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

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.

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.