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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumors
• Interventions: Drug: IBI 389 Injection; Drug: IBI 308 injection

• Registration Number: NCT05164458
• Lead Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

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.

Study Timeline

• Study First Submitted: 2021-11-25
• Study First Submitted QC: 2021-12-06
• Study First Posted: 2021-12-20
• Study Start: 2022-03-22
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-27
• Last Update Posted: 2023-12-28
• Primary Completion: 2024-04-30
• Study Completion: 2024-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 320

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
IBI389	IBI 389 Injection	A dose escalation stage of IBI 389 monotherapy.
IBI 389 + sintilimab	IBI 308 injection	A dose escalation stage of IBI 389 in combination with sintilimab.
IBI 389 + sintilimab	IBI 389 Injection	A dose escalation stage of IBI 389 in combination with sintilimab.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

West China Hospital of Sichuan University; 🇨🇳 Chendu, Sichuan, China