Trial Title:
Study of IBI343 in Subjects With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma
NCT ID:
NCT06321913
Condition:
Advanced Gastric/Gastroesophageal Junction Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Esophageal Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IBI343 combined with IBI308
Description:
IBI343 Specifications: 100 mg/bottle Approval method: TBD Q3W intravenous infusion (IV)
sintilimab Specifications: 100mg (10ml)/bottle Afghan way: 200 mg Q3W IV infusion
Arm group label:
IBI343
Summary:
The goal of this clinical trial] is toevaluate the safety, tolerability and efficacy of
IBI343 combined with sintilimab in the treatment of subjects with advanced
gastric/gastroesophageal junction adenocarcinoma. The main aim is to evaluate the
efficacy and safety of IBI343 combination treatment in subjects with advanced
gastric/gastroesophageal junction adenocarcinoma.The secondary aim is to evaluate other
efficacy endpoints in subjects with IBI343 combination therapy for advanced
gastric/gastroesophageal junction adenocarcinoma.The exploratory purpose is to evaluate
the correlation between CLDN18.2 expression levels in tumor tissues and the efficacy of
IBI343 combination therapy.
Participants will be asked to enroll about 3-12 patients in the safety introduction
period.，and about 25 patients are planned to be enrolled in the POC phase.
Detailed description:
The goal of this clinical trial] is toevaluate the safety, tolerability and efficacy of
IBI343 combined with sintilimab in the treatment of subjects with advanced
gastric/gastroesophageal junction adenocarcinoma. The main aim is to evaluate the
efficacy and safety of IBI343 combination treatment in subjects with advanced
gastric/gastroesophageal junction adenocarcinoma.The secondary aim is to evaluate other
efficacy endpoints in subjects with IBI343 combination therapy for advanced
gastric/gastroesophageal junction adenocarcinoma.
Participants will be asked to enroll about 3-12 patients in the safety introduction
period.，and about 25 patients are planned to be enrolled in the POC phase.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Sign the written informed consent form (ICF) and be willing and able to comply with
the visits and related procedures stipulated in the plan.
2. Histopathologically confirmed unresectable locally advanced, recurrent or metastatic
G/GEJ AC.
3. Part 1: Previously received first-line platinum + fluorouracil + taxane systemic
treatment failure or intolerance; Part 2: Previous first-line systemic standard
treatment failure or intolerance.
4. According to the Response Evaluation Criteria for Solid Tumors RECIST v1.1, there is
at least 1 measurable lesion (no previous radiotherapy). (Accurate measurement at
baseline by computed tomography (CT) or magnetic resonance imaging (MRI)
(intravenous contrast agent is preferred) shows that its long diameter is ≥10 mm
(except for lymph nodes, the short axis of the lymph node must be ≥ 15 mm), the
target lesion diameter is ≥2 times the imaging slice thickness and the lesion is
suitable for repeated and accurate measurement. If a lesion located in a previously
irradiated area clearly demonstrates progression that meets the RECIST V1.1
criteria, the lesion can be regarded as a measurable lesion) .
5. Age ≥18 years old, no gender limit.
6. According to the Eastern Cooperative Oncology Group Performance Status (ECOG PS)
score of 0 or 1.
7. Expected survival ≥12 weeks.
8. Have adequate bone marrow and organ function:
1. Blood routine: ANC ≥ 1.5 × 109/L; platelet count ≥ 100 × 109/L; hemoglobin
content ≥ 9.0 g/dL. Subjects must not have received blood products (including
red suspension) within 7 days before collecting blood samples. , platelet
apheresis, cryoprecipitate, etc.), erythropoietin (EPO), G-colony stimulating
factor (Granulocyte-Colony Stimulating Factor, G-CSF) or granulocyte-macrophage
colony-stimulating factor (Granulocyte-Macrophage Colony-Stimulating Factor,
GM-CSF) treatment;
2. Liver function: TBIL≤1.5×ULN (TBIL≤3×ULN is allowed for subjects with Gilbert
syndrome); ALT and AST for subjects without liver metastasis ≤2.5×ULN, ALT and
AST for subjects with liver metastasis ≤5×ULN; albumin ≥28 g/L;
3. Renal function: creatinine clearance ≥60 mL/min (using Cockcroft-Gault
formula); urinary protein <2+ or 24h total urinary protein <1 g;
4. Coagulation function: International Normalized Ratio (INR) ≤ 1.5 and Activated
Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN (anticoagulant therapy is
allowed and the coagulation function is within the above range) subjects).
9. Female subjects of childbearing age or male subjects whose partners are women of
childbearing age must take effective contraceptive measures during the entire
treatment period and within 6 months after the treatment period.
10. The pathological tissue test confirmed that *CLDN18.2 was positive.
11. CPS≥1.
Exclusion Criteria:
1. Are participating in another interventional clinical study, excluding observational
(non-interventional) clinical studies or in the survival follow-up phase of an
interventional study.
2. Receive treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor within 2
weeks or 5 half-lives (whichever is longer) before the first dose of the study drug.
3. Receive the last anti-tumor treatment 4 weeks before the first administration of the
study drug or within 5 half-lives of the anti-tumor treatment drug (whichever is
shorter).
4. Received therapeutic or palliative radiotherapy within 2 weeks before the first
administration of the study drug.
5. Receive biliary stent implantation within 7 days before taking the study drug for
the first time.
6. Plan to receive other anti-tumor treatments during the period of drug treatment in
this study [Palliative radiotherapy is allowed for the purpose of relieving symptoms
(such as pain) and does not affect the evaluation of efficacy].
7. Any live vaccine within 4 weeks before the first dose of study drug or planned
during the study.
8. Have undergone major surgical surgery (craniotomy, thoracotomy or laparotomy or
other defined by the investigator, excluding needle biopsy) or have unhealed wounds,
ulcers or fractures within 4 weeks before the first administration of the study drug
; or plan to have major surgery during the study period. For palliative purposes,
local surgical treatment of isolated lesions is acceptable.
9. There are toxicities caused by previous treatment that have not recovered to NCI
CTCAE v5.0 grade 0 or 1 before the first administration of the study drug (excluding
alopecia, fatigue, pigmentation and other toxicities that are not considered to be
safety risks according to the investigator's judgment) Condition).
10. Have a history of gastrointestinal perforation and/or fistula within 6 months before
the first administration of the study drug, which has not been cured after surgical
treatment.
11. Presence of pyloric obstruction and/or persistent and repeated vomiting (vomiting ≥
3 times within 24 hours).
12. Digestive tract [refers to the muscular tube from the mouth to the anal canal,
including the oral cavity, pharynx, esophagus, stomach, small intestine (duodenum,
jejunum, ileum), large intestine (cecum, appendix, colon, rectum) and anal canal
etc.] or after endotracheal stent implantation.
13. Symptomatic central nervous system metastases. Subjects with asymptomatic brain
metastases (i.e., no neurological symptoms, no need for glucocorticoid treatment,
and brain metastases ≤1.5 cm) or subjects with stable symptoms after treatment of
brain metastases need to meet all the following criteria to participate This study:
No midbrain, pontine, cerebellar, meningeal, medulla or spinal cord metastases;
clinical status remains stable for at least 4 weeks, clinical evidence confirms no
new or expanding brain metastases, and corticosteroids are discontinued before the
first dose of study drug and anticonvulsant medication for at least 2 weeks. Note:
The central nervous system is not a target lesion.
14. Bone metastasis with risk of paraplegia.
15. Interstitial lung disease that requires steroid treatment, or a history of
interstitial lung disease, non-infectious pneumonia, severely impaired lung function
or uncontrolled lung disease, such as pulmonary fibrosis, severe radiation
pneumonitis, acute lung disease Injury, etc., or suspected to have the above
diseases during screening.
16. There are uncontrolled diseases, such as:
1. There is an infection that is poorly controlled and requires treatment with
systemic anti-infective drugs (antibiotics, antiviral drugs or antifungal
drugs) within one week before the first administration of the study drug.
2. People infected with human immunodeficiency virus (HIV) (HIV 1/2 antibody
positive).
3. Acute or chronic active hepatitis B (defined as hepatitis B surface Antigen
(HBsAg) and/or hepatitis B core antibody (Hepatitis B Core Antibody, HBcAb)
positive and hepatitis B virus DNA copies Number ≥ 104 copies/mL or ≥ 2000
IU/mL or acute or chronic active hepatitis C [Hepatitis C Virus antibody
(HCVAb) positive, HCV RNA > 103 copies/mL]. After nucleotide antiviral
treatment, low Subjects who meet the above criteria, as well as HCV
antibody-positive but RNA-negative subjects are allowed to enroll.
4. Active COVID-19 infection.
5. Active pulmonary tuberculosis, currently receiving anti-tuberculosis treatment
or receiving anti-tuberculosis treatment within 1 year before the first
administration of the study drug.
6. Active syphilis or latent syphilis requires treatment.
7. Individuals with symptomatic congestive heart failure (New York Heart
Association Class II~IV), symptomatic or poorly controlled arrhythmias, QTc
interval >480 ms or congenital long/short QT syndrome or Family history.
8. Standardize treatment for poorly controlled hypertension (systolic blood
pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg).
9. The tumor invades or compresses surrounding important structures (such as large
blood vessels, trachea, etc.) or there is a risk of
gastrointestinal/respiratory fistula.
10. Pleural effusion, ascites, or pericardial effusion that is symptomatic and
requires intervention (eg, drainage).
11. Esophageal or gastric varices requiring immediate intervention (e.g., banding
or sclerotherapy) or deemed to be at higher risk for bleeding based on the
opinion of the investigator or in consultation with a gastroenterologist or
hepatologist, with evidence of portal hypertension (including Subjects with
splenomegaly on imaging studies) or a previous history of variceal bleeding
must undergo endoscopic evaluation within 3 months before the first dose of
study drug.
12. Any life-threatening bleeding event or grade 3 or 4 gastrointestinal/variceal
bleeding event requiring transfusion, endoscopic or surgical treatment within 3
months before the first dose of study drug.
13. Any arterial thromboembolic events within 6 months before the first
administration of the study drug, including myocardial infarction, unstable
angina, cerebrovascular accident, transient ischemic attack, etc.
14. History of new or uncontrolled deep vein thrombosis, pulmonary embolism, or any
other severe venous thromboembolism (implantable venous port or
catheter-derived thrombosis, or Superficial venous thrombosis is not considered
a "severe" venous thromboembolism).
15. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or more
severe cirrhosis.
16. Risk of intestinal obstruction or intestinal perforation (including but not
limited to acute diverticulitis, history of abdominal abscess) or history of
the following diseases: inflammatory bowel disease or extensive bowel resection
(partial colectomy or extensive small bowel resection, complicated by chronic
diarrhea), Crohn's disease, ulcerative colitis, etc.
17. Significant malnutrition (if intravenous nutritional supplement is required,
the weight has dropped by 5% within 1 month since the signing of the informed
consent form, or the weight has dropped by more than 15% within 3 months, or
the food intake has been reduced by 1/2 or more within 1 week) . Exceptions
will be made if malnutrition has been corrected for more than 4 weeks before
the first administration of the study drug.
18. Other acute or chronic conditions or laboratory abnormalities that may increase
the risks associated with study participation or administration of study drugs,
or interfere with the interpretation of study results, and which, in the
investigator's discretion, would result in the subject being classified as Not
eligible to participate in this study.
19. Neurological, psychiatric or social conditions that affect compliance with
study requirements, significantly increase the risk of AEs, or affect the
subject's ability to provide written ICF.
17. History of other primary malignant tumors, except for the following:
- Cured malignancy, no known active disease for ≥2 years before study enrollment
and extremely low risk of recurrence;
- Nonmelanoma skin cancer or lentigo maligna that has been adequately treated and
without evidence of disease recurrence;
- Carcinoma in situ that has been adequately treated and without evidence of
disease recurrence.
18. Known history of immunodeficiency.
19. History of allogeneic organ transplantation and allogeneic hematopoietic stem cell
transplantation.
20. Long-term use of systemic hormones or immunosuppressive drugs that are not reduced
to physiological doses or discontinued 4 weeks before the first dose, excluding:
intranasal inhaled local steroid treatment or local steroid injection (such as
intra-articular injection) ; Systemic corticosteroid treatment not exceeding 10
mg/day of prednisone or its equivalent physiological dose; Glucocorticoids as
preventive medication for allergic reactions (such as medication before CT) and
vomiting prevention medication specified in the protocol. Requires long-term
systemic corticosteroids or any other immunosuppressive drug therapy, excluding
inhaled corticosteroids.
21. Suffering from active autoimmune diseases or inflammatory diseases [including
inflammatory bowel disease (such as ulcerative colitis, Crohn's disease, etc.),
celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome or Wegener
syndrome ( Granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis,
hypophysitis, uveitis, etc.], or a history of this disease within the past 2 years.
Subjects with vitiligo, psoriasis, alopecia or Grave's disease who do not require
systemic treatment within the past 2 years, hypothyroidism who only require thyroid
hormone replacement therapy, and type 1 diabetes who only require insulin
replacement therapy can be enrolled. . Subjects who are only positive for autoimmune
antibodies need to confirm whether there is an autoimmune disease according to the
researcher's judgment.
22. Previous treatment with antibody drug conjugates based on topoisomerase inhibitors.
23. For subjects receiving drug treatment, there is a history of allergy to
corresponding drugs or preparations.
24. For subjects receiving drug treatment, there are contraindications to the
corresponding drugs.
25. For subjects receiving drug treatment, there has been a history of adverse reactions
related to the corresponding drugs that led to permanent discontinuation of the
drug.
26. Pregnant or lactating female subjects.
27. Other researchers believe that you are not eligible to participate in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
March 15, 2024
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Harbin Medical University
Agency class:
Other
Collaborator:
Agency:
Innovent Biologics (Suzhou) Co. Ltd.
Agency class:
Industry
Source:
Harbin Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06321913
