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

Sponsor
Zai Biopharmaceutical (Suzhou) Co., Ltd. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05065710
Collaborator
(none)
162
Enrollment
9
Locations
1
Arm
32.4
Anticipated Duration (Months)
18
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
162 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
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.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.
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jan 19, 2022
Anticipated Primary Completion Date :
Feb 1, 2024
Anticipated Study Completion Date :
Oct 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: ZL-1211 monotherapy

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

Outcome Measures

Primary Outcome Measures

  1. 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

  2. Phase I and Phase II: safety and tolerability [Approximately 10 months]

    Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  3. 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 Outcome Measures

  1. Phase I and Phase II: pharmacokinetics (PK):AUC [Approximately 10 months]

    Area under the curve (AUC)

  2. Phase I and Phase II: pharmacokinetics (PK):Cmax [Approximately 10 months]

    Maximum serum concentration (Cmax)

  3. Phase I and Phase II: pharmacokinetics (PK):Tmax [Approximately 10 months]

    Time to reach Cmax (Tmax)

  4. Phase I and Phase II: pharmacokinetics (PK):Ctrough [Approximately 10 months]

    Ctrough

  5. Phase I and Phase II: pharmacokinetics (PK):Vss [Approximately 10 months]

    Volume of distribution at steady state (Vss)

  6. Phase I and Phase II: pharmacokinetics (PK):CL [Approximately 10 months]

    Clearance (CL)

  7. Phase I and Phase II: pharmacokinetics (PK):t1/2 [Approximately 10 months]

    Half-life (t1/2)

  8. Phase I and Phase II: immunogenicity [Approximately 10 months]

    Incidence of anti-drug antibodies (ADAs)

  9. Phase I and Phase II: immunogenicity [Approximately 10 months]

    Quantity of anti-drug antibodies (ADAs)

  10. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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

  8. Total bilirubin ≤ 1.5 × upper limit of normal (ULN).

  9. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; AST or ALT ≤ 5 × ULN if liver metastases are present.

  10. Adequate renal function, as defined by serum creatinine < 1.5 × ULN OR calculated creatinine CL > 40 mL/min, Cockroft-Gault Equation:

  11. Hematological function defined as:

  12. Absolute neutrophil count ≥ 1.5 × 109/L without growth factor support in the 2 weeks prior to screening.

  13. Platelet count ≥ 100 × 109/L without transfusion in the 2 weeks prior to screening.

  14. Hemoglobin ≥ 9 g/dL without transfusion in the 2 weeks prior to screening.

  15. Prothrombin time, international normalized ratio or/and activated partial thromboplastin time < 1.5 × ULN.

  16. 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:

  10. Documented unresolved gastric outlet obstruction or persistent vomiting defined as ≥ 3 episodes within 24 hours.

  11. Active peptic ulcer disease required treatment in the past 3 months.

  12. Gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.

  13. Documented active colitis within 4 weeks prior to study entry, including infectious colitis, radiation colitis and ischemic colitis.

  14. History of ulcerative colitis or Crohn's disease.

  15. Patient has received systemic immunosuppressive therapy, including systemic corticosteroids 2 weeks prior to first dose of study drug.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Zai Lab Site 2012 Scottsdale Arizona United States 85258
2 Zai Lab Site 2016 Lynwood California United States 90262
3 Zai Lab Site 2014 Indianapolis Indiana United States 46250
4 Zai Site 2020 Hackensack New Jersey United States 07601
5 Zai Lab Site 2015 Cincinnati Ohio United States 45219
6 Zai Lab Site 2011 Nashville Tennessee United States 37203
7 Zai Lab Site 2023 Fairfax Virginia United States 22031
8 Zai Lab Site 2013 Spokane Washington United States 99208
9 Zai Lab Site 2022 Tacoma Washington United States 98405

Sponsors and Collaborators

  • Zai Biopharmaceutical (Suzhou) Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Zai Biopharmaceutical (Suzhou) Co., Ltd.
ClinicalTrials.gov Identifier:
NCT05065710
Other Study ID Numbers:
  • ZL-1211-001
First Posted:
Oct 4, 2021
Last Update Posted:
Aug 19, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Zai Biopharmaceutical (Suzhou) Co., Ltd.
CLDN18.2
Solid tumor
Additional relevant MeSH terms:
Neoplasms

Study Results

No Results Posted as of Aug 19, 2022