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

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.

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) v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• 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.
• Adequate renal function, as defined by serum creatinine < 1.5 × ULN OR calculated creatinine CL > 40 mL/min, Cockroft-Gault Equation:
• Hematological function defined as:

• Absolute neutrophil count ≥ 1.5 × 109/L without growth factor support in the 2 weeks prior to screening.
• Platelet count ≥ 100 × 109/L without transfusion in the 2 weeks prior to screening.
• Hemoglobin ≥ 9 g/dL without transfusion in the 2 weeks prior to screening.
• Prothrombin time, international normalized ratio or/and activated partial thromboplastin time < 1.5 × ULN.
• Recovery, to Grade 0-1, from AEs related to prior anticancer therapy except alopecia, < Grade 2 sensory neuropathy, lymphopenia.

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.
• Active peptic ulcer disease required treatment in the past 3 months.
• Gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.
• Documented active colitis within 4 weeks prior to study entry, including infectious colitis, radiation colitis and ischemic colitis.
• History of ulcerative colitis or Crohn's disease.
• Patient has received systemic immunosuppressive therapy, including systemic corticosteroids 2 weeks prior to first dose of study drug.