Clinical trial NCT05044897: A Clinical Study to Evaluate the Efficacy and Safety of SI-B001 in the Treatment of Recurrent and Metastatic HNSCC
Official title: A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B001 in the Treatment of Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: HNSCC
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-16
Enrollment: 30
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: This multi-center, open label phase II clinical study is performed in patients with recurrent metastatic squamous cell carcinoma of the head and neck progressed on prior anti-PD-1 mab ± platinum-based chemotherapy. This study is investigating the safety and efficacy of SI-B001 as a single agent in patients.


Eligibility criteria: Inclusion Criteria:

1. Sign the informed consent voluntarily and comply with the requirements of the program;
2. Age ≥18; Gender is not limited;
3. Expected survival time ≥3 months;
4. Locally advanced squamous cell carcinoma of the head and neck confirmed by histology or pathology as recurrent metastatic or without indications of radical local treatment;
5. Patients who failed or were intolerant to previous anti-PD-1 mab and platinum-containing chemotherapy

   * Treatment failure of PD-1 refers to disease progression during or after PD-1 treatment.
   * Failure of platinum-containing chemotherapy refers to:

     1. disease progression during or after platinum-containing chemotherapy;
     2. recurrence or disease progression within 6 months of platinum-containing multi-mode therapy;
6. Agree to provide tumor tissue samples (FFPE block or 10 unstained sections of 5μm size) or fresh tissue samples archiving within one year from primary or metastatic foci. If the patient fails to provide the samples, they can be included after the investigator's judgment;
7. There must be at least one measurable lesion in accordance with the RECIST v1.1 definition. Tumor lesions located in the area of previous radiotherapy or other local regional treatment sites are generally not measurable unless there is definite progression of the lesion or the lesion persists three months after radiotherapy;
8. Physical fitness ECOG score 0 or 1;
9. Adverse reactions to previous antitumor therapy were restored to CTCAE 5.0 ≤1 (except for toxicity judged by the researchers to be of no safety risk, such as hair loss, grade 2 peripheral neurotoxicity, and stable hypothyroidism after hormone replacement therapy);
10. Organ function levels must meet the following requirements and meet the following standards:

    1. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×10\*9/L, platelet count ≥75×10\*9/L, hemoglobin ≥90 g/L;
    2. Liver function: Total bilirubin TBIL≤1.5×ULN (total bilirubin ≤3×ULN in Subjects with Gilbert's syndrome, liver cancer or liver metastasis), AST and ALT ≤2.5×ULN in patients without liver metastasis, AST and ALT ≤5.0×ULN in patients with liver metastasis;
    3. Renal function: creatinine (Cr) ≤1.5×ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula);
    4. Urine routine / 24-hour protein quantification: qualitative urine protein ≤1+ (if qualitative urine protein ≥2+, 24-hour protein \< 1g can be included in the group);
    5. Cardiac function: left ventricular ejection fraction ≥50%;
    6. Coagulation function: International standardized ratio (INR) ≤1.5×ULN, and activated partial thrombin time (APTT) ≤1.5×ULN;
11. Eligible fertile patients (male and female) must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence, etc.) with their partner during the trial period 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. Squamous cell carcinoma with primary site of nasopharynx or skin;
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:

   * Nitrosorea or mitomycin C within 6 weeks before the first administration of the study drug;
   * 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 diseases and inflammatory diseases, such as: systemic lupus erythematosus, systemic treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and hashimoto's thyroiditis, etc., with the exception of type I diabetes, only replacement therapy can control the hypothyroidism, no systemic treatment of skin disease (e.g., vitiligo, psoriasis);
8. A history of other malignancies within 5 years prior to first administration, except for radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or radical excised carcinoma in place, and second primary squamous cell carcinoma of the head and neck;
9. Poorly controlled hypertension (systolic blood pressure \& GT; 150 mmHg or diastolic pressure \&gt; 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. Experienced ≥ grade 3 infusion-related reactions during previous anti-EGFR antibody therapy;
13. 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);
14. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
15. Pregnant or lactating women;
16. Persons with mental disorders or poor compliance;
17. 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

Primary outcomes:
measure: ORR
timeFrame: Up to 2 weeks
Secondary outcomes:
measure: DOR
timeFrame: Up to 2 years
measure: PFS
timeFrame: Up to 2 years
measure: DCR
timeFrame: Up to 2 years
measure: OS
timeFrame: Up to 2 years
measure: TEAE
timeFrame: Up to 2 years
measure: Tmax
timeFrame: Up to 2 years
measure: Cmax
timeFrame: Up to 2 years
measure: Ctrough
timeFrame: Up to 2 years
measure: ADA
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Guilin
country: China
facility: The Second Affiliated Hospital of Guilin Medical University
state: Guangxi Zhuang Autonomous Region
city: Guiyang
country: China
facility: The Affiliated Cancer Hospital of Guizhou Medical University
state: Guizhou
city: Shanghai
country: China
facility: Shanghai Oriental Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Oriental Hospital
name: Ye Guo
role: PRINCIPAL_INVESTIGATOR
References: