Head and Neck Squamous Cell Cancer
Conditions
Brief summary
This study is a Phase Ib/II, open-label, multicenter clinical trial. Here, the study phase Ib is mainly to evaluate safety of combination regimen of Toripalimab and Cetuximab in treatment of relapsed or metastatic HNSCC failing first-line platinum-based therapy and determine the recommended Phase II dose (RP2D); the study phase II is divided into two cohorts. Cohort A used to evaluate the efficacy and safety of the combination of regimen for relapsed or metastatic HNSCC failing first-line platinum-based regimen containing chemotherapy;cohort B used to evaluate the efficacy and safety of the combination regimen for PD-L1-positive HNSCC that have not received prior systemic therapy for relapsed or metastatic disease.
Detailed description
This study is a Phase Ib/II, open-label, multicenter clinical trial. Here, the study phase Ib is mainly to evaluate safety of combination regimen of Toripalimab and Cetuximab in treatment of relapsed or metastatic HNSCC failing first-line platinum-based therapy and determine the recommended Phase II dose (RP2D); the study phase II is divided into two cohorts. Cohort A used to evaluate the efficacy and safety of the combination of regimen for relapsed or metastatic HNSCC failing first-line platinum-based regimen containing chemotherapy;cohort B used to evaluate the efficacy and safety of the combination regimen for PD-L1-positive HNSCC that have not received prior systemic therapy for relapsed or metastatic disease. The study consists of the screening period, treatment period, and follow-up period. The screening period is not more than 28 d; after completion of the examinations and assessment in the screening period, eligible subjects enter the investigational therapy period. The subjects will receive the investigational medical product in accordance with the Protocol until radiologically documented progressive disease as judged by the investigator in accordance with RECIST 1.1 criteria, intolerable toxicity, voluntary termination of the treatment or voluntary withdrawal of the informed consent by the subject, or termination of the treatment as judged by the investigator, or until 2 years of JS001 treatment duration (whichever occurs first).
Interventions
DRUGToripalimab Injection
240mg once per 3 weeks
First infusion 400mg/m2，Subsequent infusions 250mg/m2。once per week
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
： 1. Patients voluntarily participate in this study after full informed consent and sign a written informed consent form; 2. Age \>=18 to \<=75 years at time of consenting; 3. Relapsed or metastatic head and neck squamous cell cancer confirmed histologically or cytologically, and occurred in mouth, oropharynx, laryngopharynx, throat, or paranasal sinus, already being unsuitable to receive local therapy such as surgery or radiotherapy; 4. Phase Ib and Phase II Cohort A:Previously receiving a first-line platinum-based chemotherapy against relapsed or metastatic disease, and developing progressive disease during or after treatment; or receiving platinum-based chemotherapy as neoadjuvant or adjuvant chemotherapy (or chemoradiotherapy), and developing relapse or metastasis within 6 months after end of treatment. 5.Phase II cohort B: 1. No previous systemic treatment for relapsed or metastatic disease. Relapse or metastasis more than 6 months after the end of treatment if previously treated with systemic therapy as part of local treatment. 2. Qualified tumor tissue samples with positive PD-L1 expression (defined as Combined Positive Score (CPS) ≥ 1) tested by the central laboratory are required. 6\. All acute toxic reactions from prior antitumor therapy, surgical procedures, or radiotherapy, etc., are relieved to Grades 0-1 (in accordance with NCI-CTCAE version 5.0) or to the level specified in the inclusion/
Exclusion criteria
. Hair loss or pigmentation, or other toxicities that would not result in safety risk to subjects and would not influence compliance, as considered by the investigator, Are ruled out. 7\. Previous tumor samples or fresh tumor tissue biopsy samples may be provided. 8 For subjects with oropharyngeal cancer, a prior test report for HPV16 may be provided, or eligible tumor tissue samples are provided to test HPV status. 9\. At least one measurable lesion in accordance with RECIST 1.1 assessment criteria; 10 Patients with life expectancy \>=12 weeks; 11\. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1 point; 12\. Good organ function level: System organ Lab Value Hematology (no blood transfusion or colony-stimulating factor or other drug correction within 14 days prior to the first study dose) Neutrophil count ≥1.5×10\^9/L Platelet count ≥100×10\^9/L Hemoglobin ≥90 g/L Kidney function Serum creatinine \<=1.5 x upper limit of normal (ULN) or Creatinine clearance is calculated with reference to the Cockcroft-Gault formula or the site practices ≥50 mL/min Hepatic function total Bilirubin \<=1.5 x ULN or\<=3 x ULN (patients with known Gilbert's disease) ALT/AST \<=3 x ULN (without liver metastasis) or\<=5 x ULN (in case of liver metastases) Albumin (no infusion of albumin product with 14 days prior to the first dose of the investigational medical product)≥30g/L Coagulation function International normalized ratio (INR) Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) \<=1.5 x ULN 13\. Within 72 h prior to the first dose, for women of childbearing age must confirm that the serum pregnancy test is negative and agree to adopt effective contraceptive measures during use of the investigational medical product and for 5 months after last dose. A female of childbearing potential in this Protocol is defined as a sexually mature female who: 1\) No hysterectomy or bilateral oophorectomy, 2) Spontaneous menopause does not last for 24 consecutive months (amenorrhea after cancer treatment does not rule out fertility) (i.e., menstruation at any time within the previous 24 consecutive months). Male patients with partners of childbearing potential must agree to use effective contraception during the use of the investigational medical product and for 5 months after last dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse event (AE) and serious adverse event (SAE)-Phase1 | Up to 2 years | Incidence and severity of adverse event (AE) and serious adverse event (SAE) judged in accordance with NCI-CTCAE V5.0; and abnormalities in vital signs, ECG and laboratory tests, etc. |
| Objective response rate(ORR)evaluated by RECIST 1.1-Phase2 | Up to 2 years | Evaluate efficacy of the combination therapy in treatment of relapsed or metastatic HNSCC in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), as objective response rate (ORR) evaluated |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate（DCR）and Duration of response（DOR）and progression-free survival (PFS).-Phase2 | Up to 2 years | Evaluate efficacy of the combination therapy in treatment of relapsed or metastatic HNSCC as disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS). |
| Incidence and severity of adverse event (AE) and serious adverse event (SAE) judged in accordance with NCI-CTCAE V5.0 | Up to 2 years | Incidence and severity of adverse event (AE) and serious adverse event (SAE) judged in accordance with NCI-CTCAE V5.0; and abnormalities in vital signs, ECG and laboratory tests, etc. |
| Overall survival（OS） | Up to 2 years | Evaluate efficacy of the combination therapy in treatment of relapsed or metastatic HNSCC as overall survival (OS) and 1-year OS |
| Objective response rate(ORR)evaluated by the investigator-Phase2 | Up to 2 years | Evaluate efficacy of the combination therapy in treatment of relapsed or metastatic HNSCC in accordance with RECIST 1.1, as objective response rate (ORR) evaluated by the investigator. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 dose (RP2D)-Phase1 | Up to 2 years | Recommended Phase 2 dose (RP2D) of the combination therapy. |
Countries
China
Contacts
Primary Contactpeng zhou, Project Manager
Outcome results
None listed