Trial Title:
Anlotinib, TQB2450 (PD-L1 Inhibitor), and Albumin-bound Paclitaxel Regimens in the Treatment of GC/GEJA
NCT ID:
NCT06222944
Condition:
Gastric Cancer
Adenocarcinoma of Esophagogastric Junction
Conditions: Official terms:
Adenocarcinoma
Stomach Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
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:
Anlotinib
Description:
Anlotinib: 12mg PO, QD, D1-14, Q3W;
Arm group label:
Anlotinib, TQB2450 and Albumin-bound Paclitaxel
Other name:
Anlotinib Hydrochloride Capsule
Intervention type:
Drug
Intervention name:
TQB2450
Description:
TQB2450: 1200 mg, IV, D1, Q3W
Arm group label:
Anlotinib, TQB2450 and Albumin-bound Paclitaxel
Intervention type:
Drug
Intervention name:
Albumin-Bound Paclitaxel
Description:
125mg/m2 IV D1,8，Q3W
Arm group label:
Anlotinib, TQB2450 and Albumin-bound Paclitaxel
Other name:
Paclitaxel (albumin-bound)
Other name:
Paclitaxel for injection(Albumin Bound)
Summary:
This study aims to assess the efficacy and safety of a combination therapy consisting of
Anlotinib, TQB2450 (a PD-L1 inhibitor), and Albumin-bound Paclitaxel regimens in patients
with advanced gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA) who
have failed the previous treatment with Claudin18.2 (CLDN18.2)-related regimens.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Voluntarily join this study, sign the informed consent form, and have good
compliance;
- Pathologically (histologically or cytologically) confirmed HER2/neu-negative (or
HER2/neu status unclear) advanced gastric cancer or gastroesophageal junction
adenocarcinoma;
- Patients who have failed first-line treatment with CLDN18.2-related regimen
(CLDN18.2 drugs include CLDN18.2 monotherapy, CLDN18.2 dual therapy, CLDN18.2 ADC or
CLDN18.2 CART therapy, treatment regimen includes CLDN18.2 combined with
chemotherapy or immunotherapy or other systemic therapy) and the time from the end
of the last treatment with CLDN18.2-related drugs is more than two weeks;
- According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1,
at least one measurable lesion, which can be accurately measured in at least one
direction (the maximum diameter needs to be recorded) by magnetic resonance imaging
(MRI) or computed tomography (CT), with the longest diameter at baseline ≥10 mm (if
it is a lymph node, the short diameter is required to be ≥15 mm); the measurable
lesions should not have received local treatment such as radiotherapy (lesions in
the previous radiotherapy area, if confirmed to have progressed and meet the RECIST
1.1 criteria, can also be selected as target lesions);
- Male or female patients aged ≥18 years and ≤75 years;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score: 0-1;
- Expected survival ≥3 months;
- Adequate organ function, requiring the following laboratory test values at
screening:
- Hemoglobin (HB) ≥80g/L (no blood transfusion within 14 days);
- Absolute neutrophil count (ANC) ≥1.5×109/L;
- Platelet count (PLT) ≥75×109/L (no use of interleukin 11 or TPO within 14
days);
- White blood cell count (WBC) ≥3.0×109/L (no use of granulocyte stimulating
factor within 14 days).
- Serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN);
- ALT and AST ≤2.5 ULN, if there is liver metastasis, then ALT and AST ≤5×ULN;
- Creatinine (Cr) ≤1.5 ULN or creatinine clearance rate (CCr) ≥60ml/min,
(Cockcroft-Gault formula);
- Adequate coagulation function, defined as international normalized ratio (INR)
or prothrombin time (PT) ≤1.5 times ULN;
- Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥
lower limit of normal (50%);
- Cardiac enzyme spectrum: within normal range;
- Women of childbearing age must take appropriate contraceptive measures from
screening to 3 months after stopping the study treatment and must be non-lactating
patients. Serum or urine pregnancy test negative within 7 days before enrollment in
the study, or meet one of the following criteria to prove that there is no risk of
pregnancy:
- a) Postmenopausal is defined as age over 50 years and amenorrhea for at least
12 months after stopping all exogenous hormone replacement therapy;
- b) Women under 50 years of age, if amenorrhea for 12 months or more after
stopping all exogenous hormone therapy, and luteinizing hormone (LH) and
follicle-stimulating hormone (FSH) levels are within the laboratory
postmenopausal reference range, can also be considered as postmenopausal;
- c) Have undergone irreversible sterilization surgery, including hysterectomy,
bilateral oophorectomy, or bilateral salpingectomy, but excluding bilateral
tubal ligation; For men, they must agree to use appropriate methods of
contraception or have undergone surgical sterilization during the trial and 8
weeks after the last administration of the trial drug;
Exclusion Criteria:
- For cohort 1, patients who have previously received anlotinib hydrochloride
treatment or other anti-angiogenic small molecule tyrosine kinase inhibitors (TKIs)
within 6 months. Patients who have stopped treatment with other anti-angiogenic
small molecule TKIs for more than 6 months are allowed to enroll; For cohort 2 and
cohort 3, patients who have received PD-L1 immune checkpoint inhibitor treatment in
the first line are excluded, but patients who have received PD-1 or CTLA-4 immune
checkpoint inhibitor treatment in the first line are allowed, if they have any of
the following immune-related medical history and treatment history, they are
excluded:
- Have any active autoimmune disease or history of autoimmune disease (such as
but not limited to autoimmune hepatitis, interstitial pneumonia, enteritis,
vasculitis, nephritis; requiring bronchodilators for medical intervention of
asthma); but the following patients are allowed to enroll: vitiligo, psoriasis,
alopecia that do not require systemic treatment, type I diabetes that is well
controlled, hypothyroidism that has normal thyroid function after replacement
therapy;
- Diagnosed with immunodeficiency or receiving systemic corticosteroid therapy or
any other form of immunosuppressive therapy (dose >10mg/day of prednisone or
other equivalent hormones), and continuing to use it within 2 weeks before the
first administration;
- Received any live vaccine, attenuated vaccine (including anti-infective
vaccines, such as influenza vaccine, varicella vaccine, etc.), or inactivated
vaccine within 4 weeks before enrollment and plan to receive live
vaccine/attenuated vaccine/inactivated vaccine during the study; used systemic
immunostimulants (including but not limited to interferon and IL-2) within 2
weeks before the start of the study treatment;
For Cohort 3, patients who have previously received anlotinib hydrochloride or other
anti-angiogenic small molecule tyrosine kinase inhibitors (TKIs) within 6 months.
Patients who have stopped treatment with other anti-angiogenic small molecule TKIs for
more than 6 months are allowed to enroll;
- Patients who have received anti-tumor treatment with traditional Chinese medicine
within the past two weeks (the traditional Chinese medicine contains the following
medicinal materials such as Brucea javanica, Coix seed, Lentinan, Cantharidin, Toad
skin, Astragalus, Sophora, Ugonin, Chebula, Icariin, etc.), but patients who have
stopped taking anti-tumor treatment with traditional Chinese medicine for more than
two weeks are allowed to enroll;
- Patients who have received ≥1 other systemic systemic anti-tumor treatment
(including but not limited to chemotherapy, immunotherapy, targeted therapy, and
other systemic treatment regimens) after failing CLDN18.2-related regimen treatment,
but palliative local treatment (including radiotherapy and other local treatment
regimens) for local lesions (non-target lesions) >two weeks later are allowed to
enroll;
- Patients who have previously received allogeneic bone marrow transplantation or
organ transplantation;
- Congenital pulmonary fibrosis, drug-induced pneumonia, organizing pneumonia, or
CT-confirmed active pneumonia;
- Patients with symptomatic central nervous system metastases and/or carcinomatous
meningitis. Patients with a history of central nervous system metastases or spinal
cord compression, if they have received treatment and stopped using anticonvulsants
and steroids 4 weeks before the first administration of the study and have
clinically stable performance, can enroll in the study;
- ≥ NCI CTCAE grade 2 peripheral neuropathy;
- Infection requiring antibiotics within 14 days before the start of the trial;
- Patients with bone metastases at risk of paraplegia;
- Patients with any severe and/uncontrolled disease, including:
- Patients with poor blood pressure control using antihypertensive drugs
(systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg);
patients with grade II or higher myocardial ischemia or myocardial infarction,
arrhythmia (including QT interval ≥480ms); patients with III-IV heart failure
according to NYHA criteria or cardiac ultrasound examination suggesting left
ventricular ejection fraction (LVEF) <50%;
- Poorly controlled diabetes (fasting blood glucose (FBG) >10mmol/L);
- Urinalysis suggests urine protein ≥++, and 24-hour urine protein quantification
>1.0 g is confirmed;
- Received major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks
before the study, or expected to need major surgery during the study treatment, or
non-diagnostic surgery within 4 weeks before the start of the trial;
- History of gastrointestinal perforation and/or fistula within 6 months before
enrollment; or history of arterial/venous thromboembolic events, such as
cerebrovascular accident (stable cerebral infarction excluded by researcher
evaluation), deep vein thrombosis, and pulmonary embolism;
- Clinically significant pleural effusion, including any pleural effusion that can be
found by physical examination, pleural effusion that has been treated in the past or
still needs treatment. Patients with only a small amount of pleural effusion shown
by imaging but no symptoms, and who do not need treatment according to the
researcher's evaluation, can be enrolled;
- Body mass index (BMI) <17.0 kg/m² or weight loss of ≥10% within 2 months before
screening;
- Patients with a history of psychotropic drug abuse and unable to quit or have mental
disorders;
- Patients with active hepatitis B or hepatitis C, HIV-positive patients, patients
with active tuberculosis;
- CT suggests definite ulcerative lesions, or occult blood in stool ++ or above;
- History of abnormal bleeding (except epistaxis) within 1 month before enrollment;
- History of other primary malignant tumors, except for the following: 1) Malignant
tumors that have been completely remitted for at least 2 years before enrollment and
do not require other treatment during the study; 2) Non-melanoma skin cancer or
malignant melanocytic nevus that have been adequately treated and have no evidence
of disease recurrence; 3) In situ carcinoma that has been adequately treated and has
no evidence of disease recurrence;
- Pregnant or lactating female patients;
- According to the researcher's judgment, patients with severe accompanying diseases
that endanger the patient's safety or affect the patient's completion of the study;
- Participated in other trials within 30 days before the start of the trial, or plan
to participate in other trials during the trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Cancer Hospital
Address:
City:
Beijing
Zip:
100142
Country:
China
Contact:
Last name:
Yakun Wang, PhD
Phone:
0086-010-88196340
Email:
wykun1991@126.com
Start date:
February 25, 2024
Completion date:
August 25, 2026
Lead sponsor:
Agency:
Peking University
Agency class:
Other
Collaborator:
Agency:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Agency class:
Industry
Source:
Peking University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06222944
