Trial Title:
To Evaluate IAH0968 in Combination With CAPEOX in HER2-positive Gastric Cancer
NCT ID:
NCT06504732
Condition:
Stomach Neoplasms
Solid Tumor
Conditions: Official terms:
Stomach Neoplasms
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IAH0968
Description:
Subjects were treated with IAH0968 in combination with or without the CAPEOX regimen in
the corresponding groups. Every 3 weeks was defined as a treatment cycle and IAH0968 was
used for a maximum of 35 cycles.
Arm group label:
Cohort 1
Arm group label:
Cohort 2
Arm group label:
Cohort 3
Summary:
The safety, tolerability, and determination of the maximum tolerated dose (MTD) of the
combination therapy were first evaluated for IAH0968 in combination with or without the
CAPEOX regimen in unsystematically treated subjects with HER2-expressing
advanced/metastatic colorectal or gastric cancers (including adenocarcinomas of the
gastro-esophageal junction) or HER2-hypo-expressing advanced/metastatic solid tumors. The
efficacy of IAH0968 in combination with the CAPEOX regimen versus trastuzumab in
combination with the CAPEOX regimen in subjects with HER2-positive advanced/metastatic
gastric cancer, including gastro-esophageal junction adenocarcinoma, was then assessed by
progression-free survival (PFS) according to the Research and Evaluation Criteria for the
Evaluation of Efficacy in Solid Tumors (RECIST) 1.1.
Detailed description:
This clinical study is a randomized, multicenter Phase II/III clinical study to
investigate the efficacy of IAH0968 in combination or not in combination with the CAPEOX
regimen in the treatment of subjects with HER2-expressing advanced/metastatic solid
tumors and gastric cancer. The study is divided into two study phases: a Phase II
clinical study and a Phase III clinical study.
Adverse events and adverse reactions were assessed in the study through clinical
observation, vital signs monitoring, laboratory tests, etc., while PK, ADA and other
relevant samples were collected; and using RECIST 1.1 as the standard for tumor
assessment, subjects were assessed for tumors every 6 weeks starting from the first
infusion of the study drug until the occurrence of disease progression, the initiation of
new antitumor therapy, and the judgement of the investigator that it was not suitable for
continued participation (e.g., development of intolerable adverse reactions), loss to
visit, voluntary withdrawal, death, or study termination/suspension.
Upon withdrawal or termination of treatment (+7 days), subjects should be visited for
termination of treatment (except in the case of death and loss to follow-up), as far as
possible, prior to the initiation of new antitumor therapy, with relevant laboratory
investigations and ADA samples, and thereafter followed up by telephone every 12 weeks
(±7 days) for survival (OS) until loss to follow-up or death.
The phase II study was an open-label, nonrandomized clinical study, which was planned to
be divided into 3 cohorts.The phase III study used a randomized, parallel-controlled,
multicenter study design.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1) Age 18~75 years old (including critical mass), gender is not limited. 2) Phase
II cohort 1 and III only: patients with locally advanced or metastatic gastric
cancer (including adenocarcinoma of the gastro-esophageal junction) diagnosed
by histopathology, unsuitable for radical surgical resection or localized
treatment, and who have not received systemic antitumor therapy (including
systemic chemotherapy, molecularly-targeted drug therapy, biologic therapy, and
other investigational therapeutic agents) for GC (except for adjuvant
chemotherapy for >6 months), and who have demonstrated disease progression; and
patients who have been diagnosed by immunohistochemistry (IHC) staining and/or
fluorescence in situ hybridization (FISH). and demonstrated disease progression
excepted); HER2 positivity (IHC 3+, or IHC 2+ and FISH +) demonstrated by
immunohistochemical (IHC) staining and/or fluorescence in situ hybridization
(FISH).
3) Phase II Cohort 2 only: Have histologically or cytologically confirmed advanced
malignant solid tumors that have failed standard treatment, or for which no
standard treatment options are available, or for which standard treatment is
not applicable at this stage; and are HER2 underexpressed (IHC 2+ and FISH-, or
IHC 1+) as evidenced by immunohistochemistry (IHC) staining and/or fluorescence
in situ hybridization (FISH).
4) Phase II Cohort 3 only: with locally advanced or metastatic gastric cancer
(including gastro-oesophageal junction adenocarcinoma) or colorectal cancer
diagnosed by histopathology, unsuitable for radical surgical resection or
localized treatment, with no prior systemic (including systemic chemotherapy,
molecularly-targeted drug therapy, biologic therapy, and other investigational
therapeutic agents) antitumor therapy (having received adjuvant chemotherapy
for >6 months with evidence of disease progression), patients with wild-type
KRAS, NRAS, and BRAF genes (mCRC only); and HER2 low expression (IHC 2+ and
FISH-, or IHC 1+) demonstrated by immunohistochemical (IHC) staining and/or
fluorescence in situ hybridization (FISH).
5) At least 1 measurable lesion according to RECIST 1.1 criteria (tumor lesions
located in the area of prior radiotherapy or other localized regional treatment
sites are generally not considered measurable lesions unless the lesion shows
definite progression or persists after three months of radiotherapy).
6) Eastern Cooperative Oncology Group (ECOG) physical status score of 0 to 1. 7)
Have an expected survival of ≥ 3 months. 8) Adequate organ function:
- Hematologic system (no transfusion or hematopoietic stimulating factor therapy
within 14 days): absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count
(PLT) ≥ 90 × 109/L, hemoglobin (HGB) ≥ 90 g/L; Liver function: total bilirubin
(TBIL) ≤ 1.5 times the upper limit of normal (ULN), except Gilbert's syndrome;
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 times
the ULN, liver metastasis or hepatocellular carcinoma patients need to AST and
ALT ≤ 5.0 times the ULN and total bilirubin ≤ 3.0 times the ULN; Renal
function: serum creatinine (Cr) ≤1.5 times ULN; if creatinine >1.5 times ULN,
creatinine clearance (Ccr) ≥50 mL/min (calculated according to Cockcroft-Gault
formula);
④ Coagulation function: International Normalized Ratio (INR) ≤ 1.5 times ULN
for prothrombinogen, Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times
ULN, or INR and APTT ≤ 2.5 times ULN for patients with liver metastasis or
hepatocellular carcinoma.
9) Eligible patients (male and female) of childbearing potential must agree
to use a reliable method of contraception (hormonal or barrier method or
abstinence) with their partner for the duration of the trial and for at
least 6 months after the last dose; female patients of childbearing
potential must have a negative serum pregnancy test within 7 days prior to
the first dose of study drug.
10) Subjects must give informed consent for this study prior to the trial and
voluntarily sign a written informed consent form.
Exclusion Criteria:
-
1) Phase II Cohort 2 only: received antitumor therapy such as chemotherapy,
radiotherapy, biologic therapy, endocrine therapy, immunotherapy, etc. within 4
weeks prior to the first use of study drug, except for the following:
- Nitrosourea or mitomycin C within 6 weeks prior to first use of study drug;
② Oral fluorouracil analogs and small molecule targeted drugs for 2 weeks prior
to the first use of the study drug or within 5 half-lives of the drug
(whichever is longer);
③ Within 2 weeks prior to first use of the study drug for proprietary Chinese
medicines with antitumor indications.
2) Received other unlisted clinical investigational drug or therapy within 4
weeks prior to first use of the study drug.
3) Adverse effects of prior antineoplastic therapy have not returned to NCI
CTCAE 5.0 grade rating of ≤ grade 1 or relevant provisions of the
enrollment criteria (except for toxicities judged by the investigator to
pose no safety risk, such as alopecia, grade 2 peripheral neurotoxicity,
and hypothyroidism stabilized by hormone replacement therapy).
4) Known hypersensitivity to any antibody-based drug (NCI CTCAE 5.0 grade
rating ≥ 3) or hypersensitivity to the study drug and the active
ingredient or inactive excipients of the CAPEOX regimen.
5) Diagnosed defective mismatch repair (dMMR) or high microsatellite
instability (MSI-H) solid tumor (except unknown MSI/MMR status).
6) Major surgical procedure (excluding puncture biopsy), major trauma within
4 weeks prior to first use of study drug, or need for elective surgery
during the trial.
7) Received systemic glucocorticosteroids (prednisone > 10 mg/day or
equivalent) within 14 days prior to the first dose of study drug, except
for the following: treatment with topical, ocular, intra-articular,
intranasal, and inhaled glucocorticosteroids; and short-term prophylactic
glucocorticosteroids (e.g., for prevention of allergy to contrast media).
8) Other immunosuppressive therapy within 28 days or 5 half-lives (whichever
is longer) prior to first use of study drug.
9) Use of immunomodulatory drugs within 14 days prior to first use of study
drug.
10) Use of any live vaccine within 4 weeks prior to the first dose of study
drug.
11) Previous allogeneic hematopoietic stem cell transplantation or organ
transplantation.
12) Parenchymal brain metastases or meningeal metastases with clinical
symptoms.
13) Have an active infection that currently requires intravenous
anti-infective therapy.
14) Have a history of immunodeficiency, including a positive antibody test for
human immunodeficiency virus (HIV).
15) Have active hepatitis B (HBsAg positive and HBV-DNA positive or greater
than the upper limit of normal) and active hepatitis C (hepatitis C virus
antibody positive and HCV RNA positive or greater than the upper limit of
normal).
16) Have severe and uncontrollable lung disease (severe infectious pneumonia,
interstitial lung disease, etc.).
17) Have a history of severe cardiovascular disease, including but not limited
to:
- Having severe cardiac rhythm or conduction abnormalities, such as ventricular
arrhythmias requiring clinical intervention, degree II-III atrioventricular
block;
- Mean QT interval (QTcF) corrected by the Fridericia method > 470 ms;
③ Acute coronary syndrome, congestive heart failure, aortic coarctation,
stroke, or other grade 3 or higher cardiovascular event within 6 months
prior to the first dose;
④ Presence of New York Heart Association (NYHA) Cardiac Function Class ≥
Grade II heart failure or left ventricular ejection fraction (LVEF) < 50%,
or other structural heart disease judged by the investigator to be of high
risk;
⑤ Clinically uncontrolled hypertension. 18) Active, or previous autoimmune
disease with potential for relapse (e.g., systemic lupus erythematosus,
rheumatoid arthritis, vasculitis, etc.), except for clinically stable
autoimmune thyroid disease, type I diabetes mellitus, vitiligo, cured
atopic dermatitis in children, and psoriasis that does not require
systemic therapy (within the past 2 years).
19) Presence of other malignancies within 5 years prior to the start of
study dosing, except: malignancies for which cure can be expected
with treatment (including, but not limited to, adequately treated
thyroid cancer, cervical carcinoma in situ, basal or squamous cell
skin cancer, or ductal carcinoma in situ of the breast treated by
radical surgery).
20) Presence of clinically uncontrollable third interstitial fluid that,
in the judgment of the Investigator, makes enrollment inappropriate.
21) Known alcohol or drug dependence. 22) Have a mental disorder or poor
compliance. 23) Pregnant or lactating females. 24) In the opinion of
the investigator, the subject has a history of other serious systemic
disease or is otherwise unsuitable for enrollment in this clinical
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Hospital of China Medical University
Address:
City:
Shenyang
Country:
China
Start date:
July 2024
Completion date:
July 2028
Lead sponsor:
Agency:
SUNHO（China）BioPharmaceutical CO., Ltd.
Agency class:
Industry
Source:
SUNHO（China）BioPharmaceutical CO., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06504732
