Advanced Solid Tumors
Conditions
Brief summary
This study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of IBI389 as a single agent, and in combination with sintilimab, and (or) chemotherapy in patients with advanced or metastatic solid tumors.
Detailed description
The study consists of a dose escalation phase (Ia) and a dose expansion phase (Ib). Phase Ia is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for IBI389 as a single agent, and in combination with sintilimab. Phase (Ib) is a multi-cohort trial of CLDN18.2 positive solid tumors to evaluate safety and preliminary efficacy of IBI389 in combination with sintilimab and (or) chemotherapy or IBI389 monotherapy.
Interventions
DRUGIBI 308 injection
IBI308 IV 200mg Q3W Day1
DRUGIBI 389 Injection
IBI 389 IV Q2\ Q3W Day 1
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provide signed informed consent; 2. Male or female aged at 18-75 (inclusive) years; 3. Expected survival ≥12 weeks; 4. ECOG PS score 0 or 1; 5. Provide archival or fresh tissues for CLDN18.2 expression analysis; 6. Adequate laboratory parameters; 7. Suffer from advanced or metastatic malignant local solid tumors confirmed by histological diagnosis and meet the criteria of the enrolled group as follows: Ia: The subjects for whom no standard treatment regimens are available or who is intolerable to standard treatments. Ib: pancreatic carcinoma, gastric adenocarcinoma, advanced or metastatic solid tumors
Exclusion criteria
1. Participate in another interventional clinical study, except for the observational (non-interventional) clinical study or the survival follow-up phase of the interventional study. 2. Any investigational drugs received within 4 weeks prior to the first study treatment. 3. Receive the last dose of anti-tumor therapy within 4 weeks before the first dose of study therapy. 4. Immunosuppressive drugs were used within 4 weeks prior to the first administration of the study drug. 5. Medication requiring long-term systemic hormones or any other immunosuppression therapy. 6. Major surgical procedures (craniotomy, thoracotomy, or laparotomy) or unhealed wounds, ulcers, or fractures were performed within 4 weeks prior to the first dose of study therapy. 7. There was unrecovered toxicity (excluding hair loss or fatigue) according to NCI CTCAE v5.0 induced by previous antitumor therapy (24 weeks before the first dose of study), and there were unrecovered immune-related adverse events (irAE) associated with immunotherapy. 8. Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases, or leptomeningeal disease. 9. History of autoimmune disease , present active autoimmune disease or inflammatory diseases 10. Present or history of pulmonary diseases such as interstitial pneumonia, pneumoconiosis, drug-related pneumonia, pulmonary fibrosis, active pulmonary infection, severely impaired pulmonary function. 11. Positive human immunodeficiency virus (HIV) test. 12. Active hepatitis B or C, or tuberculosis. 13. History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. 14. History of gastrointestinal perforation and/or fistula at 6 months prior to study inclusion. 15. Hydrothorax, ascites, and pericardial effusion with clinical symptoms requiring drainage. 16. Known history of hypersensitivity to any components of the IBI389 or Sintilimab. 17. Uncontrolled complications of disease. 18. Other acute or chronic illness, mental illness, or abnormal laboratory test values that may increase the risk of study participation or administration of study drugs, or interfere with the interpretation of study results. 19. Pregnant or nursing females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with AEs and SAEs | up to 2 years after enrollment | To evaluate the safety and tolerability of IBI389 alone or in combination with Sintilimab \[Adverse events (AEs), Serious Adverse Events (SAEs) \] |
| Percentage of Participants with Dose-Limiting Toxicities (DLTs) | up to 28 Days following first dose | To evaluate the safety and tolerability of IBI389 alone or in combination with Sintilimab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: AUC | up to 2 years after enrollment | The area under the curve (AUC) of serum concentration of the drug after the administration. |
| Cmax | up to 2 years after enrollment | Maximum concentration (Cmax) of the drug after administration |
| Immunogenicity: Percentage of ADA positive subjects | up to 2 years after enrollment | Immunogenicity: Number of Anti-Drug Antibodies (ADA) positive subjects will be counted and percentage of ADA positive subjects will be calculated to evaluate immunogenicity of IBI389. |
| Preliminary anti-tumor activity of IBI389 (Objective Response Rate) | up to 2 years after enrollment | Objective Response Rate (ORR) is the percentage of Complete Response (CR) plus partial response (PR) assessed by RECIST v1.1 criteria for solid tumors. |
Countries
China
Contacts
Primary Contactxiaoqin ruan
Outcome results
None listed