Safety and Efficacy of IBI389 Single Agent, and in Combination With Sintilimab, in Patients With Advanced Malignancies

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: IBI 308 injection
* Drug: IBI 389 Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed informed consent; Male or female aged at 18-75 (inclusive) years; Expected survival ≥12 weeks; ECOG PS score 0 or 1; Provide archival or fresh tissues for CLDN18.2 expression analysis; Adequate laboratory parameters; 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: Participate in another interventional clinical study, except for the observational (non-interventional) clinical study or the survival follow-up phase of the interventional study. Any investigational drugs received within 4 weeks prior to the first study treatment. Receive the last dose of anti-tumor therapy within 4 weeks before the first dose of study therapy. Immunosuppressive drugs were used within 4 weeks prior to the first administration of the study drug. Medication requiring long-term systemic hormones or any other immunosuppression therapy. 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. 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. Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases, or leptomeningeal disease. History of autoimmune disease , present active autoimmune disease or inflammatory diseases Present or history of pulmonary diseases such as interstitial pneumonia, pneumoconiosis, drug-related pneumonia, pulmonary fibrosis, active pulmonary infection, severely impaired pulmonary function. Positive human immunodeficiency virus (HIV) test. Active hepatitis B or C, or tuberculosis. History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. History of gastrointestinal perforation and/or fistula at 6 months prior to study inclusion. Hydrothorax, ascites, and pericardial effusion with clinical symptoms requiring drainage. Known history of hypersensitivity to any components of the IBI389 or Sintilimab. Uncontrolled complications of disease. 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. Pregnant or nursing females.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI389<br>A dose escalation stage of IBI 389 monotherapy. | Drug: IBI 389 Injection<br>* IBI 389 IV Q2 Q3W Day 1<br>|
| Experimental: IBI 389 + sintilimab<br>A dose escalation stage of IBI 389 in combination with sintilimab. | Drug: IBI 308 injection<br>* IBI308 IV 200mg Q3W Day1<br>Drug: IBI 389 Injection<br>* IBI 389 IV Q2 Q3W Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with AEs and SAEs | To evaluate the safety and tolerability of IBI389 alone or in combination with Sintilimab [Adverse events (AEs), Serious Adverse Events (SAEs) ] | up to 2 years after enrollment | 
| Percentage of Participants with Dose-Limiting Toxicities (DLTs) | To evaluate the safety and tolerability of IBI389 alone or in combination with Sintilimab. | up to 28 Days following first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: AUC | The area under the curve (AUC) of serum concentration of the drug after the administration. | up to 2 years after enrollment | 
| Cmax | Maximum concentration (Cmax) of the drug after administration | up to 2 years after enrollment | 
| Immunogenicity: Percentage of ADA positive subjects | 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. | up to 2 years after enrollment | 
| Preliminary anti-tumor activity of IBI389 (Objective Response Rate) | Objective Response Rate (ORR) is the percentage of Complete Response (CR) plus partial response (PR) assessed by RECIST v1.1 criteria for solid tumors. | up to 2 years after enrollment |