A Phase I/II, First-in-Human, Open-Label, Dose Escalation Study of ZL- 1211 in Patients With Unresectable or Metastatic Solid Tumor
Overview
- Phase
- Phase 1
- Intervention
- ZL-1211
- Conditions
- Advanced Solid Tumor
- Sponsor
- Zai Biopharmaceutical (Suzhou) Co., Ltd.
- Enrollment
- 34
- Locations
- 21
- Primary Endpoint
- Phase I ：MTD or MAD
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients are eligible to be included in the study only if all the following inclusion criteria apply:
- •Adults≥ 18 years of age.
- •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.
- •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.
- •Patients with histologically or cytologically confirmed metastatic or locally advanced solid tumors, refractory to standard treatment
- •Evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Adequate hepatic function
- •Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; AST or ALT ≤ 5 × ULN if liver metastases are present.
Exclusion Criteria
- •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.
- •Any uncontrolled active infection.
- •Previous exposure to any CLDN18.2 antibody or CLDN18.2 chimeric antigen receptor T cell therapy.
- •Newly diagnosed or symptomatic brain metastases anticonvulsants are allowed.
- •Severe cardiovascular disease; New York Heart Association Class II-IV heart failure within 6 months of screening; uncontrolled arrhythmia within 6 months of screening.
- •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.
- •Major surgery within 4 weeks prior to first dose; minor surgery within 2 weeks prior to first dose.
- •Symptomatic intrinsic lung disease (chronic obstructive pulmonary disease, pulmonary fibrosis).
- •Gastrointestinal abnormalities including:
- •Documented unresolved gastric outlet obstruction or persistent vomiting defined as ≥ 3 episodes within 24 hours.
Arms & Interventions
ZL-1211 monotherapy
Intervention: ZL-1211
Outcomes
Primary Outcomes
Phase I ：MTD or MAD
Time Frame: 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
Time Frame: Approximately 10 months
Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Phase II: preliminary antitumor activity
Time Frame: 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 Outcomes
- Phase I and Phase II: immunogenicity(Approximately 10 months)
- Phase I and Phase II: pharmacokinetics (PK):Cmax(Approximately 10 months)
- Phase I and Phase II: pharmacokinetics (PK):AUC(Approximately 10 months)
- Phase I and Phase II: pharmacokinetics (PK):t1/2(Approximately 10 months)
- Phase I and Phase II: pharmacokinetics (PK):Ctrough(Approximately 10 months)
- Phase I and Phase II: pharmacokinetics (PK):Tmax(Approximately 10 months)
- Phase I and Phase II: pharmacokinetics (PK):CL(Approximately 10 months)
- Phase II: preliminary antitumor activity(Approximately 10 months)
- Phase I and Phase II: pharmacokinetics (PK):Vss(Approximately 10 months)