| Eligibility |
Inclusion criteria:
1. Stage IIa only: advanced or metastatic solid tumor confirmed by histopathology or
cytology.
2. Only stage IIb and III: Patients with mCRC confirmed by histopathology or cytology,
who are not suitable for radical surgical excision or local therapy, and who have not
previously received systemic antitumor therapy for CRC (including systemic
chemotherapy, molecular targeted drug therapy, biotherapy and investigational therapy,
and have completed adjuvant chemotherapy for =6 months) can be admitted to the group.
3. Age range from 18 to 75 years old (including the critical value), gender is not
limited.
4. Proof of HER2-positive (IHC) 3+, or IHC 2+ and FISH +, by immunohistochemical (IHC)
staining and/or fluorescence in situ hybridization (FISH), and wild type KRAS, NRAS,
and BRAF genes. HER2 positive status was interpreted according to the current Chinese
guidelines for detecting HER2 in gastric cancer.
5. According to the researchers' judgment, CAPEOX scheme is suitable.
6. At least one measurable lesion according to RECIST 1.1 criteria (tumor lesion located
in the area of prior radiotherapy or other local regional treatment site is generally
not considered as a measurable lesion unless it shows definite progression or persists
three months after radiotherapy).
7. The physical status score of the Eastern Oncology Consortium (ECOG) was 0-1.
8. Expected survival =3 months.
9. Adequate organ function: 1) Blood system (no blood transfusion or hematopoietic
stimulating factor treatment 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 for Gilbert
syndrome; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3.0
times ULN, liver metastasis or liver cancer patients need AST and ALT=5.0 times ULN.
3. Renal function: serum creatinine (Cr) =1.5 ULN; If creatinine Creatinine clearance
(Ccr) =50 ml/min (calculated by Cockcroft-Gault formula) was required at 1.5 ULN.
Coagulation function: prothrombin International Normalized ratio (INR) =1.5 ULN,
activated partial thrombin time (APTT) =1.5 ULN.
10. Eligible patients (male and female) who are fertile must agree to use a reliable
contraceptive method (hormonal or barrier method or abstinence) with their partner
during the trial period and for at least 6 months after the last medication; Women of
reproductive age must have a negative blood or urine pregnancy test 7 days before
first use of the study drug.
11. Subjects must give informed consent to the study prior to the study and voluntarily
sign written informed consent.
Exclusion criteria:
1. Stage IIa only: chemotherapy, radiotherapy, biotherapy, endocrine therapy,
immunotherapy and other antitumor therapies were received within 4 weeks prior to the
first use of the study drug, except for the following: 1 nitrosourea or mitomycin C
was used within 6 weeks prior to the first use of the study drug; 2 Oral
administration of fluoripyritics and small molecule targeted drugs 2 weeks prior to
the first use of the study drug or within 5 half-lives of the drug, whichever is
longer; 3 Chinese patent drugs with anti-tumor indications were used within 2 weeks
prior to the first use of the investigational drug.
2. Have received other investigational drugs or treatments that are not on the market
within 4 weeks prior to use of the investigational drug.
3. Stage IIa only: Adverse reactions to previous antitumor therapy have not yet returned
to the NCI CTCAE 5.0 scale evaluation = Level 1 or relevant provisions of inclusion
criteria (except for toxicities without safety risks as determined by the
investigators, such as alopecia, grade 2 peripheral neurotoxicity, stable
hypothyroidism after hormone replacement therapy, etc.).
4. Known hypersensitivity to any antibody-class drug (NCI CTCAE 5.0 rating =3) or to
investigational drug, CAPEOX protocol active ingredient or inactive excipients.
5. Confirmed mismatch repair defect (dMMR) or high microsatellite instability (MSI-H)
solid tumors (unless subject is unable to receive immune checkpoint inhibitors due to
a pre-existing medical condition, or unknown MSI/MMR status).
6. Had major organ surgery (excluding needle biopsy) or significant trauma, or required
elective surgery, within 4 weeks prior to initial use of the study drug.
7. Received systemic administration of corticosteroids (prednisone > 10 mg/day or
equivalent dose of the same drug) or other immunosuppressant therapy, except:
treatment with topical, ocular, intraarticular, intranasal, and inhaled
corticosteroids; Short-term use of glucocorticoids for prophylactic treatment (e.g. to
prevent shadow allergy).
8. Use of immunomodulatory drugs within 14 days (Appendix 5).
9. Received any live vaccine within 4 weeks prior to the first administration of the
study drug.
10. Have previously received allogeneic hematopoietic stem cell transplantation or organ
transplantation.
11. There are clinical symptoms of brain parenchymal metastasis or meningeal metastasis.
Patients with BMS who had been treated were enrolled if magnetic resonance imaging
(MRI) or computed tomography (CT) showed no signs of progression at least 8 weeks
after the end of treatment and 4 weeks before the first use of the study drug.
12. There is an active infection that currently requires intravenous anti-infective
therapy.
13. A history of immunodeficiency, including a positive test for human immunodeficiency
virus (HIV) antibodies.
14. Active hepatitis B (HBsAg positive and HBV-DNA=1.0×103 copies /mL or =2000IU/mL,
active hepatitis C (HCV-RNA> 1.0×103 copies /mL or > 100 IU/mL).
15. Severe and uncontrollable lung disease (severe infectious pneumonia, interstitial lung
disease, etc.).
16. Have a history of serious cardiovascular and cerebrovascular diseases, including but
not limited to: 1. Have serious cardiac rhythm or conduction abnormalities, such as
ventricular arrhythmias requiring clinical intervention, degree II-III
atrioventricular block, etc.; 2 QT interval (QTcF) mean corrected by Fridericia method
> 470 ms;3 Acute coronary syndrome, congestive heart failure, aortic dissection,
stroke, or other grade 3 or above cardiovascular and cerebrovascular events occurred
within 6 months prior to initial administration;4 Present with heart failure or left
ventricular ejection fraction (LVEF)< of the New York Heart Association (NYHA)
cardiac function grade =II; 50%;5. Clinically uncontrollable hypertension.
17. Have an active or past autoimmune disease with a risk of recurrence (e.g., systemic
lupus erythematosus, class Rheumatoid arthritis, vasculitis), clinically stable
autoimmune thyroid disease, type I diabetes, vitiligo, Children with cured atopic
dermatitis and psoriasis that does not require systemic treatment (within the last 2
years) are excluded.
18. Non-melanoma skin cancer that has been clinically cured for more than 2 years and is
currently suffering from other malignant tumors, limitations Exceptions include
prostate cancer, carcinoma in situ (such as cervical carcinoma in situ), etc.
19. There was clinically uncontrollable third space effusion, which was not suitable for
inclusion by the investigator.
20. Known alcohol or drug dependence.
21. Have mental disorders or poor compliance.
22. Pregnant or lactating women.
23. The investigator believes that the subjects have a history of other serious systemic
diseases or are not suitable to participate in this clinical study for other reasons.
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