Clinical trial NCT04603287: A Study of SI-B001, an EGFR/HER3 Bispecific Antibody, in Locally Advanced or Metastatic Epithelial Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of SI-B001, an EGFR/HER3 Bispecific Antibody, in Locally Advanced or Metastatic Epithelial Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Epithelial Tumor
Keywords: Non-small cell lung cancer (NSCLC)
Head and neck squamous cell carcinoma (HNSCC)
Esophageal cancer
Colorectal cancer
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: SystImmune Inc.
First posted: 2020-10-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: In phase Ia study, the safety and tolerability of SI-B001 in patients with locally advanced or metastatic epithelial malignancies will be investigated to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) of SI-B001.

In the phase Ib study, the safety and tolerability of SI-B001 at the phase Ia recommended dose will be further investigated, and recommended phase II dose (RP2D) for phase II clinical studies will be determined.

In addition, the preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of SI-B001 in patients with locally advanced or metastatic epithelial tumors will be evaluated.


Eligibility criteria: Inclusion Criteria:

1. Participants must sign the informed consent form voluntarily and follow the plan requirements.
2. No gender limit.
3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib).
4. Expected survival time ≥ 3 months.
5. Locally advanced or metastatic epithelial malignancies are confirmed by histopathology and/or cytology that are incurable or currently without standard treatment.
6. Participants must agree to provide archived tumor tissue specimens or fresh tissue samples within 6 months of the primary tumor or metastasis; in phase Ia, if the participant is unable to provide tumor tissue samples, the investigator will evaluate whether the participant could be enrolled if other criteria are fit to join the group.
7. Participants must have at least one measurable lesion that meets the definition of RECIST v1.1.
8. Physical fitness score ECOG 0 or 1 point.
9. The toxicity of previous anti-tumor treatments has been restored to NCI-CTCAE v5.0 definition ≤ 1 (except for hair loss).
10. No serious cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%, (hypersensitivity) troponin T\<ULN.
11. The organ function must meet the following requirements and standards: a) Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥90 g/L; B) Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN for participants without liver metastasis, AST and ALT ≤5.0 ULN for liver metastases; c) Kidney function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to the Cockcroft and Gault formula).
12. Coagulation function: International normalized ratio (INR)≤1.5×ULN, and activated partial thromboplastin time (APTT)≤1.5ULN.
13. Urine protein≤2%2B (measured with test paper) or≤1000mg/24h (urine).
14. For premenopausal women with childbearing potential, a pregnancy test must be taken within 7 days prior to the start of treatment. Serum or urine pregnancy must be negative and must be non-lactating; all participants (regardless of male or female) in the group should be treated throughout the treatment. Adequate barrier contraceptive measures should be taken during the treatment and 6 months after the treatment.

Exclusion Criteria:

1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2weeks prior to the first administration.
2. If there is a history of vaccination within 3 months prior to the first administration, it is allowed to receive inactivated influenza vaccine within 30 days prior to the first administration, and the treatment of live attenuated vaccine is not allowed.
3. Participants with history of severe heart disease, such as: symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, history of transmural myocardial infarction, unstable angina pectoris etc.
4. Participants with prolonged QT interval (male QTc\> 450 msec or female QTc\> 470 msec), complete left bundle branch block, III grade 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, etc., except for type I diabetes, hypothyroidism that can be controlled only by alternative treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis).
6. Other malignant tumors were diagnosed within 5 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection.
7. Participants with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure\>150 mmHg or diastolic blood pressure\>100 mmHg).
8. Participants have grade 3 lung disease defined according to NCI-CTCAE v5.0, including participants with resting dyspnea, or requiring continuous oxygen therapy, or a history of interstitial lung disease (ILD).
9. Symptoms of active central nervous system metastasis. However, participants with stable brain metastasis or stable epidural spinal cord compression history can be included. Stable is defined as: a. With or without antiepileptic drugs, the seizure-free state lasts for more than 12 weeks; b. There is no need to use glucocorticoids; c. Continuous multiple MRI (scanning interval at least 8 weeks) showed a stable state in imaging.
10. Participants who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of SI-B001.
11. Participants have a history of autologous or allogeneic stem cell transplantation.
12. In the adjuvant (or neoadjuvant) treatment of anthracyclines, the cumulative dose of anthracyclines is\> 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. Participants with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
15. Other conditions that the investigator believes that it is not suitable for participating in this clinical trial.
16. Participated in another clinical trial within 4 weeks prior to participating in the study.

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to 28 days after the first dose of SI-B001
measure: Phase Ia: Maximum tolerated dose (MTD)
timeFrame: Up to 28 days after the first dose of SI-B001
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to 28 days after the first dose of SI-B001
Secondary outcomes:
measure: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to 28 days after the first dose of SI-B001
measure: Tmax
timeFrame: Up to 28 days after the first dose of SI-B001
measure: T1/2
timeFrame: Up to 28 days after the first dose of SI-B001
measure: AUC0-t
timeFrame: Up to 28 days after the first dose of SI-B001
measure: CL (Clearance)
timeFrame: Up to 28 days after the first dose of SI-B001
measure: Ctrough
timeFrame: Up to 28 days after the first dose of SI-B001
measure: ADA (anti-drug antibody)
timeFrame: Up to approximately 24 months
measure: Nab (neutralizing antibody)
timeFrame: Up to approximately 24 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 24 months
measure: Overall survival
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Chengdu
country: China
facility: West China Hospital，Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Sun Yat-sen University
name: Li Zhang
role: PRINCIPAL_INVESTIGATOR
References: