Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Cetuximab

Immunoglobulins

Immunologic Factors

Antineoplastic Agents, Immunological

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.

Experimental group in part two. Its dose will be determined by results of study part one, and the tentative dose is 10mg/kg.

Placebo of SIBP-03 (SIBP-03 solvent without HER3 antibody), and the dose will be the same with group A.

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).

HER3 Monoclonal antibodies

Inject cetuximab every week, intravenous infusion (IV), once every three weeks, 21 days as a cycle. The infusion time was 90 min (± 5 min).

Cetuximab injection

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).

Placebo

Dandan Chen, Master

Ye Guo, Doctor

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.

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).

Part one is a one-arm, open-ended study and part two is a randomized, double-blind study.

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)

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.

That is serious adverse events, any serious adverse events that occurred to the subject during the study period.

It shows the highest plasma concentration of a drug that can be achieved after administration.

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.

It reflects how quickly the drug is eliminated from the body.

Apparent volume of drug distribution removed from the body per unit time.

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 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.

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 time between the onset of randomization and the onset (of any aspect) of tumor progression or death (from any cause).

Shanghai Institute Of Biological Products

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Recombinant anti-EGFR human mouse chimeric monoclonal antibody injection 250mg/m2 single administration

Cetuximab,Erbitux 250mg/m2 single administration

Recombinant anti-EGFR human mouse chimeric monoclonal antibody injection

anti-EGFR monoclonal antibody

Li Jin, doctor

Colorectal cancer (CRC) is one of the most common human malignant tumors. The incidence and mortality of colorectal cancer in our country are on the rise. Surgery-based, combined with chemotherapy, radiotherapy comprehensive treatment, is the main treatment of colorectal cancer. Surgical resection has been recognized as the primary treatment of colorectal cancer. However, due to the majority of patients already advanced at the time of diagnosis, some difficulties are brought to radical surgery. Therefore, the importance of chemotherapy for colorectal cancer gradually been clinically recognized, But rarely survive more than 18 months." In addition to chemotherapy, there is now a more ideal model of cancer treatment- molecular targeted therapies, including monoclonal antibody drugs such as cetuximab, as well as small molecule tyrosine kinases Inhibitors gefitinib and so on. Molecular targeted drugs make use of the difference in molecular biology between tumor cells and normal cells. Targeting drugs to tumor cells and inhibiting the growth and proliferation of the cells can achieve the therapeutic effect, which has the advantages of high specificity and low adverse reaction. The bio-targeted drug cetuximab is the first drug approved to marketed as an epidermal growth factor receptor (EGFR)-targeting immunoglobulin 1（IgG1）monoclonal antibody. Cetuximab, either monotherapy or combined radiotherapy and chemotherapy, can exert excellent anti-tumor activity in EGFR-positive malignant tumors and can significantly enhance the efficacy of radiotherapy and chemotherapy.

Reference to cetuximab injection, guilin sanjin Co., Ltd. and dragonboat Co., Ltd. jointly developed a recombinant anti-EGFR human mouse chimeric monoclonal antibody (R \& D code: CDP1).The primary structure of CDP1 is exactly the same with cetuximab, the higher structure and Physical and chemical properties and cetuximab are highly similar. Pharmacodynamic activity in vivo and in vitro, pharmacokinetic characteristics and toxicological reactions are also similar to cetuximab. CDP1 selected with cetuximab consistent formulations, prescriptions, specifications.

CDP1 was approved by China Food and Drug Administration (No. 2016L06884) in August 2016 for clinical studies. According to the contents of the document and guidelines for biological analogs, the clinical pharmacokinetic and clinical effectiveness comparison tests of CDP1 and the safety and immunogenicity assessment are planned.

OBJECTIVES:

Primary:

To compare the pharmacokinetic characteristics of a single dose between CDP1 and the original drug Erbitux In patients with advanced metastatic colorectal cancer.

Secondary :

1. To compare the safety and immunogenic characteristics of the single dose between CDP1 and the original drug Erbitux in patients with advanced metastatic colorectal cancer.
2. To evaluate the pharmacokinetics and safety of CDP1 multiple administrations."

OUTLINE

The study can be divided into 3 parts:

Part 1: Single-dose Phase:

single center, parallel, randomized, single-blind trial. The original drug Erbitux as a control, CDP1 and Erbitux single-dose pharmacokinetics of the initial comparison, and at the same time safety and immunogen preliminary comparison. CDP1 group received a single administration of CDP1 250mg/m2, Erbitux group received Erbitux 250mg/m2 single administration. Two groups of subjects after a single administration into the 4-week observation period, safety observations, pharmacokinetic blood samples and immunogenic blood samples were collected. The tumor was evaluated at the end of the 4 week observation period.If the subjects did not develop the disease, or did not appear the intolerant toxicity during the observation period, they entered the period of multiple drug delivery.

Part 2: Multi-dose Phase:

Single center, single arm, open trial, evaluation of pharmacokinetics and safety with multiple doses of CDP1. Multiple administrations of two groups of subjects were followed by continuous administration of CDP1. Dosing regimen is the first administration of 400mg/m2, followed by 250mg/m2, once a week for 6 weeks.

Part 3: Follow-up Phase:

CDP1, IV, once a week, 250mg/m2, until the patient's death or the withdrawal decision of the patient and/or investigator.

A Preliminary Clinical Study on the Pharmacokinetics and Safety of CDP1 in Patients With Advanced CRC or HNSCC

A Preliminary Clinical Study on the Pharmacokinetics and Safety of Recombinant Anti-EGFR Human Mouse Chimeric Monoclonal Antibody Injection (CDP1) in Patients With Advanced Colorectal Cancer or Head and Neck Squamous Cell Carcinoma

Single-dose Phase: Pharmacokinetic parameters: AUC(0-t) for CDP1

Single-dose Phase: Pharmacokinetic parameters: AUC(0-00) for CDP1

Single-dose Phase: Pharmacokinetic parameters Cmax for CDP1

Single-dose Phase: Pharmacokinetic parameters MRT for CDP1

Single-dose Phase: Pharmacokinetic parameters T1/2 for CDP1

Single-dose Phase: Pharmacokinetic parameters CL for CDP1

ECOG performance status measured to assess subject's performance status on a scale of 0 to 4, where 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory (\>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=Capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4=Completely disabled, cannot carry on any self-care, totally confined to bed/chair. ECOG performance status was reported in terms of number of subjects with Baseline value vs. worst post-baseline value (i.e. highest score) combination.

ECOG performance status measured to assess subject's performance status on a scale of 0 to 4, where 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=Ambulatory (\>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=Capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4=Completely disabled, cannot carry on any self-care, totally confined to bed/chair. ECOG performance status was reported in terms of number of subjects with Baseline value vs. best post-baseline value (i.e. lowest score) combination.

Immunogenicity indicators: Anti-drug antibodies (ADA) .

Immunogenicity indicators: neutralizing antibodies (Titers and Nab analyzes will be performed when ADA screening is positive).

Shanghai East Hospital

Dragonboat Biopharmaceutical Company Limited

Irinotecan

Avelumab

Topoisomerase I Inhibitors

Enzyme Inhibitors

Avelumab : administrated at a fixed dose of 10 mg/kg once every 2- week. Cetuximab: administered at 400 mg/m2 loading dose week 1, 250 mg/m2 from week 2 followed by 500 mg/m2 from week 3.

Irinotecan: administrated every 2 weeks (180 mg/m2).

Avelumab will be administered at a fixed dose of 10 mg/kg once every 2- week

Cetuximab will be administered at 400 mg/m2 loading dose week 1, 250 mg/m2 from week 2 followed by 500 mg/m2 from week 3 and irinotecan administered every 2 weeks (180 mg/m2).

Cetuximab Injection

Irinotecan will be administered every 2 weeks (180 mg/m2)

Marc Van Den Eynde, MD, PhD

Marie-Laure Castella, Study coordinator

Javier Carrasco, MD, PhD

Cancer immunotherapy with immunostimulatory antibodies targeting the CTLA-4 or PD-1/PD-L1 pathways has demonstrated its efficacy in variable proportions of cancer. For metastatic colorectal cancer (mCRC) it appeared that only the small subgroup of patients with MSI-H tumors (microsatellite instability-high phenotype) had a clinically meaningful response to the anti-PD-1- L1 antibodies. In the majority group of non-MSI-H CRC (90-95% of patients), current research expect that additional means would be able to render the tumor "immunogenic" (like MSI-H CRC) and increase the intratumoral immune infiltrate which is the prerequisite to observe a benefit from PD1-PD-L1 inhibitors. Combinations of immune checkpoint inhibitors and procedures that increase intratumoral immune responses, such as targeted therapy, are actively explored.

Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer

Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer - A Proof of Concept, Open Label Non-randomized Phase IIa Study. The AVETUXIRI Trial

The overall tumor response rate (ORR) defined as the proportion of all included patient with a confirmed best overall tumor response of PR or CR according to irRECIST 1.1 occuring until 19 weeks after study treatment start.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Trial of SIBP-03 in Patients With Head and Neck Squamous Cell Carcinoma	NCT06194656	Head and Neck S...	HER3 Monoclonal... Cetuximab injec... Placebo	18 Years - 75 Years	Shanghai Institute Of Biological Products
A Preliminary Clinical Study on the Pharmacokinetics and Safety of CDP1 in Patients With Advanced CRC or HNSCC	NCT03491709	Colorectal Canc...	anti-EGFR monoc... Cetuximab injec...	18 Years - 75 Years	Dragonboat Biopharmaceutical Company Limited
Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer	NCT03608046	Colorectal Neop...	Avelumab Cetuximab Injec... Irinotecan	18 Years - 100 Years	Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Spots Global Cancer Trial Database for cetuximab injection