Neoadjuvant Toripalimab + Chemotherapy ± Cetuximab in Locally Advanced Head and Neck Squamous Cell Carcinoma (Neo-ICT)

NCT06647563 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: JYKQ-2024-105
• Study Type: interventional
• Target: 355
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a randomized, active-controlled, open-label clinical trial for participants with newly diagnosed Stage III-IVb, resectable, locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). The study consists of two experimental arms and one control arm. Participants in Experimental Arm A will receive two cycles of Toripalimab, albumin-bound paclitaxel, carboplatin, and cetuximab prior to surgery. Participants in Experimental Arm B will receive two cycles of Toripalimab, albumin-bound paclitaxel, and carboplatin before surgical intervention. Following the surgical procedure, individuals in both Experimental Arm A and B will continue to receive 15 cycles of Toripalimab. The Control Arm will undergo the current standard treatment without preoperative drug intervention. Postoperatively, participants will be administered postoperative radiotherapy or chemoradiotherapy based on their recurrence risk. The primary study hypotheses are that the treatments in the Experimental Arms will improve the 2-year event-free survival (EFS) rates compared to the standard control treatment.

Conditions

Squamous Cell Carcinoma of Head and Neck

Keywords

Programmed Cell Death-1 (PD1, PD-1); Head and Neck Squamous Cell Carcinoma; Toripalimab; Albumin-bound paclitaxel; Carboplatin; Cetuximab; Neoadjuvant

Outcome Measures

Primary Outcomes (2)

• ICT vs Control: Two-Year Event-free Survival (EFS) rate

  Two-Year Event-free Survival (EFS) rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Two-Year EFS rate in the ICT arm will be compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population.

  Up to ~72 months

• IC vs Control: Two-Year EFS rate

  Two-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Two-Year EFS rate in the IC arm will be compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population.

  Up to ~72 months

Secondary Outcomes (20)

• ICT vs Control: Overall Survival (OS)

  Up to ~96 months

• IC vs Control: OS

  Up to ~96 months

• ICT vs IC: Major Pathological Response (MPR)

  Up to ~40 months

• ICT vs IC: Pathological Complete Response (PCR)

  Up to ~40 months

• ICT vs IC: Objective Response Rate (ORR)

  Up to ~40 months

Study Arms (3)

Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)

EXPERIMENTAL

Participants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m\^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1, and Cetuximab 400mg/m\^2 on Day 1, followed by Cetuximab 250mg/m\^2 on Day 1 of each subsequent week. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m\^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles.

Biological: Toripalimab; Biological: Cetuximab; Drug: Albumin-Bound Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Radiation: Radiotherapy 60 Gray/day; Radiation: Radiotherapy 66 Gray/day; Radiation: Radiotherapy 70 Gray/day

Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)

EXPERIMENTAL

Participants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m\^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m\^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles.

Biological: Toripalimab; Drug: Albumin-Bound Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Radiation: Radiotherapy 60 Gray/day; Radiation: Radiotherapy 66 Gray/day; Radiation: Radiotherapy 70 Gray/day

No Neoadjuvant + SOC (Control)

ACTIVE COMPARATOR

Participants will receive the standard of care (SOC) with no neoadjuvant prior to surgery. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m\^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy.

Drug: Cisplatin; Radiation: Radiotherapy 60 Gray/day; Radiation: Radiotherapy 66 Gray/day; Radiation: Radiotherapy 70 Gray/day

Interventions

Toripalimab BIOLOGICAL

Specified dose on specified days

Also known as: PD-1 antibody

Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT); Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)

Cetuximab BIOLOGICAL

Specified dose on specified days

Also known as: EGFR antibody

Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT)

Albumin-Bound Paclitaxel DRUG

Specified dose on specified days

Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT); Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)

Carboplatin DRUG

Specified dose on specified days

Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT); Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)

Cisplatin DRUG

Specified dose on specified days

No Neoadjuvant + SOC (Control); Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT); Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)

Radiotherapy 60 Gray/day RADIATION

Low risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy.

No Neoadjuvant + SOC (Control); Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT); Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)

Radiotherapy 66 Gray/day RADIATION

High risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy.

No Neoadjuvant + SOC (Control); Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT); Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)

Radiotherapy 70 Gray/day RADIATION

Participants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy.

No Neoadjuvant + SOC (Control); Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT); Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed squamous cell carcinoma of the head and neck (excluding nasopharyngeal cancer);
• Male or female, aged 18-75 years;
• Clinical stage III-IVb (AJCC 8th edition TNM stage) and operable patients; if oropharyngeal squamous cell carcinoma (P16-), the stage is III-IVb; if oropharyngeal squamous cell carcinoma (P16+), the stage is III;
• No prior antitumor therapy including radiotherapy, chemotherapy, immunotherapy or biological therapy for the current tumor;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
• Life expectancy ≥ 6 months;
• No obvious contraindications to immunotherapy, radiochemotherapy, or surgical treatment;
• Willing to accept surgical treatment;
• The level of main organ function meets the following criteria:
• Routine blood tests: WBC ≥ 4.0 × 10\^9/L, ANC ≥ 1.5 × 10\^9/L, PLT ≥ 100 × 10\^9/L, Hb ≥ 90 g/L (no blood transfusion or blood products within 14 days, no correction with G-CSF and other hematopoietic growth factors);
• Biochemical assessments: serum albumin ≥ 3.0 g/dL (30 g/L), TBIL ≤ 1.5 × ULN, ALT, AST ≤ 2.5 × ULN, BUN and CRE ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula);
• Adequate coagulation function: defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN; If the subject is receiving anticoagulant therapy, PT should be within the proposed therapeutic range of the anticoagulant;
• Women of childbearing potential must have a negative pregnancy test result (serum or urine), conducted within seven days prior to enrollment and agree to use effective contraception during the study period and for six months post last dose of anti-PD-1 antibody administration. Male subjects with female partners who are capable of conception must also utilize effective contraception throughout this study duration and for six months after their final dose anti-PD-1 antibody;
• Willingness to participate in this study by signing an informed consent form, while exhibiting strong compliance and readiness to cooperate with follow-up procedures.

You may not qualify if:

• Previous treatment with anti-PD-1/PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, anti-CTLA-4 antibody, or other drugs/antibodies targeting T cell co-stimulation or checkpoint pathway;
• Active autoimmune disease. Subjects in stable condition who do not require systemic immunosuppressive therapy are permitted; examples include type I diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin conditions that do not necessitate systemic treatment (e.g., vitiligo, psoriasis, alopecia).
• Patients with congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10\^4 copies/ml) or hepatitis C (positive antibody for HCV, and HCV-RNA above the lower limit of detection of the analytical procedure);
• Known allergy to the study drug or any of its excipients; or serious allergic reaction to other monoclonal antibodies.
• The occurrence of any of the following conditions within 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, NYHA class II or higher cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure.
• Vaccination with live vaccines within 4 weeks prior to the first dose of the study drug. Inactivated virus vaccine can be administered for seasonal flu, but not attenuated live influenza vaccines administered intranasally.
• Known history of allogeneic organ transplant or allogeneic stem cell transplant.
• The history of drug addiction and the abuse of psychoactive substances.
• Pregnant or breastfeeding women.
• Any other malignant neoplasm diagnosed within 5 years prior to study entry, except for carcinoma that is amenable to local treatment and has been cured, such as basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, carcinoma in situ of breast ductal, and papillary thyroid cancer.
• Patients with other significant physical or mental health conditions, or laboratory test abnormalities that may elevate the risk of participation in the study or compromise the integrity of the study results, as determined by the investigators, are deemed unsuitable for participation in this study.

Sponsors & Collaborators

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: lead

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

toripalimab; spartalizumab; Cetuximab; Albumin-Bound Paclitaxel; Carboplatin; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yue He, M.D.

  Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng Liu, M.D.

CONTACT

18917797783; nuanliu@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: October 13, 2024
• First Posted: October 18, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2030
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share