Clinical Trial of SIBP-03 in Patients With Head and Neck Squamous Cell Carcinoma

A Phase II Clinical Study to Evaluate the Efficacy and Safety of SIBP-03 Injection Combined With Cetuximab in Patients With Recurrent/Metastatic Advanced Head and Neck Squamous Cell Carcinoma (Non-nasopharyngeal Carcinoma)

This phase II study will be conducted in two parts at the same time, with a 21-day treatment cycle until disease progression, intolerable toxicity, withdrawal of informed consent, death, initiation of new anti-tumor treatment or loss of follow-up.

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: HER3 Monoclonal antibodies; Drug: Cetuximab injection; Other: Placebo

Detailed Description

The participants in both study parts are the same, both of whom were patients with recurrent/metastatic advanced HNSCC (non nasopharyngeal carcinoma).

Part one is a one-arm, open-ended study. First, 3 subjects were treated with SIBP-03 15mg/kg every 3 weeks (Q3W) combined with cetuximab every week (QW). If 1/3 subjects (1 case) have DLT, 3 more subjects need to continue to observe the safety and tolerance; If DLT occurs in 3 cases or ≥ 2 cases in 6 cases, the sponsor and the researcher will discuss and decide whether to terminate this part of the study or change the dose. 12 subjects were added at most.

Part two is a randomized, double-blind study. Including a trial group and a placebo control group. The qualified subjects in this stage will be randomly assigned according to the ratio of 2: 1, including 38 cases in the experimental group and 19 cases in the control group, with a total of 57 subjects. Randomization was stratified according to ECOG scores (0 and 1) and stages (non-stage IV and stage IV).

• Study Type: Interventional
• Enrollment (Estimated): 69
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dandan Chen, Master; Phone Number: 86-021-62800991; Email: ddchen.sh@sinopharm.com
• Study Contact Backup: Name: Ye Guo, Doctor; Phone Number: 86-13501678472; Email: pattrickguo@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The subjects voluntarily participated in the study and signed the informed consent.
• Male and female aged between 18 and 75 years old, regardless of gender.
• Patients with recurrent/metastatic advanced HNSCC who have been diagnosed by histology or cytology, progressed or intolerant after previous immunotherapy containing anti-PD-1/anti-PD-L1 and platinum, and have no indication of radical local treatment. Subjects should not receive more than 2 lines of treatment in the past.
• During the screening period, subjects must provide tumor tissues and blood samples for biomarker detection. If the subject does not have an archived tumor tissue sample, he or she will undergo a fresh tumor biopsy during the screening period to obtain the corresponding tumor sample. If the subject can't provide archived or fresh tumor tissue samples, but can provide the previous test reports of qualified institutions, including all biomarker indicators specified in this scheme, they can be screened after communicating with the sponsor.
• There must be at least one measurable lesion as the target lesion (according to RECIST v1.1 standard). Tumor lesions located in previous radiotherapy areas or other local regional treatment sites are generally not measurable lesions unless the lesion has definite progression.
• The ECOG physical fitness score is 0-1.
• The laboratory test results meet the requirements.
• The expected survival time is ≥ 3 months.
• In fertile female subjects, the blood pregnancy test must be negative within 7 days before the first medication. Subjects of reproductive age (including male subjects) had no family planning during the trial period and within 6 months after the last administration and voluntarily took effective contraceptive measures.

Exclusion Criteria:

• The primary site of squamous cell carcinoma is nasal cavity, paranasal sinuses, nasopharynx and salivary gland.
• The participant has received any HER3 targeting or EGFR targeting therapy in the past.
• Active central nervous system metastasis and/or meningeal metastasis.
• Previous allergy to human normal immunoglobulin or antibody preparation or other serious infusion reaction; Severe hypersensitivity disease, allergic constitution.
• In the past 5 years, the subjects had suffered from malignant tumors other than those treated in this study (except cured thyroid cancer, skin basal cell carcinoma and cervical carcinoma in situ).
• People infected with active human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B vrius (HBV), syphilis or active tuberculosis, and asymptomatic chronic hepatitis B or hepatitis C carriers may be excluded.
• The subjects have not recovered from the toxicity of previous anti-tumor therapy to grade ≤ 1 or baseline level (except participants with hair loss, neuropathy of grade ≤ 2 or stabilized thyroid function's decline by hormon replacement therapy).
• Subjects are currently participating in and receiving research treatment or have been treated with other research drugs or medical devices within 4 weeks before the first use of research drugs.
• Patients who plan to receive any other anti-tumor treatment during the trial should be excluded.
• Major surgery, radiotherapy (except palliative radiotherapy for targeted bone metastasis), or treatment such as unhealed surgical wound, ulcer or fracture within 4 weeks before the first administration; Received Chinese patent medicines or Chinese herbal medicines with anti-tumor indications within 2 weeks before the first administration; Chemotherapy was received within 3 weeks before the first administration, and anti-tumor treatments such as biotherapy, endocrine therapy, targeted therapy and immunotherapy were received within 4 weeks
• Those who have been vaccinated live within 30 days before the first administration.
• Active infections requiring systemic treatment, such as pneumonia, bacteremia, septicemia, etc.
• A history of pulmonary interstitial disease, pulmonary interstitial fibrosis or drug-induced interstitial pneumonia or other clinically serious lung diseases (CTCAE 5.0 grade III-IV).
• Pulmonary thromboembolism, arterial thrombosis and deep vein thrombosis formation (DVT) occurred within 6 months before screening, except for infusion set-related thrombosis.
• Have a history or evidence of cardiovascular (CV) risk.
• During the screening period, 12-lead electrocardiogram (ECG) measurement was performed in the research center (the average value of QTcF that needs to be measured repeatedly for 3 times), and the QT interval (QTcF) corrected by Fridericia method was > 450 milliseconds (male) or (QTcF) > 470 milliseconds (female); LVEF of cardiac ultrasound was less than 50%.
• Therapeutic surgery was performed within 28 days before the first administration, or major surgery was expected during the study period (except diagnosis, biopsy and drainage).
• People with mental disorders or poor compliance.
• Pregnant or lactating women.
• According to the researcher's judgment, there are accompanying diseases (such as severe hypertension, diabetes, thyroid diseases, etc.) that seriously endanger the patient's safety or affect the patient's completion of the study.
• Suffering from diseases requiring long-term treatment with high doses (defined as 30mg/d hydrocortisone or equivalent doses of other hormonal drugs) of hormones or immunosuppressive drugs.
• After active treatment, uncontrollable pleural and abdominal cavity or other lacunar effusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Experimental group in part one. It will be 10mg/kg or 15mg/kg of SIBP-03. It will determine whether a 15mg/kg dose study is necessary based on actual research results.	Drug: HER3 Monoclonal antibodies; 10mg/kg or 15mg/kg, intravenous infusion (IV), once every three weeks, 21 days as a cycle. The infusion time is 90 min (± 5 min).; Drug: Cetuximab injection; Inject cetuximab every week, intravenous infusion (IV), once every three weeks, 21 days as a cycle. The infusion time was 90 min (± 5 min).
Experimental: Group A; Experimental group in part two. Its dose will be determined by results of study part one, and the tentative dose is 10mg/kg.	Drug: HER3 Monoclonal antibodies; 10mg/kg or 15mg/kg, intravenous infusion (IV), once every three weeks, 21 days as a cycle. The infusion time is 90 min (± 5 min).; Drug: Cetuximab injection; Inject cetuximab every week, intravenous infusion (IV), once every three weeks, 21 days as a cycle. The infusion time was 90 min (± 5 min).
Placebo Comparator: Group B; Placebo of SIBP-03 (SIBP-03 solvent without HER3 antibody), and the dose will be the same with group A.	Drug: Cetuximab injection; Inject cetuximab every week, intravenous infusion (IV), once every three weeks, 21 days as a cycle. The infusion time was 90 min (± 5 min).; Other: Placebo; 10mg/kg (provisional dosage) every three weeks, intravenous infusion (IV), once every three weeks, 21 days as a cycle. The infusion time was 90 min (± 5 min).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of any adverse events (AE)	All subjects after receiving the investigational drug were observed during the trial for any AE that occurred during the clinical study.AE were manifested as symptoms, signs, diseases, or abnormal laboratory tests, but may not necessarily have a causal relationship with the investigational drug.	30 days after the last dose
SAE (Serious Adverse Events)	That is serious adverse events, any serious adverse events that occurred to the subject during the study period.	30 days after the last dose
Cmax (Peak Plasma Concentration)	It shows the highest plasma concentration of a drug that can be achieved after administration.	30 days after the last dose
Tmax(Peak Time)	That is peak time of drug action, it shows the time required to reach the maximum concentration on the subject plasma concentration curve after administration.	30 days after the last dose
T ½(Terminal elimination half-life)	It reflects how quickly the drug is eliminated from the body.	30 days after the last dose
CL(Clearance Rate)	Apparent volume of drug distribution removed from the body per unit time.	30 days after the last dose
Difference of ORR	Differences in ORR between SIBP-03 and placebo evaluated by the Independent Evaluation Committee (IRC) according to RECIST 1.1. Only applicable to part two.	The 1 day the test results reported after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR (Objective Response Rate)	The proportion of subjects whose tumor volume shrinks to a predetermined value and maintains the minimum time limit, and is the sum of complete and partial responses.	The 1 day the test results reported after the last dose
DCR (Disease control rate)	In clinical trials, the percentage of subjects with advanced or metastatic cancer who responded fully to cancer treatment, partially responded, and had stable disease.	The 1 day the test results reported after the last dose
PFS (Progression-free survival)	The time between the onset of randomization and the onset (of any aspect) of tumor progression or death (from any cause).	The 1 day the test results reported after the last dose
ADA (Anti-drug Antibody)	The incidence of anti-drug antibody.	The 1 day the test results reported after the last dose
NAb (Neutralizing Antibody)	The incidence of neutralizing antibody.	The 1 day the test results reported after the last dose

Collaborators and Investigators

• Sponsor: Shanghai Institute Of Biological Products
• Investigators: Principal Investigator: Ye Guo, Doctor, Shanghai Oriental Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 28, 2023
• Primary Completion (Estimated): May 30, 2025
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: December 22, 2023
• First Posted (Estimated): January 8, 2024

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibodies; Antibodies, Monoclonal; Cetuximab
• Other Study ID Numbers: SIBP-03-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No