Clinical trial NCT05164458: Safety and Efficacy of IBI389 Single Agent, and in Combination With Sintilimab, in Patients With Advanced Malignancies
Official title: A Phase Ia/Ib, Open Label, Multicenter Study of the Safety and Efficacy of IBI389 Single Agent, and in Combination With Sintilimab, Administered to Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2021-12-20
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with AEs and SAEs
timeFrame: up to 2 years after enrollment
measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: up to 28 Days following first dose
Secondary outcomes:
measure: Pharmacokinetics: AUC
timeFrame: up to 2 years after enrollment
measure: Cmax
timeFrame: up to 2 years after enrollment
measure: Immunogenicity: Percentage of ADA positive subjects
timeFrame: up to 2 years after enrollment
measure: Preliminary anti-tumor activity of IBI389 (Objective Response Rate)
timeFrame: up to 2 years after enrollment
Other outcomes:
Locations:
city: Chendu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
References: