Advanced solid tumors
Conditions
Interventions
0.3mg/kg-12mg/kg:PM1032 Injection
Sponsors
Shanghai Orient Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntary participation in clinical study; fully understand the study and sign informed consent voluntarily; willing to follow and able to complete all test procedures; 2. Male or female aged 18 to 75 years; 3. Subjects with malignant tumor confirmed by histology or cytology, Subjects with advanced malignant solid tumors who have no standard treatment, have failed standard treatment or are not eligible for standard treatment: 3.1) Phase I dose escalation stage: gastric/gastroesophageal junction adenocarcinoma, esophageal cancer, pancreatic cancer, etc.; 3.2) Phase I dose expansion stage, phase IIa dose expansion: gastric/gastroesophageal junction adenocarcinoma, esophageal cancer, pancreatic cancer, other tumors(Biliary tract malignancies, colorectal cancer, mucinous ovarian cancer, etc.); CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay in central laboratory. 4. Adequate organ function; 5. ECOG score was 0-1; 6. Expected survival >=12 weeks; 7.According to RECIST1.1, there are at least one evaluable tumor lesion during dose escalation period, and at least one measurable tumor lesion during dose expansion period and phase IIa expansion stage; 8. Subjects shall provide tumor tissue specimens within 24 months or by biopsy for CLDN18.2 analysis: 8.1) Phase I dose escalation period: try to obtain tumor lesion; 8.2) Phase I dose expansion period and phase IIa expansion stage: must provide tumor lesion. If achieved lesion cannot be obtained, lesions must be collected by biopsy with 28 days before the study treatment (bone biopsy are not accepted) ; if the subject cannot provide lesions that meet the above time limit due to special reasons, the subject can aso participate in the screening with the consent of the sponsors medical monitor; subjects tumor is positive for CLDN18.2 expression. 9. Pre-menopausal female subjects with negative blood pregnancy results within 7 days prior to the study treatment, and agree to abstain from sex or use medically approved effective contraceptive measures for 6 months from the date of signing the informed consent form to the end of the last medication; 10. Male subjects are agree to abstain from sex or use medically approved effective contraceptive methods for 6 months from the date of signing the informed consent form to the end of the last medication, and do not donate sperm during this period;
Exclusion criteria
Exclusion criteria: 1. History of severe allergic, severe allergy to drugs or known allergy to any component of the drug in this study; 2. Previous exposure to immune costimulatory molecule agonists such as 4-1BB mono/bispecific antibodies etc; 3.Patients who received CLDN18.2-targeted mono/bispecific antibodies or cell therapy; 4. History of hepatitis (e.g., non-alcohol steatohepatitis, alcohol related, auto-immune related) or cirrhosis; 5. HBsAg or HBcAb positive and HBV-DNA > 500 IU/mL or the lower limit of the site test [only if the lower limit of the site test is above 500 IU/ml]); HCV antibody positive and HCV-RNA above the lower limit of the site test, allowing the patients receiving prophylactic antiviral therapy other than interferon; 6.Subjects who have the following gastrointestinal symptoms: 6.1) Uncontrollable vomiting within 4 weeks prior to the first dose of study treatment; 6.2) Active peptic ulcer requiring treatment within 3 months prior to the first dose of study treatment; 6.3) Active colitis, including infectious, radioactive, ischemic enteritis within 4 weeks prior to the first dose of study treatment; 6.4) Patients has gastric bleeding or gastric perforation as judged by the investigator; 7. Cerebral parenchymal metastasis or meningeal metastasis with clinical symptoms were deemed unsuitable for inclusion by the investigator; 8.Current definite interstitial lung disease or non-infectious pneumonitis, except for local radiotherapy; 9. Current presence of uncontrolled pleural, pericardial, and peritoneal effusions; 10.Patients has currently active infections requiring intravenous ant-infective therapy; 11. Patients with active autoimmune disease or a history of autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for clinically stable autoimmune thyroid disease, type I diabetes patients; 12.Patients who have grade >=3 immune-mediated adverse event and grade >=2 immune-related myocarditis adverse event that associated with a prior immunotherapy; 13. Adverse reactions to previous antitumor therapy have not recovered to NCI-CTCAE V5.0 rating 10 mg/day or equivalent dose of the similar drug) or other immunosuppressive therapy within 2 weeks before the trial treatment; The exceptions including local, ocular, intraarticular, intranasal, and inhaled glucocorticoids treatment; Short-term use of glucocorticoids for prophylactic treat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limited toxicity within 21 days after first administration;Assess the incidence and severity of treatment-related adverse events;Objective Response rate assessed by Independent Review Committee(per RECIST v1.1 criteria); | — |
Secondary
| Measure | Time frame |
|---|---|
| PM1032 anti-drug antibody;Pharmacokinetic characteristics; | — |
Countries
China
Contacts
Public ContactYe Guo
Shanghai Orient Hospital
Outcome results
None listed