A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B001 as a Single Agent or in Combination With Chemotherapy in the Treatment of Unresectable or Metastatic Digestive System Malignancies (Colorectal and Gastric Cancer)
Overview
- Phase
- Phase 2
- Intervention
- SI-B001
- Conditions
- Colorectal Cancer
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- Optimal combination dose (only IIa)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This multi-center, open label Phase II clinical study is performed in patients with unresectable or metastatic malignant tumors of the digestive system (colorectal cancer, gastric cancer). This study is investigating the safety and efficacy of SI-B001 at monotherapy or optimal combination dose with chemotherapy in patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, age ≥18;
- •Expected survival time ≥3 months;
- •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.
- •No previous anti-EGFR antibody therapy (excluding Cohort_B);
Exclusion Criteria
- •Colorectal cancer patients with HER2 positive (immunohistochemical +++, or immunohistochemical ++ with FISH amplification);
- •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;
- •Received an unmarketed clinical investigational drug or treatment within 4 weeks prior to the first use of the investigational drug;
- •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;
- •Previous recipients of allogeneic hematopoietic stem cell transplantation or organ transplantation;
- •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;
- •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);
Arms & Interventions
SI-B001_A
Patients with unresectable or metastatic gastric cancer, HER2-negative and without standard treatment were treated with SI-B001 monotherapy.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: SI-B001
SI-B001_B
Patients with MSS KRASwt BRAFwt unresectable or metastatic colorectal cancer who had failed conventional chemotherapy combined with EGFR mab were treated with SI-B001 monotherapy.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: SI-B001
SI-B001_C
Patients with MSS KRASwt BRAFwt unresectable or metastatic colorectal cancer who had failed multiple lines of conventional chemotherapy (excluding EGFR monoclonal antibody) were treated with SI-B001 monotherapy.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: SI-B001
SI-B001 combined with irinetecan_D
Patients with MSI-H KRASwt BRAFwt unresectable or metastatic colorectal cancer who had previously failed to receive anti-PD-1 (L1) mab (excluding EGFR mab) in the first or second line were treated with SI-B001 in combination with irinetecan in the third line.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: SI-B001
SI-B001 combined with irinetecan_D
Patients with MSI-H KRASwt BRAFwt unresectable or metastatic colorectal cancer who had previously failed to receive anti-PD-1 (L1) mab (excluding EGFR mab) in the first or second line were treated with SI-B001 in combination with irinetecan in the third line.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: Irinotecan
SI-B001 combined with FOLFIRI or FOLFOX_E
Patients with MSI-H KRASwt BRAFwt unresectable or metastatic colorectal cancer who had previously failed first-line anti-PD-1 (L1) mab were treated with SI-B001 in combination with FOLFIRI or FOLFOX for second-line treatment.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: SI-B001
SI-B001 combined with FOLFIRI or FOLFOX_E
Patients with MSI-H KRASwt BRAFwt unresectable or metastatic colorectal cancer who had previously failed first-line anti-PD-1 (L1) mab were treated with SI-B001 in combination with FOLFIRI or FOLFOX for second-line treatment.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: FOLFIRI Protocol
SI-B001 combined with FOLFIRI or FOLFOX_E
Patients with MSI-H KRASwt BRAFwt unresectable or metastatic colorectal cancer who had previously failed first-line anti-PD-1 (L1) mab were treated with SI-B001 in combination with FOLFIRI or FOLFOX for second-line treatment.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: FOLFOX Protocol
SI-B001 combined with irinetecan_F
Patients with MSS KRASwt BRAFwt unresectable or metastatic colorectal cancer who had failed standard first-line treatment containing oxaliplatin or irinotecan plus fluorouracil plus or minus bevacizumab were treated with SI-B001 plus irinotecan in the second-line.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: SI-B001
SI-B001 combined with irinetecan_F
Patients with MSS KRASwt BRAFwt unresectable or metastatic colorectal cancer who had failed standard first-line treatment containing oxaliplatin or irinotecan plus fluorouracil plus or minus bevacizumab were treated with SI-B001 plus irinotecan in the second-line.SI-B001 is administered by intravenous drip twice weekly (Q2W).
Intervention: Irinotecan
Outcomes
Primary Outcomes
Optimal combination dose (only IIa)
Time Frame: Up to approximately 24 months
Optimal combination dose of SI-B001 with chemothreapy (only IIa)
ORR
Time Frame: Up to approximately 24 months
Objective Response Rate
Secondary Outcomes
- Ctrough(Up to approximately 24 months)
- DOR(Up to approximately 24 months)
- TEAE(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- OS(Up to approximately 24 months)
- PFS(Up to approximately 24 months)
- DCR(Up to approximately 24 months)
- ADA(Up to approximately 24 months)