.

Clinical • New P1/2 trial • Oncology • Solid Tumor • CLDN18

[VIRTUAL] ZL-1211 exhibits broad anti-tumor activity in CLDN18.2 high- and low-expressing models (AACR 2021) - "Together, our data suggest that ZL-1211 might provide therapeutic benefit for a wider spectrum of low- and high-CLDN18.2 expressing tumors than the leading clinical benchmark. A Ph1 dose escalation study to assess the safety and preliminary efficacy of ZL-1211 is planned."

Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18