A Clinical Study of SI-B001 in Combination With Paclitaxel/Docetaxel in the Treatment of Recurrent and Metastatic HNSCC

A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B001 in Combination With Paclitaxel/Docetaxel in the Treatment of Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck

This Phase IIa study is a clinical trial to evaluate the safety and efficacy of SI-B001 in combination with paclitaxel or docetaxel in patients with recurrent or metastatic head and neck squamous cell carcinoma (non-nasopharyngeal carcinoma) who have experienced disease progression or intolerance to prior anti-PD-1 monoclonal antibody therapy with or without platinum-based chemotherapy, and who have received no more than second-line treatment.

Inclusion Criteria:

1. The participants could understand and sign the informed consent form and must participate voluntarily.

2. No gender limit;

3. Age: ≥18 years old

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 have failed or are intolerant to prior anti-PD-1 monotherapy ± platinum-based chemotherapy; Cohort-A: Patients with recurrent/metastatic head and neck squamous cell carcinoma (non-nasopharyngeal carcinoma) who have progressed on or are intolerant to first-line anti-PD-1/PD-L1 antibody ± platinum-based doublet chemotherapy, receiving SI-B001 in combination with paclitaxel/docetaxel in the second-line setting (patients with no prior treatment with docetaxel, paclitaxel, nab-paclitaxel, or paclitaxel liposome receive paclitaxel in combination; patients with prior docetaxel treatment receive paclitaxel in combination; patients with prior treatment with paclitaxel, nab-paclitaxel, or paclitaxel liposome receive docetaxel in combination).

   Cohort-B: Patients with recurrent/metastatic head and neck squamous cell carcinoma (non-nasopharyngeal carcinoma) who have progressed on or are intolerant to first-line platinum-based doublet chemotherapy ± EGFR monoclonal antibody, and subsequently progressed on or are intolerant to second-line anti-PD-1/PD-L1 monoclonal antibody-containing therapy, receiving SI-B001 in combination with paclitaxel/docetaxel in the third-line setting (patients with no prior treatment with docetaxel, paclitaxel, nab-paclitaxel, or paclitaxel liposome receive paclitaxel in combination; patients with prior docetaxel treatment receive paclitaxel in combination; patients with prior treatment with paclitaxel, nab-paclitaxel, or paclitaxel liposome receive docetaxel in combination).

6. Previously received only ≤ 2-line treatment for recurrent and metastatic squamous cell carcinoma of the head and neck;

7. Agree to provide tumor tissue samples (FFPE block or 10 unstained sections of 5μm size) or fresh tissue samples that have been archival within 1 year of primary or metastatic lesion. If the patient fails to provide them, they can be included after the investigator's judgment;

8. 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;

9. Physical fitness ECOG score 0 or 1;

10. Toxicity of previous antitumor therapy has returned to ≤1 as defined by NCI-CTCAE V5.0 (except for toxicity that the investigators judged to be of no safety risk, such as hair loss, grade 2 peripheral neurotoxicity, and stabilized hypothyroidism after hormone replacement therapy);

11. 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 ≥100×10*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;

12. Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence, etc.) with their partner during the trial 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 of primary origin in the nasopharynx, salivary glands, paranasal sinuses, skin, or of unknown primary site;

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. Patients who have previously been treated with paclitaxel, nab-paclitaxel, liposomal paclitaxel, or docetaxel;

6. Previous recipients of allogeneic hematopoietic stem cell transplantation or organ transplantation;

7. 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 grades 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;

8. 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 hypothyroidism, no systemic treatment of skin disease (e.g., vitiligo, psoriasis);

9. 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;

10. Poorly controlled hypertension (systolic blood pressure & GT; 150 mmHg or diastolic pressure > 100 mmHg);

11. Pulmonary disease defined as grade 3 or higher according to CTCAE V5.0; Patients with past or present interstitial lung disease (ILD);

12. Cerebral parenchymal or meningeal metastases with clinical symptoms are not suitable for inclusion by the investigator;

13. Experienced ≥ grade 3 infusion-related reactions during previous anti-EGFR antibody therapy;

14. Known allergies to paclitaxel or its standard pretreatments or other contraindications to products containing castor oil;

15. 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);

16. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;

17. Pregnant or lactating women;

18. Persons with mental disorders or poor compliance;

19. 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.