主要目的 I期：确定ZL-1211的最大耐受剂量（MTD）或最大给药剂量（MAD）（如果未确定MTD），并确定ZL-1211的II期推荐剂量（RP2D） I期和II期：评价ZL-1211在不可切除的或转移性实体瘤患者中的安全性和耐受性 II期：评估ZL-1211的初步抗肿瘤活性次要目的 I期和II期：评估ZL-1211的药代动力学（PK） I期和II期：评估CLDN18.2表达水平与ZL-1211治疗应答的相关性 I期和II期：评估ZL-1211的免疫原性 II期：评估ZL-1211的初步抗肿瘤活性探索性目的 II期：进一步评估ZL-1211的初步抗肿瘤活性评估CLDN18.2的表达用以在未来开发CLDN18.2免疫组化(IHC)的伴随诊断。这将在所有纳入研究的患者样本中进行评估。评估肿瘤免疫微环境（作为ZL-1211有效性的潜在预测性生物标志物）。对于在中国大陆研究中心入组的患者，将不包括该目的。

[Translation]

Primary Objectives Phase I: Determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of ZL-1211 (if MTD is not determined), and determine the recommended Phase II dose (RP2D) of ZL-1211 Phase I and Phase II: Evaluate the safety and tolerability of ZL-1211 in patients with unresectable or metastatic solid tumors Phase II: Evaluate the preliminary anti-tumor activity of ZL-1211 Secondary Objectives Phase I and Phase II: Evaluate the pharmacokinetics (PK) of ZL-1211 Phase I and Phase II: Evaluate the correlation between CLDN18.2 expression level and ZL-1211 treatment response Phase I and Phase II: Evaluate the immunogenicity of ZL-1211 Phase II: Evaluate the preliminary anti-tumor activity of ZL-1211 Exploratory Objectives Phase II: Further evaluate the preliminary anti-tumor activity of ZL-1211 Evaluate the expression of CLDN18.2 for the future development of a companion diagnostic for CLDN18.2 immunohistochemistry (IHC). This will be assessed in all patient samples included in the study. Assess the tumor immune microenvironment (as a potential predictive biomarker for ZL-1211 effectiveness). This objective will not be included for patients enrolled at the mainland China study centers.

Start Date21 Jun 2022

Sponsor / Collaborator

Zai Biopharmaceutical (Suzhou) Co., Ltd.

NCT05065710 / CompletedPhase 1

A Phase I, First-in-Human, Open-Label, Dose Escalation Study of ZL- 1211 in Patients With Unresectable or Metastatic Solid Tumor

This study is a Phase I/II, open-label, dose escalation, and cohort expansion study designed to characterize the safety, tolerability, pharmacokinetic (PK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of ZL-1211 administered by IV infusion on a every 2 weeks (Q2W) schedule.

Start Date19 Jan 2022

Sponsor / Collaborator

Zai Biopharmaceutical (Suzhou) Co., Ltd.

100 Clinical Results associated with ZL-1211

100 Translational Medicine associated with ZL-1211

100 Patents (Medical) associated with ZL-1211

Literatures (Medical) associated with ZL-1211

07 Sep 2022·Cancer Research Communications

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

Article

Author: Kabbarah, Omar ; Konno, Hiroyasu ; Chen, Min ; Sun, Bee-Chun ; Wang, Grace ; Kang, Lishan ; Wan, Bing ; Bellovin, David ; Dai, Xinchuan ; Lin, Tracey ; Wang, Lina ; Li, Wenying ; Li, Shou ; Wu, Renyi ; Luo, Zhen ; Chen, Yuping ; Huang, Tom ; Ye, Qiuping ; Szeto, Christopher ; Hsu, Karl ; Zhang, John

CLDN18.2 (Claudin18.2)-targeting therapeutic antibodies have shown promising clinical efficacy in approximately 30% of gastric cancers expressing high levels of CLDN18.2 and less pronounced activity in low expressing malignancies. Here, we report that ZL-1211 is a mAb targeting CLDN18.2 engineered to promote enhanced antibody-dependent cellular cytotoxicity (ADCC) with the goal of achieving more potent activity in a wider spectrum of high- and low-CLDN18.2 expressing tumors. ZL-1211 demonstrated more robust in vitro ADCC activity than clinical benchmark not only in CLDN18.2-high but also CLDN18.2-low expressing gastric tumor cell lines. Greater antitumor efficacy was also observed in mouse xenograft models. Natural killer (NK) cell played critical roles in ZL-1211 efficacy and NK-cell depletion abrogated ZL-1211–mediated ADCC activity in vitro. ZL-1211 efficacy in vivo was also dependent on the presence of an NK compartment. Strikingly, NK cells strongly induced an inflammatory response in response to ZL-1211 treatment, including increased IFNγ, TNFα, and IL6 production, and were recruited into tumor microenvironment in patient-derived gastric tumors expressing CLDN18.2 upon ZL-1211 treatment to lyse the tumor cells. Taken together, our data suggest that ZL-1211 more effectively targets CLDN18.2-high gastric cancers as well as -low expressing malignancies that may not be eligible for treatment with the leading clinical benchmark by inducing enhanced ADCC response and activating NK cells with robust inflammation to enhance antitumor efficacy. Clinical activity of ZL-1211 is currently under evaluation in a phase I clinical trial (NCT05065710).Significance: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.

100 Deals associated with ZL-1211

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
CLDN18.2 positive Solid Tumors	Phase 2	US	Zai Biopharmaceutical (Suzhou) Co., Ltd.	23 Nov 2021
Pancreatic Cancer	Phase 1	CN	Zai Lab (Shanghai) Co., Ltd.	30 May 2023
Stomach Cancer	Phase 1	CN	Zai Lab (Shanghai) Co., Ltd.	30 May 2023
Advanced Malignant Solid Neoplasm	Phase 1	US	Zai Biopharmaceutical (Suzhou) Co., Ltd.	19 Jan 2022
Advanced Malignant Solid Neoplasm	Phase 1	CN	Zai Biopharmaceutical (Suzhou) Co., Ltd.	19 Jan 2022
Metastatic Solid Tumor	Phase 1	US	Zai Biopharmaceutical (Suzhou) Co., Ltd.	19 Jan 2022
Metastatic Solid Tumor	Phase 1	CN	Zai Biopharmaceutical (Suzhou) Co., Ltd.	19 Jan 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05065710 (ASCO2023) Manual	Phase 1/2	Metastatic Solid Tumor	19	ZL-1211	(lorgaltpcm) = plmpvjdauu rqcpirczah (rxvpmjircc ) View more	Positive	26 May 2023

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