Clinical trial NCT05552807: SCT200 in Combination With SCT-I10A/Paclitaxel/Docetaxel in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Official title: A Multicenter, Open Phase Ib Study to Evaluate the Efficacy and Safety of SCT-I10A in Combination With SCT200 or SCT200 in Combination With Paclitaxel/Docetaxel in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Head and Neck Squamous Carcinoma
Keywords: Carcinoma, Squamous Cell
Lead sponsor: Sinocelltech Ltd.
Sponsor class: INDUSTRY
First posted: 2022-09-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is to explore the efficacy and safety of SCT200 with SCT-I10A or SCT200 combined with paclitaxel/docetaxel in the treatment of recurrent/metastatic head and neck squamous cell carcinoma.

Detailed description: This multicenter, open phase Ib study focused on evaluating the objective response response rates of SCT200 in combination with SCT-I10A or SCT200 in combination with paclitaxel/docetaxel in patients with recurrent/metastatic head and neck squamous cell carcinoma who had previously received different treatments.

Eligibility criteria: Inclusion Criteria:

1. Subjects voluntarily signed a written informed consent prior to screening;
2. Male or female, age ≥ 18 years old;
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
4. Has histologically or cytologically confirmed head and neck squamous cell carcinoma;
5. Recurrent and/or metastatic HNSCC without indications for local radical treatment; Cohort 1: Patients who have received previous platinum-based therapy and experienced disease progression or toxic intolerance during or after treatment; Cohort 2: Patients who have received prior platinum-based therapy and immune checkpoint inhibitors and experienced disease progression or toxic intolerance during or after treatment; Cohort 3: Patients who have not received prior systemic chemotherapy but can receive chemotherapy as part of a multimodality treatment for patients with locally advanced HNSCC;
6. According to RECIST 1.1, there is at least one measurable lesion, for lesions previously treated with radiotherapy, may be selected as a target lesion only if the lesion has shown definite disease progression or persists more than 3 months after the end of radiotherapy;
7. The estimated survival period is ≥ 3 months;
8. Laboratory inspection: Blood test: neutrophils ≥1.5×10\^9/L, hemoglobin ≥90g/L, platelets ≥75×10\^9/L for cohort 1 and cohort 3, and platelets ≥100×10\^9/L for cohort 2; liver function: Serum alanine transaminase (ALT) and serum aspartate aminotransferase (AST), ALT and AST ≤ 3 × ULN for those without liver metastases, ALT and AST ≤ 5 × ULN for those with liver metastases; total bilirubin (TBIL) ≤ 1.5 × ULN (Gilbert syndrome patients, ≤ 3 × ULN); Renal function: serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (Ccr) ≥ 50 ml/min; Coagulation: activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) ≤ 1.5×ULN; Cardiac echocardiography: left ventricular ejection fraction (LVEF) ≥ 50%; Men and women of childbearing potential must agree that they must use contraception during the study period and for 6 months after the last study treatment; have a negative blood pregnancy test within 7 days prior to study enrollment and must non-breastfeeding

Exclusion Criteria:

1. Patients suitable for local radical treatment;
2. Histologically or cytologically confirmed nasopharyngeal or cutaneous squamous carcinoma;
3. Cohorts 1 and 3 previously treated with immune checkpoint inhibitors or treated with EGFR monoclonal antibodies (Immune-checkpoint inhibitors or EGFR monoclonal antibodies as multimodal therapy for locally advanced HNSCC were eligible if the last treatment was more than 6 months after disease progression);
4. Cohort 2 previously received EGFR monoclonal antibody (EGFR monoclonal antibodies as multimodal therapy for locally advanced HNSCC were eligible if the last treatment was more than 6 months after disease progression);
5. Cohort 2 previously received paclitaxel, albumin paclitaxel or paclitaxel liposomes, and received docetaxel, and both of these drugs failed to treat;
6. Previous immunotherapy with grade ≥3 irAE or grade ≥2 immune-associated myocarditis;
7. Other malignant neoplasm present within 5 years or concurrent with the current period, except cured cervical carcinoma in situ, non-melanoma skin cancer or other radically treated tumor/cancer with no signs of disease for at least 5 years;
8. Known peripheral neuropathy ≥ grade 2 according to the Common Terminology Criteria forAdverse Events(CTCAE v5.0) published by the National Cancer Institute (NCI);
9. Active central nervous system (CNS) metastases and/or carcinomatous meningitis;subjects with previously treated brain metastases may be enrolled in the study provided they are clinically stable for at least 2 weeks, have no evidence of new or expanding brain metastases, and have discontinued steroids at least 14 days prior to study drug administration. Stable brain metastases in this definition should be determined before the first dose of study drug. Subjects with asymptomatic brain metastases (i.e., no neurological symptoms, no need for corticosteroids, and no lesions \>1.5 cm) may participate, but require periodic brain imaging at the the tumor lesion ;;
10. Subjects (except alopecia and hypothyroidism stabilized by hormone replacement therapy) who have not recovered from any toxicity and/or complications of previous surgery, chemotherapy or radiotherapy, i.e., who have not dropped to ≤ grade 1 (NCI CTCAE v5.0);
11. Any component of the study drug or formulation that has caused an allergic reaction, including a known grade ≥3 allergic reaction to other monoclonal antibody-based drugs;
12. Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy and other anti-tumor therapy ≤ 4 weeks before the first dose, except palliative radiotherapy to the bone for pain relief; received nitrosourea or mitomycin C ≤ 6 weeks before the first dose; received fluorouracil and small molecule targeted drugs ≤ 2 weeks or ≤ 5 half-lives of the drug before the first dose; received Chinese medicine with anti-tumor indications ≤ 2 weeks before the first dose;
13. Received another unlisted clinical study drug or treatment ≤ 4 weeks prior to the first dose;
14. Major surgery ≤4 weeks prior to first dose or expected during this study;
15. Immunosuppressive drugs required ≤ 2 weeks prior to first dose or during the study period, excluding: a) intranasal, inhaled, topical glucocorticoids or topical glucocorticoid injections ; b) physiological doses of systemic glucocorticoids (≤ 10 mg/day prednisone or equivalent); c) short-term use of glucocorticoids for prophylaxis or treatment of non-autoimmune allergic diseases;
16. Subjects with known active, or with a history of autoimmune disease with a risk of relapse, or patients at high risk. However, the following patients are allowed to be enrolled: patients with type I diabetes who are stable with a fixed dose of insulin; autoimmune hypothyroidism who require only stable hormone replacement therapy; skin diseases that do not require systemic therapy;
17. Subjects with known history of interstitial lung disease, non-infectious pneumonia, or high suspicion of interstitial lung disease; subjects with previous drug-derived or radiological non-infectious pneumonia who are asymptomatic are allowed to be enrolled;
18. HIV positive, or other acquired or congenital immunodeficiency disease, or history of organ transplantation, or history of stem cell transplantation
19. HBsAg positive, and peripheral blood HBV DNA titer ≥ 2.5×10\^3 copies/ml or ≥ 500 IU/ml; HCV antibody positive, and HCV-RNA above the lower limit of detection of the analytical method;
20. Active or uncontrollable infection requiring intravenous anti-infective therapy ≤ 2 weeks prior to the first dose;
21. Vaccination with live virus ≤ 4 weeks prior to first dose Seasonal influenza vaccine without live virus allowed;
22. Clinically uncontrollable third interstitial fluid that, in the judgment of the investigator, is not suitable for enrollment;
23. Known concomitant severe medical disease, such as NYHA III, IHD, or MI within 3 months prior to first dose, poorly controlled DM (fasting glucose ≥ 10 mmol/L) or poorly controlled hypertension despite drug therapy;
24. Medical or psychiatric history or history of laboratory abnormalities that may interfere with the interpretation of the results;
25. Subjects with alcohol or drug addiction;
26. Subjects deemed unsuitable for study participation by the investigator.

Primary outcomes:
measure: Objective response rate(ORR)
timeFrame: From date of the first dose until the date of first documented progression or date of receiving new antitumor therapy or date of withdraw informed consent or date of death from any cause, whichever came first，assessed up to 24 months
Secondary outcomes:
measure: Disease control rate(DCR)
timeFrame: From date of the first dose until the date of first documented progression or date of receiving new antitumor therapy or date of withdraw informed consent or date of death from any cause, whichever came first，assessed up to 24 months
measure: Duration of response(DOR)
timeFrame: From date of the first dose until the date of first documented progression or date of receiving new antitumor therapy or date of withdraw informed consent or date of death from any cause, whichever came first，assessed up to 24 months
measure: Progression-free survival(PFS)
timeFrame: From date of the first dose until the date of first documented progression or date of receiving new antitumor therapy or date of withdraw informed consent or date of death from any cause, whichever came first，assessed up to 24 months
measure: Overall survival(OS)
timeFrame: From date of the first dose until the date of first documented progression or date of receiving new antitumor therapy or date of withdraw informed consent or date of death from any cause, whichever came first，assessed up to 24 months
measure: Correlation of PD-L1 expression level with efficacy and prognosis
timeFrame: From date of the first dose until the date of first documented progression or date of receiving new antitumor therapy or date of withdraw informed consent or date of death from any cause, whichever came first，assessed up to 24 months
Other outcomes:
measure: Occurrence of Study Treatment Related Adverse Events
timeFrame: From date of the first dose until the date of first documented progression or date of receiving new antitumor therapy or date of withdraw informed consent or date of death from any cause, whichever came first，assessed up to 24 months
measure: Immunogenicity
timeFrame: From date of the first dose until the date of first documented progression or date of receiving new antitumor therapy or date of withdraw informed consent or date of death from any cause, whichever came first，assessed up to 24 months
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
Study officials:
affiliation: Shanghai East Hospital
name: Ye Guo, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: