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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: IBI 389 Injection; Drug: IBI 308 injection

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 Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: xiaoqin ruan; Phone Number: 18610683729; Email: xiaoqin.ruan@innoventbio.com

Study Locations

• China
  • Sichuan
    • Chendu, Sichuan, China, 610000
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: bi feng; Phone Number: 028-85422114; Email: bifeng@csco.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2022
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: November 25, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 20, 2021

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CIBI389A101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No