Clinical trial NCT05065710: A Study of ZL-1211 in Patients With Advanced Solid Tumor
Official title: A Phase I, First-in-Human, Open-Label, Dose Escalation Study of ZL- 1211 in Patients With Unresectable or Metastatic Solid Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: CLDN18.2
Solid tumor
Lead sponsor: Zai Lab (Hong Kong), Ltd.
Sponsor class: INDUSTRY
First posted: 2021-10-04
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase I ：MTD or MAD
timeFrame: One month
measure: Phase I and Phase II: safety and tolerability
timeFrame: Approximately 10 months
measure: Phase II: preliminary antitumor activity
timeFrame: Approximately 10 months
Secondary outcomes:
measure: Phase I and Phase II: pharmacokinetics (PK):AUC
timeFrame: Approximately 10 months
measure: Phase I and Phase II: pharmacokinetics (PK):Cmax
timeFrame: Approximately 10 months
measure: Phase I and Phase II: pharmacokinetics (PK):Tmax
timeFrame: Approximately 10 months
measure: Phase I and Phase II: pharmacokinetics (PK):Ctrough
timeFrame: Approximately 10 months
measure: Phase I and Phase II: pharmacokinetics (PK):Vss
timeFrame: Approximately 10 months
measure: Phase I and Phase II: pharmacokinetics (PK):CL
timeFrame: Approximately 10 months
measure: Phase I and Phase II: pharmacokinetics (PK):t1/2
timeFrame: Approximately 10 months
measure: Phase I and Phase II: immunogenicity
timeFrame: Approximately 10 months
measure: Phase I and Phase II: immunogenicity
timeFrame: Approximately 10 months
measure: Phase II: preliminary antitumor activity
timeFrame: Approximately 10 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Zai Lab Site 2012
state: Arizona
city: Lynwood
country: United States
facility: Zai Lab Site 2016
state: California
city: Indianapolis
country: United States
facility: Zai Lab Site 2014
state: Indiana
city: Hackensack
country: United States
facility: Zai Site 2020
state: New Jersey
city: New York
country: United States
facility: Zai Lab Site 2025
state: New York
city: Cincinnati
country: United States
facility: Zai Lab Site 2015
state: Ohio
city: Nashville
country: United States
facility: Zai Lab Site 2011
state: Tennessee
city: Fairfax
country: United States
facility: Zai Lab Site 2023
state: Virginia
city: Spokane
country: United States
facility: Zai Lab Site 2013
state: Washington
city: Tacoma
country: United States
facility: Zai Lab Site 2022
state: Washington
city: Hefei
country: China
facility: Zai Lab Site 1725
state: Anhui
city: Beijing
country: China
facility: Zai Lab Site 1548
state: Beijing
city: Harbin
country: China
facility: Zai Lab Site 1551
state: Heilongjiang
city: Zhengzhou
country: China
facility: Zai Lab Site 1549
state: Henan
city: Zhengzhou
country: China
facility: Zai Lab Site 1202
state: Henan
city: Wuhan
country: China
facility: Zai Lab Site 1537
state: Hubei
city: Jinan
country: China
facility: Zai Lab Site 1539
state: Shandong
city: Shanghai
country: China
facility: Zai Lab Site 1542
state: Shanghai
city: Chengdu
country: China
facility: Zai Lab Site 1712
state: Sichuan
city: Hangzhou
country: China
facility: Zai Lab Site 1529
state: Zhejiang
city: Hangzhou
country: China
facility: Zai Lab Site 1714
state: Zhejiang
Study officials:
References: