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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05164458
• Other study ID #: CIBI389A101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 22, 2022
• Est. completion date: September 30, 2024

Study information

• Verified date: December 2023
• Source: Innovent Biologics (Suzhou) Co. Ltd.
• Contact: xiaoqin ruan
• Phone: 18610683729
• Email: xiaoqin.ruan[@]innoventbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: September 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• IBI 308 injection
IBI308 IV 200mg Q3W Day1
• IBI 389 Injection
IBI 389 IV Q2~Q3W Day 1

Locations

Country	Name	City	State
China	West China Hospital of Sichuan University	Chendu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Innovent Biologics (Suzhou) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Pharmacokinetics: AUC	The area under the curve (AUC) of serum concentration of the drug after the administration.	up to 2 years after enrollment
Secondary	Cmax	Maximum concentration (Cmax) of the drug after administration	up to 2 years after enrollment
Secondary	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
Secondary	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