A First-in-human Study of IBI354 in Subjects with Locally Advanced Unresectable or Metastatic Solid Tumors

NCT ID: NCT05636215

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 368 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-04
• Study Completion Date: 2025-10-31

Brief Summary

This is a Phase 1/2, open-label, multicenter study designed to evaluate the safety, tolerability, and DLTs to establish the maximum tolerated dose (MTD) or maximum administered dose (MAD), and the RP2D of sequential doses of IBI354 (study drug), and to explore and confirm the efficacy, safety and tolerability of IBI354 in subjects with locally advanced unresectable or metastatic solid tumors.

Conditions

Locally Advanced Unresectable or Metastatic Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IBI354

Single arm

Group Type: EXPERIMENTAL

IBI354

Intervention Type: BIOLOGICAL

Recombinant Anti-HER2 monoclonal Antibody-Camptothecin derivative conjugate for injection

Interventions

IBI354

Recombinant Anti-HER2 monoclonal Antibody-Camptothecin derivative conjugate for injection

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Male or female subjects, ≥ 18 years

2. Phase 1a : Has a pathologically documented advanced/unresectable or metastatic solid tumor with HER2 alterations (IHC 1+, IHC 2+, IHC 3+ and/or ISH+ and/or NGS confirmed mutant or amplification).

Phase 1b/2: Selected solid tumors enrolled Subjects with advanced GC/BC/BTC/CRC/Gyn with her2 expression (IHC 1+, IHC 2+, IHC 3+ and/or ISH+).

3. Adequate bone marrow and organ function

4. Subjects, both male and female, who are either not of childbearing potential or who agree to use at least one highly effective method of contraception during the study (begin from screening or within 2 weeks prior to the first dose, whichever comes first, and continue until 6 months after the last dose of study drug); Subjects, both male and female, who are either not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug

5. Subjects with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol;

6. Have LVEF ≥ 50% by echocardiography (ECHO) within 28 days before study drug administration.

Exclusion Criteria

1. Received previous anti-tumor therapy within 4 weeks or 5 half-lives of the anti-tumor regimens before the first administration of study drug, whichever is shorter;

2. Plan to receive other antitumor therapy during the study excluding palliative radiotherapy for the purpose of symptom (like pain) relief that must also do not have impact on tumor assessment throughout the study;

3. Potent cytochrome P450 3A4 (CYP3A4) inhibitors within 2 weeks or 5 half-lives (whichever is longer) before first administration of the study drug.

4. Has adverse reactions resulting from previous antitumor therapies, which have not resolved to Grade 0 or 1 toxicity according to NCI-CTCAE v5.0 (except for alopecia, fatigue, pigmentation and other conditions with no safety risk according to investigators' opinion) or baseline prior to first administration of the study drug;

5. Known symptomatic central nervous system (CNS) metastases.

6. History of pneumonia requiring corticosteroids therapy, or history of clinically significant lung diseases or who are suspected to have these diseases by imaging at screening period;

7. Uncontrolled diseases including:

• Uncontrolled infection requiring systematic antibiotics, antivirals or antifungals within 2 weeks prior to first administration of the study drug;
• Known human immunodeficiency virus (HIV) infection, or HIV positive (HIV 1/2 Ab positive);
• HBsAg positive and/or HBcAb positive with HBV DNA titer ≥ 104 copies/mL or ≥ 2000 IU/mL or higher than lower limit of detection or HCV Ab positive with HCV RNA>103 copies/mL;
• Active infection with COVID-19;
• Active tuberculosis infection, or still on anti-tuberculosis therapy or received anti-tuberculosis therapy within 1 year prior to first administration of the study drug;
• Active syphilis infection or latent syphilis requiring treatment;
• Symptomatic congestive heart failure Grade II-IV, symptomatic or uncontrolled arrhythmias, QTc interval > 480 ms or personal or family history of congenital long/short QT syndrome;
• SBP ≥ 160mmHg or DBP ≥ 100mmHg;

8. History of any arterial thromboembolic event within 6 months prior to the first administration of study drug, including myocardial infarction, unstable angina pectoris, cerebrovascular stroke or transient ischemic attack, etc.;

9. Risk of intestinal obstruction or perforation (including but not limited to: acute diverticulitis, abdominal abscess, etc.) or a history of inflammatory bowel disease, Crohn's disease, ulcerative colitis, or chronic diarrhea;

10. Do not have adequate treatment washout period before study drug administration, defined as:

• Major surgery; ≥ 4 weeks.
• Radiation therapy；≥ 4 weeks (if palliative stereotactic radiation therapy, ≥ 2 weeks).
• Autologous transplantation；≥ 3 months.
• Hormonal therapy；≥ 2 weeks.
• Chemotherapy (including antibody drug therapy or other antitumor therapy)； ≥ 3 weeks.
• Immunotherapy； ≥ 4 weeks.
• Cytochrome P450 (CYP) 3A4 strong inhibitor；≥ 3 elimination half-lives of the inhibitor.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innovent Biologics (Suzhou) Co. Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Scientia Clinical Research Ltd

Randwick, New South Wales, Australia

Site Status: COMPLETED

Westmead Hospital

Sydney, New South Wales, Australia

Site Status: COMPLETED

Sunshine Coast University Private Hospital

Sunshine Coast, Queensland, Australia

Site Status: COMPLETED

Monash Health

Clayton, Victoria, Australia

Site Status: COMPLETED

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Affiliated Cancer Hospital of Chongqing University

Chongqing, Chongqing Municipality, China

Site Status: RECRUITING

Countries

Australia; China

Central Contacts

yuan lei

Role: CONTACT

yuan.lei@innoventbio.com

8610-68585566

Facility Contacts

Shen Lin

Role: primary

doctorshenlin@sina.cn

010-88196090

Zhou Qi

Role: primary

qizhou9128@163.com

023-65311341

Other Identifiers

CIBI354A101

Identifier Type: -

Identifier Source: org_study_id