Efficacy and Safety of SI-B001 as a Single Agent or in Combination With Chemotherapy in the Treatment of Digestive System Malignancies

• Status: Not yet recruiting
• Trial end date: 2023-09-20
• Target enrollment: 0
• Participant gender: All

Summary

1. Evaluation of effectiveness: To further evaluate the effectiveness of SI-B001 monotherapy RP2D in patients with unresectable or metastatic colorectal cancer and gastric cancer;To evaluate the efficacy of SI-B001 RP2D and sublow dose combined with chemotherapy in patients with unresectable or metastatic colorectal cancer；

2. Evaluation of safety and tolerability: To further evaluate the safety and tolerability of SI-B001 single-agent RP2D in patients with unresectable or metastatic colorectal cancer and gastric cancer;To evaluate the safety and tolerability of SI-B001 RP2D and sublow dose combined with chemotherapy in patients with unresectable or metastatic colorectal cancer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Treatments: Irinotecan

Criteria

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.