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

Recruiting now · Phase 1

Conditions studied: Locally Advanced Unresectable or Metastatic Solid Tumors

In brief

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.

Key facts

Study ID

NCT05458219

Run by

Innovent Biologics (Suzhou) Co. Ltd.

People needed

470

Starts

2022-10-26

Expected to finish

2027-12-31

Last updated by the study team

2026-05-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Inclusion criteria to be met for both Phase Ia and Phase Ib:
• 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.
• Inclusion Criteria for Phase Ia Dose Escalation:
• 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.
• Inclusion Criteria for Phase Ia Dose Expansion, Dose Optimization :
• 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.
• Inclusion Criteria for Phase Ia Part 3 1L G/GEJ AC Cohort:
• 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.
• Confirmed Her 2-negative (defined as IHC 0 or 1+, or IHC 2+ and negative by in situ hybridization) disease.
• Confirmed combined positive score (CPS) <5 as determined by local IHC testing.
• Participants must not have previously received topoisomerase inhibitor-based antibody-drug conjugate(s), unless given peri-operatively without evidence of resistance.
• Participants must not have previously received anti-CLDN18.2 therapy.
• *CLDN18.2-positive confirmed by pathological examination by central laboratory (For Dose optimization stage, G/GEJ AC enrolled participants with Claudin18.2 immunohistochemical membrane staining intensity 2+/3+ in ≥50% of tumor cells).
• Inclusion Criteria for Phase Ia Part 3 1L PDAC Cohort:

You may not qualify if…

• Exclusion criteria common to Phases Ia and Ib:
• 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.
• Has active syphilis or latent syphilis requiring treatment.
• Has symptomatic congestive heart failure (New York Heart Association classification NYHA class II-IV), symptomatic or uncontrolled arrhythmia, QTc interval > 480 ms, or personal or family history of congenital long/short QT syndrome.
• For part 3 1L G/GEJ AC and 1L PDAC cohort, the QTc should be calculated based on the average of triplicate screening ECG (using Appendix 4 Calculation Formula of QTcF)
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) by standard treatment.
• Has one or more arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, etc., within 6 months prior to the first dose of study drug.
• Has received stent implantation in tracheal or digestive tract.
• Has symptomatic pleural, ascites, or pericardial effusion requiring intervention (e.g., drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy [CART]). Asymptomatic participants with a small amount of pleural effusion, ascites or pericardial effusion on imaging are allowed. (Drainage and CART are not allowed within 2 weeks prior to screening assessment).
• Has esophageal or gastric varices that require immediate intervention (e.g., ligature or sclerotherapy) or are considered to be at high risk for bleeding in the opinion of the investigator or consulting gastroenterologist or hepatologist. Participants with evidence of portal hypertension (including splenomegaly on imaging) or a history of prior variceal bleeding must undergo endoscopic evaluation within 3 months prior to the first dose of study drug.
• Has one or more life-threatening bleeding event or Grade 3 or 4 gastrointestinal/variceal bleeding requiring blood transfusion, endoscopic or surgical treatment within 3 months prior to the first dose of study drug

Where it is running

• Ningbo Medical Center Li Huili Hospital — Ningbo, Zhejiang, China (enrolling)
• Next Oncology-Dallas — Irving, Texas, United States (enrolling)
• Next Oncology-San Antonio — San Antonio, Texas, United States (enrolling)
• St Vincent's Hospital Sydney — Darlinghurst, New South Wales, Australia (enrolling)
• Cancer Care Wollongong — Wollongong, New South Wales, Australia (enrolling)
• Next Oncology-Austin — Austin, Texas, United States (enrolling)
• Sunshine Coast University Private Hospital — Birtinya, Queensland, Australia (enrolling)
• Anhui Cancer Hospital — Hefei, Anhui, China (enrolling)
• Anhui Provincial Hospital — Hefei, Anhui, China (enrolling)
• The First Affiliated Hospital of Wannan Medical College — Wuhu, Anhui, China (enrolling)
• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (enrolling)
• Tumor Hospital, Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (enrolling)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (enrolling)
• Sun Yat-sen Memorial Hospital Sun Yat-Sen university — Guangzhou, Guangzhou, China (enrolling)
• The First Affiliated Hospital of Sun Yat-sen University — Guangzhou, Guangzhou, China (enrolling)
• Henan Provincial People&#39;s Hospital — Zhengzhou, Henan, China (enrolling)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (enrolling)
• Hubei Cancer Hospital — Wuhan, Hubei, China (enrolling)
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technolog — Wuhan, Hubei, China (enrolling)
• Hunan Cancer Hospital — Changsha, Hunan, China (enrolling)
• Nanjing Drum Tower Hospital — Nanjing, Jiangsu, China (enrolling)
• Jiangxi Cancer Hospital — Nanchang, Jiangxi, China (enrolling)
• The Second Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (enrolling)
• The First Hospital of China Medical University — Shenyang, Liaoning, China (enrolling)
• Ningxia Medical University General Hospital — Yinchuan, Ningxia, China (enrolling)

Full record on ClinicalTrials.gov

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