A First-in-human Study of IBI343 in Subjects With Locally Advanced Unresectable or Metastatic Solid Tumors

NCT05458219 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CIBI343A101
• Study Type: interventional
• Target: 470
• Locations: 3 countries
• Sites: 39

Brief Summary

This is a Phase Ia/Ib, multicenter, open-label, first-in-human study to evaluate the safety, tolerability, PK, and efficacy of IBI343 in participants with locally advanced unresectable or metastatic solid tumors. It is planned to be carried out in different countries or regions such as China, Australia and US. There are three parts in phase Ia. Part 1 includes dose escalation and expansion phase and part 2 is designed for dose optimization for IBI343 monotherapy. Part 3 1L G/GEJ AC and 1L PDAC cohorts will include an initial safety lead-in stage to confirm the tolerability of IBI343 in combination with chemotherapy in 1L PDAC and G/GEJ AC, followed by a randomized dose-optimization stage designed to further characterize safety, pharmacokinetics, and preliminary efficacy to inform selection of the recommended Phase 3 dose.

Conditions

Locally Advanced Unresectable or Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (17)

• Adverse events(AEs), treatment emergent adverse event (TEAEs)，serious adverse events (SAEs)

  Adverse events will be assessed by investigator(s) according to NCI-CTCAE v5.0.

  Up to 90 days after the last administration

• Dose-limiting Toxicity (DLT)

  DLTs are assessed during the DLT observation period to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

  21 days after the first dose of IBI343

• To determine RP2D of IBI343.

  To determine RP2D of IBI343.

  Up to 2 years

• ORR assessed by the investigator based on RECIST version 1.1.

  ORR assessed by the investigator based on RECIST version 1.1.ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR)

  Up to 2 years

• Number of subjects with clinically significant changes in physical examination results

  A complete physical examination will include: general appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose, and pharynx), lymph nodes, thyroid, musculoskeletal (including spine and extremities), genital/anal, and neurological assessments, if indicated. Clinically significant abnormal findings at screening will be recorded as medical history or AE based on the investigator's analysis and judgment.

  Up to 2 years

• Number of participants with abnormal vital signs

  Collection of vital signs will include temperature in ℃, measurement tool is physiological parameter

  Through study completion, up to 2 years

• Objective response rate (ORR)

  Through study completion, up to 2 years

  ORR is defined as the proportion of participants with a completeresponse (CR) or partial response (PR)

• Number of participants with abnormal laboratory tests results

  Blood routine：RBC, HGB, HCT, WBC, PLT, LYM, ANC

  Through study completion, up to 2 years

• Number of participants with abnormal vital signs

  Collection of vital signs will include pulse in beats per minute. measurement tool is physiological parameter

  Through study completion, up to 2 years

• Number of participants with abnormal vital signs

  Collection of vital signs will include respiratory rate in times/min. measurement tool is physiological parameter

  Through study completion, up to 2 years

• Number of participants with abnormal vital signs

  Collection of vital signs will include blood pressure in kPa. measurement tool is physiological parameter

  Through study completion, up to 2 years

• Number of participants with abnormal laboratory tests results

  Blood biochemistry: TBIL, DBIL, ALT, AST, γ-GGT, ALP, ALB, TP, LDH, Urea or BUN, Cr, Na, K, Cl, Mg, Ca, P, Amylase, Lipase and FBG

  Through study completion, up to 2 years

• Number of participants with abnormal laboratory tests results

  Urinalysis: PH, Specific Gravity, UWBC, UPRO, URBC, UGLU, UBLD

  Through study completion, up to 2 years

• Number of participants with abnormal laboratory tests results

  Coagulation function: APTT, PT, INR, Fbg, D-dimer

  Through study completion, up to 2 years

• Number of participants with abnormal laboratory tests results

  Viral serology test: HBsAg, HBsAb, HBcAb, HBeAg, HBeAb, HBV DNA, HCV antibody, HCV RNA, HIV antibody, Treponema pallidum-specific antibody

  Through study completion, up to 2 years

• Number of participants with abnormal laboratory tests results

  Myocardial injury markers: CK, CK-MB, Troponin I or T, BNP or NT-proBNP

  Through study completion, up to 2 years

• Number of participants with abnormal laboratory tests results

  Fecal analysis: occult blood (OB)

  Through study completion, up to 2 years

Secondary Outcomes (16)

• maximum concentration (Cmax)

  Up to 2 years

• area under the curve (AUC)

  Up to 2 years

• clearance rate (CL)

  Up to 2 years

• half-life (t1/2)

  Up to 2 years

• Anti-drug antibody(ADA) of IBI343

  Up to 2 years

Study Arms (2)

3 arms

EXPERIMENTAL

Phase 1a Part 3: For monotherapy: 6 mg/kg Q3W was confirmed as the optimal dosing regimen for balancing clinical benefits and potential risks. In 1L G/GEJ AC and 1L PDAC cohort of the Phase Ia (Part 3) study, IBI343 combination therapy is proposed to be administered at doses of 4 mg/kg (Dose level 1) Q2W or 5 mg/kg (Dose level 2) Q2W in participants with G/GEJ AC and PDAC for the randomized study.

Drug: FOLFIRINOX/mFOLFIRINOX; Drug: mFOLFOX; Drug: IBI343

Single arm

EXPERIMENTAL

Phase 1a Part 1 Dose Escalation: IBI343 will be administered intravenously (IV) at different dose levels following traditional 3+3 dose escalation design for following levels. Phase 1a Part 1 Dose Expansion: IBI343 will be administered at dose levels which is equal or lower than MTD. Each dose level contains no more than 30 subjects (including subjects in dose escalation) Phase 1a Part 2 Dose Optimization: IBI343 will be administered in parallel cohorts (randomized 1:1 ratio) to determine the optimal dose for the PDAC indication across China, Australia and the US (n=40). Dose levels 4.5mg/kg and 6mg/kg will be studied. Phase 1b Dose Extension: IBI343 will be administered at RP2D.

Drug: IBI343

Interventions

IBI343 DRUG

IBI343 will be administered intravenously (IV) on Day 1 of every 21-day cycle.

Single arm

FOLFIRINOX/mFOLFIRINOX DRUG

FOLFIRINOX/mFOLFIRINOX will be administered IV Q2W on Days 1-3 every 2 weeks (14 days).

3 arms

mFOLFOX DRUG

mFOLFOX will be administered IV Q2W on Days 1-3 every 2 weeks (14 days) in each cycle after IBI343

3 arms

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has signed written Informed Consent Form (ICF), willing and able to comply with protocol-specified visits and related procedures.
• Phase Ia dose escalation phase, Phase Ia part 3 1L G/GEJ AC and 1L PDAC cohorts Safety Lead-in stage: Has at least 1 evaluable lesion according to RECIST v1.1; Phase Ia dose expansion and dose optimization phase, Phase Ia part 3 1L G/GEJ AC and 1L PDAC cohorts Dose optimization stage, Phase Ib: Has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors RECIST v1.1.
• Age ≥ 18 years, of either sex.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Has an expected survival ≥ 12 weeks.
• Has adequate bone marrow and organ function. Defined as:
• Hematology: ANC ≥ 1.5 × 109/L; Platelet count ≥ 100 × 109/L; Hemoglobin ≥ 9.0 g/dL, participants must not have received transfusion of blood products (including red blood cell suspension, apheresis platelets, cryoprecipitate, etc.), erythropoietin (EPO), G-colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) within 7 days prior to blood sample collection;
• Hepatic function: TBIL ≤ 1.5 × ULN (TBIL ≤ 3 × ULN is allowed for participants with Gilbert's syndrome); ALT and AST ≤ 2.5 × ULN for participants without liver metastasis and ≤ 5 × ULN for participants with liver metastasis; Albumin ≥ 28 g/L;
• Renal function: estimated creatinine clearance ≥ 30mL/min (using Appendix 5. Calculation of Estimated Creatinine Clearance and Body Surface ).
• Coagulation function: international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (participants receiving anticoagulant therapy with coagulation function within the above range are allowed).
• Female participants of childbearing potential or male participants whose partners are female of childbearing potential are required to use effective contraceptive measures throughout the treatment period and for 6 months after the final treatment period.
• Participants with histopathologically confirmed unresectable locally advanced or metastatic malignant solid tumors that have failed or were intolerant to standard therapy or for whom no standard therapy is available.
• Participants with histopathologically confirmed unresectable locally advanced or metastatic G/GEJ AC, PDAC, BTC, or other solid tumors who have failed or were intolerant to standard therapy or for which no standard therapy is available.
• \* CLDN18.2-positive confirmed by pathological examination (in dose expansion phase, G/GEJ AC and PDAC preferentially enrolled \*\*\* moderate to high expression of CLDN18. 2; in dose optimization phase , G/GEJ AC preferentially enrolled \*\*high expression of CLDN18.2 and PDAC preferentially enrolled \*\*\*moderate to high expression of CLDN18.2). For participants with previous anti-CLDN18.2 treatment (including but not limited to monoclonal antibodies, ADCs, CAR-T, etc.), tumor samples should be obtained post anti-CLDN18.2 therapy for CLDN18.2 expression evaluation.
• Participants with histopathologically confirmed unresectable locally advanced or metastatic G/GEJ AC who has not received previous systemic therapy. (For Safety Lead-in stage, participants who has received previous systemic therapy are permitted.) A prior (neo)adjuvant systemic therapy completed within 6 months prior to disease relapse or progression will be considered as having received previous systemic therapy.

You may not qualify if:

• Is participating in another interventional clinical study other than an observational (non-interventional) clinical study or is in the survival follow-up phase of an interventional study.
• Has received the last dose of antineoplastic therapy within 4 weeks or 5 half-lives of an antineoplastic therapy (whichever is shorter) prior to the first dose of study drug.
• Plans to receive other anti-tumor therapy during treatment with the study drug \[palliative radiotherapy for symptomatic relief (e.g., pain) that does not affect response assessment is allowed\].
• Has received a strong cytochrome P450 3A4 (CYP3A4) inhibitor within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of study drug.
• Toxicities due to prior therapy that have not recovered to Grade 0 or 1 per NCI CTCAE v5.0 prior to the first dose of study drug (excluding alopecia, asthenia, hyperpigmentation, and other conditions with no safety risk per the judgment of the investigator).
• Has undergone major surgical procedure (craniotomy, thoracotomy, laparotomy or others per the investigator, excluding needle biopsy) or has unhealed wounds, ulcers, or bone fracture within 4 weeks prior to the first dose of study drug; Or plans to undergo major surgery during the study period; Note: Local surgical treatment of isolated lesions for palliative purposes is acceptable.
• Has gastric pyloric obstruction and/or persistent recurrent vomiting (≥ 3 episodes in 24 hours).
• Has a history of gastrointestinal perforation and/or fistula within 6 months that has not resolved surgically prior to the first dose of study drug.
• Has symptomatic central nervous system metastases. Participants with asymptomatic brain metastases (i.e., no neurological symptoms, no need for glucocorticoid treatment, all brain metastasis ≤ 1. 5 cm) or stable symptoms after treatment of brain metastases must meet all of the following criteria to participate in the study: no metastasis in the midbrain, pons, cerebellum, meninges, medulla oblongata or spinal cord; Stable clinical status for at least 4 weeks with definitive clinical evidence of no new or enlarging brain metastasis and discontinuation of corticosteroids and anticonvulsants for at least 2 weeks prior to the first dose of study drug. Note: lesions of the central nervous system will not be considered as a target lesion
• Has a history of pneumonitis requiring corticosteroids therapy, or a history of interstitial lung disease, non-infectious pneumonitis, severely impaired lung function or uncontrolled lung disease, such as pulmonary fibrosis, severe radiation pneumonitis, acute lung injury, or suspected of having the above diseases during the screening period.
• Has uncontrolled medical conditions, such as:
• Active or clinically uncontrolled serious infection requiring treatment with systemic anti-infectives (antibiotics, antivirals, or antifungals) within 1 week prior to the first dose of study drug, including but not limited to the infection of respiratory tract, urinary system, biliary tract infection, etc.
• Participants infected with human immunodeficiency virus (HIV) (HIV 1/2 antibody positive).
• Acute or chronic active hepatitis B (defined as hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody positive (HBcAb) with hepatitis B virus DNA copies ≥ 104 copies/mL or ≥ 2000 IU/mL or above the lower limit of detection) or acute or chronic active hepatitis C \[hepatitis C virus antibody (HCVAb) positive with HCV RNA \> 103 copies/mL\]. Participants whose test results are below the above criteria after receiving antiviral therapy with nucleotides, or participants with positive serology but negative HCV-RNA test result are eligible.
• Has active pulmonary tuberculosis, is being treated with anti-tuberculosis therapy or having received anti-tuberculosis therapy within 1 year prior to the first dose of study drug.

Sponsors & Collaborators

• TigerMed: collaborator
• Innovent Biologics (Suzhou) Co. Ltd.: lead
• Fortvita Biologics (USA)Inc.: collaborator

Study Sites (39)

Next Oncology-Austin

Austin, Texas, 78758, United States

RECRUITING

Next Oncology-Dallas

Irving, Texas, 75039, United States

RECRUITING

Next Oncology-San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Cancer Care Wollongong

Wollongong, New South Wales, 2500, Australia

RECRUITING

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

ACTIVE NOT RECRUITING

Sunshine Coast University Private Hospital

Birtinya, Queensland, 4575, Australia

RECRUITING

Anhui Cancer Hospital

Hefei, Anhui, China

RECRUITING

Anhui Provincial Hospital

Hefei, Anhui, China

RECRUITING

The First Affiliated Hospital of Wannan Medical College

Wuhu, Anhui, China

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

RECRUITING

Tumor Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, China

RECRUITING

Sun Yat-sen Memorial Hospital Sun Yat-Sen university

Guangzhou, Guangzhou, China

RECRUITING

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangzhou, China

RECRUITING

Henan Provincial People's Hospital

Zhengzhou, Henan, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

RECRUITING

Hubei Cancer Hospital

Wuhan, Hubei, China

RECRUITING

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technolog

Wuhan, Hubei, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

RECRUITING

Jiangxi Cancer Hospital

Nanchang, Jiangxi, China

RECRUITING

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, China

RECRUITING

Ningxia Medical University General Hospital

Yinchuan, Ningxia, China

RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

RECRUITING

Jinan Central Hospital

Jinan, Shandong, China

RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, China

RECRUITING

Jining First People's Hospital

Jining, Shandong, China

RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

RECRUITING

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

RECRUITING

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, China

RECRUITING

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, China

RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

RECRUITING

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

RECRUITING

Ningbo Medical Center Li Huili Hospital

Ningbo, Zhejiang, China

RECRUITING

Related Publications (1)

• Liu J, Yang J, Sun Y, Gong J, Yue J, Pan Y, Sun M, Song R, Xiao X, Tazbirkova A, Ruan J, Liu Z, Liu Z, Li Z, Sheng L, Qin Y, Ying J, Yu X, Zhang J, Mou Y, Lu C, Chen P, Li S, Li J, Qu X, Deng T, Du J, Zhou A, Li E, Yuan X, Liang X, Yu W, Morris M, Luo Y, Zhao X, Guo Y, Zhou H, Shen L. CLDN18.2-targeting antibody-drug conjugate IBI343 in advanced gastric or gastroesophageal junction adenocarcinoma: a phase 1 trial. Nat Med. 2025 Sep;31(9):3028-3036. doi: 10.1038/s41591-025-03783-8. Epub 2025 Jul 16.

  PMID: 40670773 DERIVED

MeSH Terms

Interventions

folfirinox

Central Study Contacts

Suhua Dong

CONTACT

0512-69566088; suhua.dong@innoventbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 14, 2022
• Study Start: October 26, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); AU (4); CN (32)