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

NCT05039944 | Terminated Phase 2

• 1 other identifier: SI-B001_211
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Keywords

CRC

Outcome Measures

Primary Outcomes (2)

• ORR

  Objective Response Rate

  Up to approximately 24 months

• Optimal combination dose (only IIa)

  Optimal combination dose of SI-B001 with chemothreapy (only IIa)

  Up to approximately 24 months

Secondary Outcomes (9)

• PFS

  Up to approximately 24 months

• DCR

  Up to approximately 24 months

• DOR

  Up to approximately 24 months

• OS

  Up to approximately 24 months

• TEAE

  Up to approximately 24 months

Study Arms (6)

SI-B001_A

EXPERIMENTAL

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).

Drug: SI-B001

SI-B001_B

EXPERIMENTAL

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).

Drug: SI-B001

SI-B001_C

EXPERIMENTAL

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).

Drug: SI-B001

SI-B001 combined with irinetecan_D

EXPERIMENTAL

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).

Drug: SI-B001; Drug: Irinotecan

SI-B001 combined with FOLFIRI or FOLFOX_E

EXPERIMENTAL

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).

Drug: SI-B001; Drug: FOLFIRI Protocol; Drug: FOLFOX Protocol

SI-B001 combined with irinetecan_F

EXPERIMENTAL

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).

Drug: SI-B001; Drug: Irinotecan

Interventions

SI-B001 DRUG

In Arm\_A, B and C, the intravenous infusion dose of SI-B001 was single drug RP2D selected in phase I (Q2W); In Cohort\_D, E, and F, SI-B001 was divided into two doses, the high dose was the single drug RP2D selected in phase I clinical trial, and the low dose was the second low dose of single drug RP2D, both of which were administered by intravenous infusion.

SI-B001 combined with FOLFIRI or FOLFOX_E; SI-B001 combined with irinetecan_D; SI-B001 combined with irinetecan_F; SI-B001_A; SI-B001_B; SI-B001_C

Irinotecan DRUG

Administration by intravenous infusion, 180 mg/m2 Q2W.

SI-B001 combined with irinetecan_D; SI-B001 combined with irinetecan_F

FOLFIRI Protocol DRUG

FOLFIRI is administered intravenously at the standard dose recommended by the guidelines(Q2W).

SI-B001 combined with FOLFIRI or FOLFOX_E

FOLFOX Protocol DRUG

FOLFOX is administered intravenously at the standard dose recommended by the guidelines(Q2W).

SI-B001 combined with FOLFIRI or FOLFOX_E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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;
• There must be at least one measurable lesion conforming to the RECIST V1.1 definition;
• Cohort\_A, B, C fitness scores ≤2, Cohort\_D, E, F fitness scores ≤1;
• 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);
• Organ function levels must meet the following requirements and meet the following standards:

You may not qualify if:

• 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);
• A history of other malignant tumors within 3 years prior to the first administration, with no signs of recurrence and metastasis;
• Poorly controlled hypertension (systolic blood pressure \& GT;150 mmHg or diastolic pressure \>100 mmHg);
• Pulmonary disease defined as grade 3 or higher according to CTCAE V5.0;Patients with past or present interstitial lung disease (ILD);
• Had ≥ grade 3 infusion-related reactions during prior anti-EGFR antibody therapy (Cohort\_B only);
• There are known allergic contraindications to any excipients of SI-B001 and chemotherapeutic agents selected in this study;

Sponsors & Collaborators

• Sichuan Baili Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; IFL protocol; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Weijian Guo

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2021
• First Posted: September 10, 2021
• Study Start: November 30, 2021
• Primary Completion: June 6, 2022
• Study Completion: June 6, 2022
• Last Updated: July 18, 2024

Record last verified: 2024-07

Locations

CN (1)