| Eligibility |
Inclusion Criteria:
1. Male or female, age =18;
2. Expected survival time =3 months;
3. Patients with unresectable or metastatic colorectal cancer or gastric cancer confirmed
by histology or pathology:
Cohort_A: Patients with unresectable or metastatic gastric cancer, HER2-negative,
without standard treatment.
Cohort_B: Patients with MSS KRASwt BRAFwt unresectable or metastatic colorectal
cancer, failure of conventional chemotherapy combined with EGFR mab, and withdrawal of
EGFR mab for less than 3 months.
Cohort_C: MSS KRASwt BRAFwt patients with unresectable or metastatic colorectal cancer
who have failed multiline conventional chemotherapy (without EGFR monoclonal antibody
therapy).
Cohort_D: MSI-H KRASwt BRAFwt patients with unresectable or metastatic colorectal
cancer and previous first - or second-line treatment failure with anti-PD-1 (L1) mab
(excluding EGFR mab).
Cohort_E: MSI-H KRASwt BRAFwt patients with unresectable or metastatic colorectal
cancer who have previously failed first-line anti-PD-1 (L1) mab therapy.
Cohort_F: MSS KRASwt BRAFwt patients with unresectable or metastatic colorectal cancer
who have failed standard therapy with first-line oxaliplatin or irinotecan plus
fluorouracil plus or minus bevacizumab.
4. No previous anti-EGFR antibody therapy (excluding Cohort_B);
5. Agree to provide 4 specimens (thickness 5µm) of tumor tissue specimens (non-stained
sections (anti-removal)) archiving from primary or metastatic tumors;agree to provide
6 unstained sections surgical specimens (anti-removal, thickness 10µm) or fresh tissue
samples;
6. There must be at least one measurable lesion conforming to the RECIST V1.1 definition;
7. Cohort_A, B, C fitness scores =2, Cohort_D, E, F fitness scores =1;
8. Toxicity of previous antitumor therapy has been restored to =1 as defined by NCI-CTCAE
V5.0 (except for toxicity that the researchers judge to be of no safety risk, such as
hair loss, grade 2 peripheral neurotoxicity, and stabilized hypothyroidism after
hormone replacement therapy);
9. Organ function levels must meet the following requirements and meet the following
standards:
A) Bone marrow function: absolute value of neutrophil count (ANC) =1.5×109/L, platelet
count =100×109/L (platelet count =75×109/L in Patients with Cohort_A, B and C),
hemoglobin =90 g/L (hemoglobin =85 g/L in patients with Cohort_A, B and C); B) Liver
function: Total bilirubin TBIL=1.5×ULN (total bilirubin TBIL= 3×ULN in Gilbert's
syndrome, liver cancer or liver metastases); AST and ALT =2.5×ULN in patients without
liver metastasis; AST and ALT =5.0×ULN in patients with liver metastasis; C) Renal
function: Creatinine (Cr) =1.5×ULN, or creatinine clearance (Ccr) =50 mL/min
(according to Cockcroft and Gault formula); D) Urine routine / 24-hour protein
quantification: qualitative urine protein =1+ (if qualitative urine protein =2+, 24
hours < 1g can be included); E) Cardiac function: left ventricular ejection fraction
=50%; F) Coagulation function: International standardized ratio (INR) =1.5×ULN, and
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, etc.) with their
partner during the trial and for at least 6 months after the last medication;Women of
childbearing age must have a negative blood or urine pregnancy test within 7 days
prior to the first use of the study drug.
Exclusion Criteria:
1. Colorectal cancer patients with HER2 positive (immunohistochemical +++, or
immunohistochemical ++ with FISH amplification);
2. Have received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy
and other anti-tumor therapy within 4 weeks prior to the first use of the study drug,
except the following:
Oral fluorouracil and small molecule targeted drugs are 2 weeks before the first
administration of the study drug or within the 5 half-lives of the drug (whichever is
longer); The traditional Chinese medicines with anti-tumor indications were within 2
weeks before the first use of the study drug;
3. Received an unmarketed clinical investigational drug or treatment within 4 weeks prior
to the first use of the investigational drug;
4. Has undergone major organ surgery (excluding needle biopsy, tracheotomy, gastrostomy,
etc.) or has significant trauma within 4 weeks before the first use of study drugs, or
needs to undergo elective surgery during the trial;
5. Previous recipients of allogeneic hematopoietic stem cell transplantation or organ
transplantation;
6. A history of serious cardiovascular and cerebrovascular diseases, including but not
limited to:
Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias
requiring clinical intervention, grade iii atrioventricular block, etc.
In the resting state, QT interval was prolonged (QTc > 450 msec in men or QTc > 470
msec in women); Acute coronary syndrome, congestive heart failure, aortic dissection,
stroke or other grade 3 or higher cardio-cerebrovascular events within 6 months prior
to the first administration; New York Heart Association (NYHA) heart function grade
=II heart failure;
7. Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus,
inflammatory bowel disease, etc., except type I diabetes, hypothyroidism that can be
controlled only with replacement therapy, and skin diseases that do not require
systemic treatment (e.g., vitiligo, psoriasis);
8. A history of other malignant tumors within 3 years prior to the first administration,
with no signs of recurrence and metastasis;
9. Poorly controlled hypertension (systolic blood pressure & GT;150 mmHg or diastolic
pressure >100 mmHg);
10. Pulmonary disease defined as grade 3 or higher according to CTCAE V5.0;Patients with
past or present interstitial lung disease (ILD);
11. Cerebral parenchymal or meningeal metastases with clinical symptoms are not suitable
for inclusion by the investigator;
12. Had = grade 3 infusion-related reactions during prior anti-EGFR antibody therapy
(Cohort_B only);
13. There are known allergic contraindications to any excipients of SI-B001 and
chemotherapeutic agents selected in this study;
14. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active
hepatitis B virus infection (HBV-DNA copy number > 104) or hepatitis C virus infection
(HCV-RNA > center detection lower limit);
15. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia,
sepsis, etc.;
16. Pregnant or lactating women;
17. Persons with mental disorders or poor compliance;
18. The investigator considers that the subject has a history of other serious systemic
diseases or other reasons and is not suitable to participate in this clinical study.
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