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SI-B001 Combined With Osimertinib Mesylate Tablets in the Treatment of Recurrent Metastatic Non-small Cell Lung Cancer.

Primary Purpose

Non-small Cell Lung Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
SI-B001
Osimertinib
Sponsored by
Sichuan Baili Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring NSCLC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female;
  2. Age: ≥ 18 years;
  3. Expected survival time ≥ 3 months;
  4. Histopathologically and/or cytologically confirmed locally advanced or metastatic NSCLC patients who are enrolled in 3 cohorts:

    A) patients progressed on prior 1st line or 2nd line 3rd generation EGFR-TKI treatment; B) patients progressed on prior 1st line 1st or 2nd generation EGFR-TKI treatment and with T790M negative mutation; C) patients with EGFR exon20ins mutation;

  5. Agree to provide archival tumor tissue samples or fresh tissue samples of the primary tumor or metastases within 6 months; if the subject cannot provide tumor tissue samples, they can be evaluated by the investigator if they meet other inclusion and exclusion criteria;
  6. Must have at least one measurable lesion as defined by RECISTv1.1;
  7. Performance status score ECOG0 or 1;
  8. Toxicities from prior anticancer therapy have recovered to grade ≤ 2 as defined by NCI-CTCAEv5.0 (except alopecia);
  9. No severe cardiac dysfunction, left ventricular score ≥ 50%;
  10. The level of organ function must meet the following criteria:

    1. Bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 80 × 109/L, hemoglobin ≥ 90 g/L;
    2. Liver function: TBIL ≤ 1.5ULN (total bilirubin ≤ 3ULN for subjects with Gilbert's syndrome, liver cancer or liver metastases); AST and ALT ≤ 2.5ULN for subjects without liver metastases; AST and ALT ≤ 5.0ULN for subjects with liver metastases;
    3. Renal function: creatinine (Cr) ≤ 1.5ULN, or creatinine clearance (Ccr) ≥ 50 mL/min (according to CockcroftandGault formula).
  11. Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5ULN;
  12. Urine protein ≤ 2 + (measured by dipstick) or < 1000 mg/24 h (urine);
  13. Premenopausal women of childbearing potential must have a negative serum or urine pregnancy test 7 before starting treatment and must be non-lactating; all patients (male or female) should take adequate barrier contraception measures throughout the treatment cycle and 6 months after the end of treatment.

Exclusion Criteria:

  1. Patients with MET, ALK, RET, HER2 mutations suggested by gene sequencing;
  2. Patients who have previously received systemic chemotherapy in the first/second line of systemic therapy;
  3. Use chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery before the first dose;
  4. History of significant cardiac disease, such as: symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE 5.0) history, New York Heart Association (NYHA) ≥ grade 2 heart failure, acute coronary syndrome, etc.; QT prolongation (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, third degree atrioventricular block;
  5. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, except for type I diabetes, hypothyroidism controllable by replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis);
  6. Other malignancies diagnosed within 5 years prior to first dose, Exceptions include: radical basal cell carcinoma of the skin, scaly cell carcinoma of the skin, and/or radical resection of carcinoma in situ;
  7. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);
  8. Pulmonary disease defined as ≥ grade 3 according to CTCAEv5.0, including resting dyspnea, or requiring continuous oxygen therapy, or patients with a history of interstitial lung disease (ILD);
  9. Symptoms of active central nervous system metastases.However, patients with stable parenchymal metastases can be stable, and whether it is stable or not is judged by the investigator;
  10. Patients with a history of hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies or hypersensitivity to SI-B001 or any of the excipient components of Osimertinib;
  11. History of autologous or allogeneic stem cell transplantation;
  12. In previous anthracycline (neo) adjuvant therapy, the cumulative dose of anthracycline was > 360 mg/m2;
  13. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 104) or hepatitis C virus (HCV) infection;
  14. Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
  15. Received other unmarketed clinical study drugs or treatments before participating in the study;

Sites / Locations

  • The Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting
  • The Second Affiliated Hospital of Guilin Medical UniversityRecruiting
  • Sun Yat-sen University Cancer Center (SYSUCC)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

SI-B001 combined with osimertinib_A

SI-B001 combined with osimertinib_B

SI-B001 combined with osimertinib_C

Arm Description

Patients with locally advanced/metastatic NSCLC progressed on 3rd generation EGFR-TKI treatment.

Patients with locally advanced/metastatic NSCLC progressed on prior EGFR-TKI treatment and with T790M negative mutation.

Patients with locally advanced/metastatic NSCLC and with EGFR exon20ins mutation.

Outcomes

Primary Outcome Measures

ORR
Objective Response Rate
Optimal combination dose (only Phase IIa)
Optimal combination dose for SI-B001 and Osimertinib (only IIa)

Secondary Outcome Measures

PFS
Progression-free Survival
DCR
Disease Control Rate
DOR
Duration of Response
TEAE
Treatment Emergent Adverse Events
Cmax
Maximum serum concentration
Tmax
Time to maximum serum concentration
Ctrough
Minimum serum concentration
ADA
anti-SI-B001 antibody

Full Information

First Posted
August 22, 2021
Last Updated
May 5, 2023
Sponsor
Sichuan Baili Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05020769
Brief Title
SI-B001 Combined With Osimertinib Mesylate Tablets in the Treatment of Recurrent Metastatic Non-small Cell Lung Cancer.
Official Title
A Phase II/III Clinical Study to Evaluate the Efficacy and Safety of SI-B001 in Combination With Osimertinib Mesylate Tablets in the Treatment of Recurrent and Metastatic Non- Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 6, 2022 (Actual)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
June 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sichuan Baili Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This multi-center, open label Phase II/III clinical study is performed in patients with locally advanced/metastatic NSCLC progressed on prior EGFR-TKI treatment or with non TKI-sensitizing mutation or patients with EGFR exon20ins mutation. This study is investigating the safety and efficacy of SI-B001 at monotherapy RP2D or lower combined with Osimertinib in patients with locally advanced or metastatic NSCLC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SI-B001 combined with osimertinib_A
Arm Type
Experimental
Arm Description
Patients with locally advanced/metastatic NSCLC progressed on 3rd generation EGFR-TKI treatment.
Arm Title
SI-B001 combined with osimertinib_B
Arm Type
Experimental
Arm Description
Patients with locally advanced/metastatic NSCLC progressed on prior EGFR-TKI treatment and with T790M negative mutation.
Arm Title
SI-B001 combined with osimertinib_C
Arm Type
Experimental
Arm Description
Patients with locally advanced/metastatic NSCLC and with EGFR exon20ins mutation.
Intervention Type
Drug
Intervention Name(s)
SI-B001
Intervention Description
SI-B001 is administered by intravenous drip once weekly (QW). 120 min ± 10 min after the first intravenous drip, if the infusion reaction is tolerable during the first dose, the subsequent infusion can be completed within 60-120 min (unless agreed or required by the investigator, the infusion time can be extended).
Intervention Type
Drug
Intervention Name(s)
Osimertinib
Intervention Description
Osimertinib is administered at the recommended dose of 80mg daily.
Primary Outcome Measure Information:
Title
ORR
Description
Objective Response Rate
Time Frame
Up to approximately 24 months
Title
Optimal combination dose (only Phase IIa)
Description
Optimal combination dose for SI-B001 and Osimertinib (only IIa)
Time Frame
Up to approximately 24 months
Secondary Outcome Measure Information:
Title
PFS
Description
Progression-free Survival
Time Frame
Up to approximately 24 months
Title
DCR
Description
Disease Control Rate
Time Frame
Up to approximately 24 months
Title
DOR
Description
Duration of Response
Time Frame
Up to approximately 24 months
Title
TEAE
Description
Treatment Emergent Adverse Events
Time Frame
Up to approximately 24 months
Title
Cmax
Description
Maximum serum concentration
Time Frame
Up to approximately 24 months
Title
Tmax
Description
Time to maximum serum concentration
Time Frame
Up to approximately 24 months
Title
Ctrough
Description
Minimum serum concentration
Time Frame
Up to approximately 24 months
Title
ADA
Description
anti-SI-B001 antibody
Time Frame
Up to approximately 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Voluntarily sign the informed consent and follow the requirements of the protocol; Male or female; Age: ≥ 18 years; Expected survival time ≥ 3 months; Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) confirmed by histopathology and/or cytology, T790M-negative, Exon20ins mutation resistant to the third generation EGFR TKI after the first or second line treatment, or resistance to the first or second generation TKI after the first line treatment; Consent to provide an archived tumor tissue specimen or fresh tissue sample (an FFPE block or approximately 6-12 white slides with a size of 5μm) from the primary or metastatic tumor within 6 months of the date of consent. Participants who were unable to provide tumor tissue samples could be enrolled if they met other inclusion and exclusion criteria after evaluation by investigators. Must have at least one measurable lesion as defined by RECISTv1.1; Performance status score ECOG0 or 1; Toxicity from previous antineochemical therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 (asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose were considered by the investigator, and toxicity with no safety risk was judged by the investigator; Except for alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacement therapy). No severe cardiac dysfunction, left ventricular score ≥ 50%; The level of organ function must meet the following criteria: Bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelet count ≥ 80 × 10^9/L, hemoglobin ≥ 90 g/L; Liver function: TBIL ≤ 1.5ULN (total bilirubin ≤ 3ULN for subjects with Gilbert's syndrome, liver cancer or liver metastases); AST and ALT ≤ 2.5ULN for subjects without liver metastases; AST and ALT ≤ 5.0ULN for subjects with liver metastases; Renal function: creatinine (Cr) ≤ 1.5ULN, or creatinine clearance (Ccr) ≥ 50 mL/min (according to CockcroftandGault formula). Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5ULN; Urine protein ≤ 2 + (measured by dipstick) or < 1000 mg/24 h (urine); Premenopausal women of childbearing potential must have a negative serum or urine pregnancy test 7 before starting treatment and must be non-lactating; all patients (male or female) should take adequate barrier contraception measures throughout the treatment cycle and 6 months after the end of treatment. Exclusion Criteria: Gene sequencing showed that there were MET, ALK, RET, HER2 and other driver gene mutations related to the occurrence and development of tumors. Patients with prior systemic chemotherapy as part of first - or second-line systemic therapy; Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, and major surgery were used within 4 weeks before the first dose, and palliative radiotherapy, targeted therapy (including small molecule tyrosine kinase inhibitors), and other anti-tumor treatments were used within 2 weeks before the first dose. The history of severe heart disease within the past six months was screened, such as symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE v5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, acute coronary syndrome, etc. Prolonged QT interval (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, atrioventricular block III degree; Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory intestinal diseases and Hashimoto's thyroiditis, etc., excluding type I diabetes mellitus, hypothyroidism that can be controlled only by replacement therapy, and skin diseases without systemic treatment (such as vitiligo and psoriasis); Other malignant tumors diagnosed within 5 years before the first dose of treatment, except those with radical basal cell carcinoma, squamous cell carcinoma of the skin, and/or radical resection in situ carcinoma considered by investigators to be eligible; Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg); Pulmonary disease grade ≥3 was defined according to CTCAE v5.0, including dyspnea at rest, or requiring continuous oxygen therapy, or a history of interstitial lung disease (ILD). There were symptoms of active central nervous system metastasis. However, patients with stable parenchymal metastases could be enrolled, and whether they were stable was defined by the investigators. Patients with a history of allergy to the recombinant humanized or human-mouse chimeric antibody or to SI-B001 or any of the excipients of the chemotherapeutic agents used in this trial; A history of autologous or allogeneic stem cell transplantation; The cumulative dose of anthracyclines in previous (new) adjuvant therapy was > 360 mg/m^2; Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 10^4) or hepatitis C virus infection (HCV-RNA > the lower limit of detection in the research center); Active infections requiring systemic therapy, such as severe pneumonia, bacteremia, sepsis, etc.; Received other unmarketed investigational drugs or treatments within 4 weeks before study enrollment; Other conditions for trial participation were not considered by the investigator to be appropriate
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hai Zhu
Phone
+86-13980051002
Email
zhuhai@baili-pharm.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sa Xiao, PhD
Phone
+86-15013238943
Email
xiaosa@baili-pharm.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Li Zhang
Organizational Affiliation
Sun Yat-sen University Cancer Center (SYSUCC)
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiaquan Fan
Facility Name
The Second Affiliated Hospital of Guilin Medical University
City
Guilin
State/Province
Guangxi Zhuang Autonomous Region
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bihui Li
Facility Name
Sun Yat-sen University Cancer Center (SYSUCC)
City
Guangdong
State/Province
Guangzhou
ZIP/Postal Code
510075
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Zhang
Phone
020-87343458
Email
zhangli6@mail.sysu.edu.cn

12. IPD Sharing Statement

Learn more about this trial

SI-B001 Combined With Osimertinib Mesylate Tablets in the Treatment of Recurrent Metastatic Non-small Cell Lung Cancer.

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