Trial Title:
Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes
NCT ID:
NCT05608785
Condition:
Gastric Cancer
Gastroesophageal-junction Cancer
Conditions: Official terms:
Adenocarcinoma
Capecitabine
Oxaliplatin
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Unknown status
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IBI315
Description:
IBI315 is a recombinant fully humanized anti-programmed death receptor 1 (PD-1) and
humanized anti-human epidermal growth factor receptor 2 (HER2) bispecific antibody
injection.
Arm group label:
HER2 protein positive 3+ or FISH amplification or HER protein 2+ but FISH amplification
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
Oxaliplatin is a type of chemotherapy. It is used as a treatment for different types of
cancer, including gastric cancer.
Arm group label:
HER2 protein positive 3+ or FISH amplification or HER protein 2+ but FISH amplification
Arm group label:
Her2 protein, Claudin18.2 protein were negative
Arm group label:
Positive for Claudin 18.2 protein
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
Capecitabine is a type of chemotherapy. It is used as a treatment for different types of
cancer, including gastric cancer.
Arm group label:
HER2 protein positive 3+ or FISH amplification or HER protein 2+ but FISH amplification
Arm group label:
Her2 protein, Claudin18.2 protein were negative
Arm group label:
Positive for Claudin 18.2 protein
Intervention type:
Drug
Intervention name:
TST001
Description:
TST001 is a high-affinity humanized monoclonal antibody targeting Claudin 18.2 with
enhanced antibody-dependent cytotoxic (ADCC) and complement-dependent cytotoxic (CDC)
activity, showing potent antitumor activity in xenograft assays.
Arm group label:
Positive for Claudin 18.2 protein
Intervention type:
Drug
Intervention name:
TQB2450
Description:
TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1),
which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores
T cell activity, thus enhancing immune response and has potential to treat various types
of tumors.
Arm group label:
Her2 protein, Claudin18.2 protein were negative
Arm group label:
Positive for Claudin 18.2 protein
Intervention type:
Drug
Intervention name:
Anrotinib
Description:
Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and
proliferative signaling.
Arm group label:
Her2 protein, Claudin18.2 protein were negative
Summary:
Abstract Study title: Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study
of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the
Stomach or Gastroesophageal Junction Based on Different Genotypes Protocol No: GC-MATCH
Initiator: Henan Cancer Hospital Nature of study Investigator-initiated exploratory study
Subjects Advanced first-line gastric cancer or adenocarcinoma of the gastroesophageal
junction Objective: To evaluate the efficacy and safety of different first-line treatment
options for unresectable locally advanced/advanced gastric or combined gastroesophageal
adenocarcinoma with different gene/protein types.
Evaluation criteria: To evaluate the adverse effects of drugs using the NCI CTCAE V5.0
criteria.
RECIST1.1 criteria were used to evaluate drug efficacy Study endpoints: Primary
indicators Objective Response Rate (ORR) Secondary indicators 1. drug safety. 2. disease
control rate DCR (CR+PR+SD). 3. duration of remission DoR. 4. disease-free survival (PFS)
and overall survival time (OS). 5. R0/R1 surgical resection rate Study design:
Single-center umbrella clinical trial Planned number of enrollment: Total 39-45 cases
Sample size estimation: This is an exploratory study and sample size was not calculated
Statistical methods: Selection of data for statistical analysis Full Analysis Set (FAS):
The efficacy analysis was performed on all patients who were enrolled and used the drug
at least once, according to the principle of intentional analysis (ITT).
Per-protocol Set: Cases with at least one oncologic efficacy assessment, compliance with
the trial protocol, good compliance, no prohibited drugs during the trial, and completion
of the case report form.
Safety Analysis Set: All patients who had used the trial drug at least once and had a
safety record after the drug was administered were enrolled in the Safety Analysis Set.
Statistical analysis plan Validity analysis: for the efficacy index PFS, the Kaplan-Meier
method will be used to estimate its median time and column Statistical methods: Out of
two-sided 95% confidence intervals. Disease control rate (DCR = CR+PR+SD) and objective
remission rate (ORR = CR+PR) were calculated using Fisher exact probability and bilateral
95% confidence intervals were presented.
Safety analysis: descriptive statistical analysis was used to tabulate the AEs that
occurred in this trial. laboratory test results were described as normal before the trial
but abnormal after treatment and in relation to the trial drug when abnormal changes
occurred.
Treatment protocol:
All subjects in this study were first tested for genes/proteins (HER2 protein, HER2FISH,
PD-L1 protein 22C3, Claudin18.2, MMR) and received treatment in different groups
according to gene/protein expression.
Group 1 HER protein positive 3+ or FISH amplification or HER protein 2+ but FISH
amplification Initial treatment (4-6 cycles): IBI315 injection, oxaliplatin, capecitabine
Group 2 Claudin18.2 protein-positive Initial treatment (4-6 cycles): PD-L1 monoclonal
antibody, TST001 injection, oxaliplatin, capecitabine Group 3 Her protein and Claudin18.2
protein were negative Initial treatment (4-6 cycles): TQB2450 injection, Anrotinib,
Oxaliplatin, Capecitabine Patients can undergo radical gastric cancer surgery or radical
gastric cancer surgery + local treatment during the maintenance treatment phase if their
condition is stable and after in-hospital MDT consultation. The duration of maintenance
treatment was 2 years from the time of enrollment.
Principal Investigator: Luo Suxia, Li Ning Group leader unit: Henan Cancer Hospital
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Voluntarily sign the informed consent form for this study.
- Male or female patients aged 18-75 years.
- unresectable advanced or metastatic gastric cancer or adenocarcinoma of the
gastroesophageal junction (including indolent cell carcinoma, mucinous
adenocarcinoma, hepatoid adenocarcinoma) confirmed by pathological (histological or
cytological) examination.
- >6 months from the end of prior (neo)adjuvant chemotherapy/adjuvant radiotherapy to
the time of disease recurrence
- at least one measurable lesion or evaluable lesion according to RECIST version 1.1;
measurable lesions should not have received local treatment such as radiotherapy
(lesions located within the area of previous radiotherapy may also be optional
targets if progression is confirmed and they meet RECIST 1.1 criteria)
- ECOG score: 0 to 1.
- Life expectancy ≥ 3 months.
- Adequate organ function, with the following laboratory test values required at
screening.
- Routine blood test criteria to be met. Hemoglobin level (HB) ≥ 90 g/L (no blood
transfusion within 14 days). Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelet
count (PLT) ≥100×109/L (no interleukin 11 or TPO within 14 days). White blood cell
count (WBC) ≥4.0×109/L (no granulocyte stimulating factor within 14 days).
- Biochemical tests are required to meet the following criteria. Serum total bilirubin
(TBIL) ≤ 1.5 times the upper limit of normal (ULN). ALT and AST ≤ 2.5 ULN. Cr ≤ 1.5
ULN or creatinine clearance (CCr) ≥ 60 ml/min, (Cockcroft-Gault formula).
Serum albumin ≥ 25 g/L (2.5 g/dL). For subjects with liver metastases, AST and ALT must
be ≤ 5 x ULN, leukocytes ≥ 4 x 109/L, untransfused platelets ≥ 100 x 109/L, absolute
neutrophil value (ANC) without granulocyte-stimulating factor treatment ≥ 1.5 x 109/L,
hemoglobin ≥ 90 g/L
- Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ low limit
of normal (50%).
- Adequate coagulation, defined as an international normalized ratio (INR) or
prothrombin time (PT) ≤ 1.5 times ULN.
- Women of childbearing potential are required to use highly effective contraception
for the duration of the study, and for the period after the last dose and for at
least 180 days after chemotherapy. It is recommended that contraception be initiated
at least 3 months prior to study drug administration; non-sterile men are required
to use highly effective contraception for the duration of the study and for at least
180 days after both the last dose and chemotherapy. It is recommended that
contraception be initiated at least 3 months prior to study drug administration.
- If local treatment of metastases, such as radiotherapy or ablation, is performed,
they may also be enrolled after 14 days of washout as long as an assessable lesion
is still present and the local treatment is not followed by anti-tumor therapy such
as targeted, chemotherapy or immunotherapy.
Exclusion Criteria:
- Hypersensitivity to any of the test drugs and their excipients, or a history of
severe allergy, or a contraindication to the test drug.
- A history or active stage of autoimmune disease.
- symptomatic/asymptomatic brain metastases
- CT suggestive of definite ulcerative lesions or positive fecal occult blood (risk of
bleeding and suitability for enrollment as determined by the investigator)
- History of abnormal bleeding (except epistaxis) complained of 14 days prior to
enrollment
- previous allogeneic bone marrow transplantation or organ transplantation
- congenital pulmonary fibrosis, drug-induced pneumonia, mechanized pneumonia, or
CT-confirmed active pneumonia
- HIV positive test, active hepatitis B or C, active tuberculosis.
- Uncontrolled cancer pain.
- previous live attenuated vaccine within 4 weeks prior to study entry or expected to
be administered during or within 5 months of the end of the trial
- Prior treatment with PD-1/PD-L1 antibodies, CTLA-4 antibodies, or other therapies
targeting PD-1/PD-L1 and/or VEGFR inhibitors or have not recovered from adverse
events caused by dosing >4 weeks prior (i.e., have not returned to ≤ grade 1 or
baseline levels)).
- Systemic application of glucocorticoids or immunosuppressants within 2 weeks prior
to trial start (note: inhaled glucocorticoids and salicorticoids are permitted).
- Known presence of symptomatic CNS metastases and/or carcinomatous meningitis.
Patients with a history of CNS metastases or spinal cord compression may be enrolled
in the study if they are clearly treated and clinically stable after discontinuation
of anticonvulsants and steroids for 4 weeks prior to the first dose of the study.
- Have a contraindication to hormone use.
- Have multiple factors that interfere with oral drug administration (e.g., inability
to swallow, chronic diarrhea, and intestinal obstruction)
- peripheral neuropathy ≥ NCI CTCAE grade 2.
- Uncontrollable or symptomatic hypercalcemia.
- infections requiring antibiotics within 14 days prior to the start of the trial
- chronic enterocolitis.
- Patients with bone metastases at risk of paraplegia.
- Patients with any severe and/ or uncontrolled disease, including: Patients with
suboptimal blood pressure control (systolic blood pressure ≥ 150 mmHg or diastolic
blood pressure ≥ 100 mmHg) on antihypertensive medications; patients with class II
or higher myocardial ischemia or myocardial infarction, arrhythmias (including QT
interval ≥ 480 ms); class III-IV cardiac insufficiency by NYHA criteria, or cardiac
ultrasound suggestive of left ventricular ejection fraction ( LVEF) <50% in
patients. Active or uncontrolled severe infections. Liver disease such as cirrhosis,
decompensated liver disease, chronic active hepatitis. Poorly controlled diabetes
mellitus (fasting blood glucose (FBG) >10 mmol/L). Urine routine suggestive of urine
protein ≥++ and confirmed 24-hour urine protein quantification >1.0 g.
- Long-term untreated wounds or fractures 23) Subjects who are unable to receive a
trans-peripheral central venous placement (PICC)
- Subjects with abnormal coagulation (INR > 1.5 or APTT > 1.5 × ULN), with bleeding
tendency or on thrombolytic or anticoagulant therapy. Known hereditary or acquired
bleeding and thrombotic tendencies such as: hemophilia, impaired coagulation skills,
thrombocytopenia, hypersplenism, etc. Active bleeding within 14 prior to study
entry.
- Major surgical procedure (craniotomy, open-heart or open-heart surgery) within 4
weeks prior to the first dose of study, or anticipated need for major surgery during
study treatment, or non-diagnostic surgery within 4 weeks prior to the start of the
trial.
- history of gastrointestinal perforation and/or fistula within 3 months prior to
enrollment in treatment; or arterial/venous thrombotic events such as
cerebrovascular accidents (except stable cerebral infarction as assessed by the
investigator), deep vein thrombosis, and pulmonary embolism (except if cured)
- Clinically significant thoracoabdominal fluid, including any thoracoabdominal fluid
that is detectable on physical examination, previously treated or currently still
requiring treatment Those with only a small amount of thoracic ascites on imaging
but asymptomatic, which the investigator assesses does not require treatment may be
enrolled.
- Interstitial lung disease requiring steroid hormone therapy.
- uncontrolled metabolic disorders or other non-malignant organ or systemic diseases
or secondary reactions to cancer that can lead to higher medical risk and/or
uncertainty in survival evaluation
- Patients with significant malnutrition.
- Patients with a history of psychotropic substance abuse and inability to abstain or
with psychiatric disorders
- those with a history of immunodeficiency, including testing positive for HIV or
having other acquired, congenital immunodeficiency disorders, or a history of organ
transplantation
- History of other primary malignancies, except for 1) malignancies in complete
remission for at least 2 years prior to enrollment and requiring no other treatment
during the study period; 2) non-melanoma skin cancers or malignant freckled nevi
that have been adequately treated and have no evidence of disease recurrence; and 3)
carcinomas in situ that have been adequately treated and have no evidence of disease
recurrence.
- Female patients who are pregnant or breastfeeding.
- those who, in the judgment of the investigator, have a serious concomitant disease
that jeopardizes patient safety or interferes with the patient's ability to complete
the study
- Participating in another trial within 30 days prior to the start of the trial, or
planning to participate in another trial while the trial is ongoing.
- Inclusion in the row with the most stringent conditions, if there is duplication.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
January 1, 2023
Completion date:
October 1, 2024
Lead sponsor:
Agency:
Henan Cancer Hospital
Agency class:
Other
Source:
Henan Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05608785
