Overview

This is a multi-center, open-label, Phase Ⅰ/Ⅱ clinical study of ZG006 for the treatment of participants with small cell lung cancer or neuroendocrine carcinoma who had no standard treatment available, or were intolerant to standard treatment.

Eligibility

Inclusion Criteria:

• Fully understand the study and voluntarily sign the informed consent form;
• Male or female 18~75 years of age;
• Histologically or cytologically confirmed diagnosis of small cell lung cancer (SCLC), neuroendocrine carcinoma (NEC), who had no standard treatment available, or were intolerant to standard treatments;
• Archival tissue sample or fresh biopsy tissue sample must be available for DLL3 detection;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Life expectancy ≥ 3 months;
• Must have evaluable or measurable lesion. For lesions that have received radiation therapy, only after the progression of the lesions, they can be considered evaluable or measurable lesions;
• All adverse events from prior treatment have either returned to baseline or CTCAE 5.0 ≤ Grade 1, except for AEs not constituting a safety risk in the opinions of the investigators, e.g. alopecia, hypothyroidism which can be treated with a hormone replacement, etc.;
• Female and Male patients must agree to use a reliable form of contraception during the study treatment period and for at least 6 months after the last dose of the study drug.

Exclusion Criteria:

• Patients having received any of the following treatments:

        Anti-DLL3 and anti-CD3 drugs (including investigational drugs); Chemotherapy, biotherapy,
        endocrine therapy (except for hormone replacement), and biological targeted medicines ≤ 4
        weeks before the study entry. Local palliative radiotherapy and a small molecule targeted
        therapy ≤ 2 weeks (or 5 half-lives, whichever is longer) before the study entry; Systemic
        immunosuppressive medications, such as corticosteroid (doses > 10 mg/day prednisone or
        equivalent dose) within 14 days prior to the study entry; Use of any vaccines against viral
        infections (COVID-19, influenza, varicella, etc.) within 4 weeks of study entry;
          -  Received any blood transfusion, EPO, G-CSF, albumin infusion and renal replacement
             therapy within 14 days prior to study entry.
          -  The main organ function meets any of the following criteria within 7 days prior to
             study entry; Hematological function: ANC < 1.5×10^9/L, PLT < 75×10^9/L, Hemoglobin
             (Hb) < 100 g/L; Hepatic function: Alanine aminotransferase (ALT) and aspartate
             aminotransferase (AST) ≥ 3×ULN, ALT and AST ≥ 5×ULN for liver metastases patients;
             Total bilirubin (TBIL) ≥ 1.5×ULN; albumin < 30g/L; Creatinine clearance
             (Cockcroft-Gault formula) < 50 mL/min; INR > 1.5 or APTT > 1.5×ULN;
          -  Medical history, computed tomography (CT) or magnetic resonance imaging (MRI) results
             indicate the existence of central nervous system (CNS) metastases; Note: Not
             applicable to the following conditions: subjects with stable CNS metastases;
          -  Uncontrollable third cavity effusion (e.g. a large amount of pleural effusion,
             ascites, or pericardial effusion, etc.) requiring repeated drainage, which was judged
             by the investigator to be unsuitable for study;
          -  Any other malignancy within 5 years (other than radically removed and has not recurred
             tumors including basal cell skin carcinoma, squamous cell skin carcinoma, superficial
             bladder cancer, localized prostate cancer, cervical cancer and other cancer in situ,
             etc.);
          -  Severe cardiac-cerebral vascular disease, including but not limited to:
        Acute myocardial infarction, unstable angina, stroke, or received coronary angioplasty or
        stent implantation within 6 months before study entry; New York Heart Association
        functional class II to IV congestive heart failure or left ventricular ejection fraction
        (LVEF) < 50% or the lower limit of normal; Uncontrollable hypertension (even though the
        best treatment is used but systolic blood pressure ≥ 140 mmHg and/or diastolic blood
        pressure ≥ 90 mmHg).
        QTc (F) interval prolonged in electrocardiography during the screening baseline period (>
        480 ms)
          -  History of autoimmune disease, including but not limited to systemic lupus
             erythematosus, nephritis, psoriasis, rheumatoid arthritis, inflammatory bowel disease,
             autoimmune hepatitis (except for the following: type I diabetes mellitus, skin
             diseases that do not require systemic treatment (such as vitiligo), controllable
             celiac disease, and childhood asthma that completely resolved in adulthood without
             intervention);
          -  Active infection (such as acute bacterial infection, tuberculosis, active hepatitis
             B/C, active syphilis, or active human immunodeficiency virus infection). Active
             hepatitis B is defined as: hepatitis B virus DNA titer > 10000 copies/mL or 2000
             IU/mL; active hepatitis C is defined as: a positive hepatitis C antibody and HCV viral
             load above the limit of quantification; active human immunodeficiency virus infection
             is defined as: antibody positive;
          -  Active neurologic paraneoplastic syndrome;
          -  Interstitial lung disease or non-infectious pneumonitis (other than radiation-induced
             pneumonia);
          -  Having received prior allogeneic stem cell transplantation or solid organ
             transplantation;
          -  Known allergy to other mAbs or any antibody excipients; the history of a severe
             allergic reaction, anaphylactoid or other hypersensitivity reactions to humanized
             antibodies or fusion proteins;
          -  Known history of diagnosed neurological or mental disorders, for example, epilepsy,
             dementia, etc.;
          -  A female who is pregnant or nursing;
          -  Patients were deemed unsuitable for participating in the study by the investigator for
             any reason.