A Study of ZL-1211 in Patients With Advanced Solid Tumor

Conditions

Advanced Solid Tumor

Keywords

CLDN18.2, Solid tumor

Brief summary

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.

Detailed description

The study consists of two stages, Phase I -Dose Escalation Phase to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of ZL-1211, and Phase II -Cohort Expansion Phase to further define the safety and initial antitumor activity of ZL-1211 with the dose established in the Dose Escalation Phase. The trial was intended to be a Phase 1/2 trial but the Phase 2 was not initiated.

Sunil Sharma, Alexander Starodub, Nong Xu, Arvind Chaudhry, Meili Sun et al. (11 authors)

Journal of Clinical Oncology2023-06-017 citations

10.1200/jco.2023.41.16_suppl.2537

Abstract 4531: 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

Zhen Luo, Xiao Wang, Xuehuo Zeng, Jiaqing Yi, Tegan Burns et al. (10 authors)

Cancer Research2023-04-04

10.1158/1538-7445.am2023-4531

809 Anti-CLDN18.2 antibody ZL-1211 enhances anti-tumor activities in combination with chemotherapy in gastric cancer models

Anthony Cao, Qiuping Ye, Karl Hsu, Hua Gong, Haiying Zhou et al. (7 authors)

Regular and Young Investigator Award Abstracts2022-11-011 citations

10.1136/jitc-2022-sitc2022.0809

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

Hiroyasu Konno, Tracey Lin, Renyi Wu, Xinchuan Dai, Shou Li et al. (21 authors)

Cancer Research Communications2022-08-099 citations

10.1158/2767-9764.crc-22-0216

Abstract 621: 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

Hiroyasu Konno, Tracey Lin, Bee-Chun Sun, Renyi Wu, Christopher W. Szeto et al. (8 authors)

Cancer Research2022-06-15

10.1158/1538-7445.am2022-621

Interventions

DRUGZL-1211

Phase 1 dose escalation part will enroll about 12-42 patients, Phase 2 dose expansion part will enroll about 15-40 patients in each cohort

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Phase I, the Dose Escalation Phase of the study will enroll patients with locally advanced or metastatic solid tumors of any histology with positive CLDN18.2. Phase II, the Cohort Expansion Phase of the study, will be conducted after determination of the dose level (RP2D) for cohort expansion based on the results of Phase I to explore the preliminary efficacy.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

Patients are eligible to be included in the study only if all the following inclusion criteria apply: 1. Adults≥ 18 years of age. 2. Willing and able to provide signed and dated informed consent prior to any study related procedures and willing and able to comply with all study procedures. 3. All patients from Phase I and Phase II are required to provide tumor tissue for CLDN18.2 IHC assessment, and only patients with CLDN18.2-positive tumors will be included in this study. 4. Patients with histologically or cytologically confirmed metastatic or locally advanced solid tumors, refractory to standard treatment 5. Evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 7. Adequate hepatic function 1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN). 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; AST or ALT ≤ 5 × ULN if liver metastases are present. 8. Adequate renal function, as defined by serum creatinine \< 1.5 × ULN OR calculated creatinine CL \> 40 mL/min, Cockroft-Gault Equation: 9. Hematological function defined as: 1. Absolute neutrophil count ≥ 1.5 × 109/L without growth factor support in the 2 weeks prior to screening. 2. Platelet count ≥ 100 × 109/L without transfusion in the 2 weeks prior to screening. 3. Hemoglobin ≥ 9 g/dL without transfusion in the 2 weeks prior to screening. 10. Prothrombin time, international normalized ratio or/and activated partial thromboplastin time \< 1.5 × ULN. 11. Recovery, to Grade 0-1, from AEs related to prior anticancer therapy except alopecia, \< Grade 2 sensory neuropathy, lymphopenia.

Exclusion criteria

1. Patient with known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome related illness or known active or chronic hepatitis B virus infection or hepatitis C virus. 2. Any uncontrolled active infection. 3. Previous exposure to any CLDN18.2 antibody or CLDN18.2 chimeric antigen receptor T cell therapy. 4. Newly diagnosed or symptomatic brain metastases anticonvulsants are allowed. 5. Severe cardiovascular disease; New York Heart Association Class II-IV heart failure within 6 months of screening; uncontrolled arrhythmia within 6 months of screening. 6. Anticancer therapy or radiation therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to screening; palliative radiotherapy within 2 weeks prior to screening. 7. Major surgery within 4 weeks prior to first dose; minor surgery within 2 weeks prior to first dose. 8. Symptomatic intrinsic lung disease (chronic obstructive pulmonary disease, pulmonary fibrosis). 9. Gastrointestinal abnormalities including: 1. Documented unresolved gastric outlet obstruction or persistent vomiting defined as ≥ 3 episodes within 24 hours. 2. Active peptic ulcer disease required treatment in the past 3 months. 3. Gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy. 4. Documented active colitis within 4 weeks prior to study entry, including infectious colitis, radiation colitis and ischemic colitis. 5. History of ulcerative colitis or Crohn's disease. 10. Patient has received systemic immunosuppressive therapy, including systemic corticosteroids 2 weeks prior to first dose of study drug.

Design outcomes

Primary

Measure	Time frame	Description
Phase I ：MTD or MAD	One month	To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of ZL-1211
Phase I and Phase II: safety and tolerability	Approximately 10 months	Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Phase II: preliminary antitumor activity	Approximately 10 months	Objective response rate defined as the proportion of patients with partial response (PR) proportion of patients with partial response (PR) or complete response (CR) based on Investigator assessment of tumor lesions per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary

Measure	Time frame	Description
Phase I and Phase II: pharmacokinetics (PK):AUC	Approximately 10 months	Area under the curve (AUC)
Phase I and Phase II: pharmacokinetics (PK):Cmax	Approximately 10 months	Maximum serum concentration (Cmax)
Phase I and Phase II: pharmacokinetics (PK):Tmax	Approximately 10 months	Time to reach Cmax (Tmax)
Phase I and Phase II: pharmacokinetics (PK):Ctrough	Approximately 10 months	Ctrough
Phase I and Phase II: immunogenicity	Approximately 10 months	Incidence of anti-drug antibodies (ADAs)
Phase II: preliminary antitumor activity	Approximately 10 months	Duration of response (DOR), defined as the time from the first date of objective response (CR or PR) to the first documented date of disease progression per RECIST v1.1 or the date of death due to any cause, whichever occurs first
Phase I and Phase II: pharmacokinetics (PK):t1/2	Approximately 10 months	Half-life (t1/2)
Phase I and Phase II: pharmacokinetics (PK):Vss	Approximately 10 months	Volume of distribution at steady state (Vss)
Phase I and Phase II: pharmacokinetics (PK):CL	Approximately 10 months	Clearance (CL)

Countries

China, United States

Outcome results

None listed