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New treatment option for Locally Advanced Unresectable or Metastatic Solid Tumors
Official title A First-in-human Study of IBI343 in Subjects With Locally Advanced Unresectable or Metastatic Solid Tumors
ClinicalTrials.gov ID: NCT05458219
What this study is testing
What is IBI343?
IBI343 is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for locally advanced unresectable or metastatic solid tumors.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- 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...
- Age ≥ 18 years, of either sex.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
You likely can't join if
- Exclusion criteria common to Phases Ia and Ib:
- Is participating in another treatment clinical study other than an observational (non-treatment) clinical study or is in the survival follow-up phase...
- 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...
- Plans to receive other anti-tumor therapy during treatment with the study drug [palliative radiotherapy for symptomatic relief (e.g., pain) that does...
- 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...
- 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...
See the full eligibility criteria
Who can join
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- \ 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...
- 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...
- 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%...
- Participants with histopathologically confirmed metastatic PDAC who has not received previous systemic therapy in the metastatic setting. (For Safety Lead-in stage, participants who has received previous systemic...
- Participants must not have previously received anti-CLDN18.2 therapy.
- Participants must not have previously received topoisomerase inhibitor-based antibody-drug conjugate(s), unless given peri-operatively without evidence of resistance.
- \ CLDN18.2-positive confirmed by pathological examination by central laboratory (For Dose optimization stage, PDAC enrolled # specified expression of CLDN 18.2) for Phase Ib Cohort A:
- Histopathologically confirmed unresectable locally advanced or metastatic G/GEJ AC.
- Have received at least 2 lines of systemic therapy [anti-PD-(L)1 + platinum, fluoropyrimidines, paclitaxel/docetaxel, or irinotecan; participants with HER2 overexpression (defined as 3 + or 2 + by immunohistochemistry...
- High expression of \ \ CLDN18. 2 was confirmed by pathological examination. for Phase Ib Cohort B:
- Histopathologically confirmed unresectable locally advanced or metastatic G/GEJ AC.
- Disease progression after first-line standard therapy (HER2-overexpressing participants must have received prior anti-HER2 therapy unless contraindicated or justified non-benefit).
- Confirmed \ CLDN18.2-positive by histopathological examination. for Phase Ib Cohort C:
- Histopathologically confirmed unresectable locally advanced or metastatic PDAC.
- Disease progression after at least one prior systemic therapy. for Phase Ib Cohort D:
- Histopathologically confirmed unresectable locally advanced or metastatic BTC.
- Disease progression after at least one prior systemic therapy.
- Confirmed \ CLDN18.2-positive by histopathological examination. Notes:
- CLDN18.2-positive: defined as ≥ 1% of tumor cells with membranous staining of any intensity in tumor tissue by immunohistochemistry, when tested previously, at the study site, or at the central laboratory.
- High expression of CLDN18. 2: Claudin18.2 immunohistochemical membrane staining intensity ≥ 2 + in ≥ 75% of tumor cells.
- Moderate to high expression of CLDN18.2: Claudin18.2 immunohistochemical membrane staining intensity ≥ 2 + in ≥ 40% of tumor cells.
- Specified expression of CLDN18.2: Claudin18.2 immunohistochemical membrane staining intensity 1+/2+/3+ in ≥50% of tumor cells.
What rules you out
- Exclusion criteria common to Phases Ia and Ib:
- Is participating in another treatment clinical study other than an observational (non-treatment) clinical study or is in the survival follow-up phase of an treatment 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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
- Has a history of deep vein thrombosis, pulmonary embolism, or any other serious venous thromboembolism within 3 months prior to the first dose of study drug (implantable venous access port or catheter-derived...
- Has hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh B or more severe cirrhosis.
- Has complete or incomplete intestinal or bowel obstruction at the time of screening or a history of complete or incomplete intestinal or bowel obstruction within 3 months prior to first dose, or is at risk of intestinal...
- Has other acute or chronic disease or laboratory abnormality that may result in increased risk associated with study participation or study drug administration, or interfere with the interpretation of study results, and...
- Has a neurological or psychiatric illness or a social situation that affects compliance with study requirements, significantly increases the risk of AE, or affects the participant's ability to provide written ICF.
- Has a history of other primary malignancies, with the following exceptions:
- Curatively treated malignancy with no known active disease for ≥ 2 years prior to study enrollment and is at minimal risk of recurrence;
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease recurrence;
- Adequately treated carcinoma in situ with no evidence of disease recurrence.
- Has a known history of immunodeficiency.
- Has a history of allogeneic organ transplantation and history of allogeneic hematopoietic stem cell transplantation.
- Has a history of severe allergic reaction to other monoclonal antibodies and/or hypersensitivity to any of the formulation components of IBI343 or mFOLFOX or Irinotecan or liposomal Irinotecan (For phase 1a part 3 1L...
- Female participants who are pregnant or lactating.
- Has other conditions considered not eligible to participate in this study per the Investigator's judgement.
- Has known dihydropyrimidine dehydrogenase deficiency (DPD). (NOTE: Screening for DPD deficiency should be conducted per local requirements.)
- Has known peripheral sensory neuropathy \> grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
The study team makes the final eligibility decision.
Where it's taking place
- Austin, Texas, United States
- Irving, Texas, United States
- San Antonio, Texas, United States
- Darlinghurst, New South Wales, Australia
- Wollongong, New South Wales, Australia
- Benowa, Queensland, Australia
- Birtinya, Queensland, Australia
- Hefei, Anhui, China
- Wuhu, Anhui, China
- Beijing, Beijing Municipality, China
- Fuzhou, Fujian, China
- Guangzhou, Guangzhou, China
- Zhengzhou, Henan, China
- Wuhan, Hubei, China
- Changsha, Hunan, China
- Nanjing, Jiangsu, China
- Nanchang, Jiangxi, China
- Shenyang, Liaoning, China
- Yinchuan, Ningxia, China
- Xi'an, Shaanxi, China
+ 8 more site(s).
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Austin, Texas, United States; Irving, Texas, United States; San Antonio, Texas, United States; Darlinghurst, New South Wales, Australia; Wollongong, New South Wales, Australia; Benowa, Queensland, Australia and 22 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.