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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05065710
• Other study ID #: ZL-1211-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 19, 2022
• Est. completion date: October 2024

Study information

• Verified date: November 2023
• Source: Zai Lab (Hong Kong), Ltd.
• Contact: ZL-1211-001 Study Director
• Phone: +862161632588
• Email: Study-ZL-1211-001[@]zailaboratory.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: October 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• ZL-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

Locations

Country	Name	City	State
China	Zai Lab Site 1548	Beijing	Beijing
China	Zai Lab Site 1712	Chengdu	Sichuan
China	Zai Lab Site 1529	Hangzhou	Zhejiang
China	Zai Lab Site 1714	Hangzhou	Zhejiang
China	Zai Lab Site 1551	Harbin	Heilongjiang
China	Zai Lab Site 1725	Hefei	Anhui
China	Zai Lab Site 1539	Jinan	Shandong
China	Zai Lab Site 1542	Shanghai	Shanghai
China	Zai Lab Site 1537	Wuhan	Hubei
China	Zai Lab Site 1202	Zhengzhou	Henan
China	Zai Lab Site 1549	Zhengzhou	Henan
United States	Zai Lab Site 2015	Cincinnati	Ohio
United States	Zai Lab Site 2023	Fairfax	Virginia
United States	Zai Site 2020	Hackensack	New Jersey
United States	Zai Lab Site 2014	Indianapolis	Indiana
United States	Zai Lab Site 2016	Lynwood	California
United States	Zai Lab Site 2011	Nashville	Tennessee
United States	Zai Lab Site 2025	New York	New York
United States	Zai Lab Site 2012	Scottsdale	Arizona
United States	Zai Lab Site 2013	Spokane	Washington
United States	Zai Lab Site 2022	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Zai Biopharmaceutical (Suzhou) Co., Ltd.

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I :MTD or MAD	To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of ZL-1211	One month
Primary	Phase I and Phase II: safety and tolerability	Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v5.0	Approximately 10 months
Primary	Phase II: preliminary antitumor activity	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	Approximately 10 months
Secondary	Phase I and Phase II: pharmacokinetics (PK):AUC	Area under the curve (AUC)	Approximately 10 months
Secondary	Phase I and Phase II: pharmacokinetics (PK):Cmax	Maximum serum concentration (Cmax)	Approximately 10 months
Secondary	Phase I and Phase II: pharmacokinetics (PK):Tmax	Time to reach Cmax (Tmax)	Approximately 10 months
Secondary	Phase I and Phase II: pharmacokinetics (PK):Ctrough	Ctrough	Approximately 10 months
Secondary	Phase I and Phase II: pharmacokinetics (PK):Vss	Volume of distribution at steady state (Vss)	Approximately 10 months
Secondary	Phase I and Phase II: pharmacokinetics (PK):CL	Clearance (CL)	Approximately 10 months
Secondary	Phase I and Phase II: pharmacokinetics (PK):t1/2	Half-life (t1/2)	Approximately 10 months
Secondary	Phase I and Phase II: immunogenicity	Incidence of anti-drug antibodies (ADAs)	Approximately 10 months
Secondary	Phase I and Phase II: immunogenicity	Quantity of anti-drug antibodies (ADAs)	Approximately 10 months
Secondary	Phase II: preliminary antitumor activity	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	Approximately 10 months