Induction IBI110 and Sintilimab with Chemotherapy in LA HNSCC

NCT06494943 | Recruiting Phase 1 DMC

• 1 other identifier: Insight 3.0
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the efficacy and safety of combining sintilimab and the TP regimen with/without IBI110 for neoadjuvant chemotherapy in resectable locally advanced head and neck squamous cell carcinoma (HNSCC).

Conditions

Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

Immune checkpoint inhibitor; Neoadjuvant chemotherapy; Induction chemotherapy; PD-1 inhibitor; LAG-3 inhibitor

Outcome Measures

Primary Outcomes (2)

• Major pathological response

  The major pathological response rate (MPR rate), defined as the presence of residual tumor components ≤10% in tumor bed of the primary tumor site and cervical lymph node.

  Up to 3 months, post-surgery

• Adverse Events related to treatment

  Adverse Events related to treatment of sintilimab, IBI110, paclitaxel and cisplatin, per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

  Up to 4 months

Secondary Outcomes (5)

• Pathologic complete response rate

  Up to 3 months, post-surgery

• Objective response rate

  Up to 2 months, prior to surgery

• Progression-free survival rate

  Up to 2 years

• Overall survival rate

  Up to 2 years

• Quality of life asessment

  Up to 2 months, prior to surgery

Other Outcomes (1)

• Tumor Mutation Burden

  Up to 2 months, prior to surgery

Study Arms (2)

Cohort B: IBI110 and sintilimab and TP regimen

EXPERIMENTAL

The first phase is the dose-escalation stage, where fixed doses of IBI110 and sintilimab will be administered, and the doses of paclitaxel and cisplatin will be escalated to determine the Recommended Dose for expansion stage. This phase is divided into three dose groups: paclitaxel 135 mg/m² on day 2 and cisplatin 20 mg/m² on days 2-4; paclitaxel 150 mg/m² on day 2 and cisplatin 20 mg/m² on days 2-4; paclitaxel 175 mg/m² on day 2 and cisplatin 25 mg/m² on days 2-4. The accelerated dose-escalation method will be used. The second phase is the fixed-dose expansion stage. They will receive the recommended doses of paclitaxel and cisplatin, combined with IBI110 200 mg on day 1 every 3 weeks administered intravenously, and sintilimab 200 mg on day 1 every 3 weeks administered intravenously. All subjects will undergo radical surgery after neoadjuvant therapy. Adjuvant radiotherapy (chemoradiotherapy) will be administered postoperatively based on pathological factors as appropriate.

Drug: Sintilimab; Drug: IBI110; Drug: Paclitaxel; Drug: Cis Platinum; Procedure: Surgery; Radiation: Adjuvant radiation

Cohort A: sintilimab and TP regimen

EXPERIMENTAL

The enrolled patients will receive paclitaxel 175 mg/m² on day 2 and cisplatin 25 mg/m² on days 2-4, combined with sintilimab 200 mg on day 1 every 3 weeks administered intravenously, for a total of two cycles. All subjects will undergo radical surgery after neoadjuvant therapy. Adjuvant radiotherapy (chemoradiotherapy) will be administered postoperatively based on pathological factors as appropriate.

Interventions

Sintilimab DRUG

PD-1 inhibitor

Cohort B: IBI110 and sintilimab and TP regimen

IBI110 DRUG

LAG-3 inhibitor

Cohort B: IBI110 and sintilimab and TP regimen

Paclitaxel DRUG

Chemotherapy

Cohort B: IBI110 and sintilimab and TP regimen

Cis Platinum DRUG

Chemotherapy

Cohort B: IBI110 and sintilimab and TP regimen

Surgery PROCEDURE

Definitive surgery

Cohort B: IBI110 and sintilimab and TP regimen

Adjuvant radiation RADIATION

Adjuvant radiotherapy or chemoradiotherapy based on post-operative pathologic findings.

Cohort B: IBI110 and sintilimab and TP regimen

Eligibility Criteria

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

You may qualify if:

• Signed informed consent and willing to complete the study as per the protocol;
• Age ≥ 18 years and ≤ 75 years;
• Histologically confirmed head and neck squamous cell carcinoma, including primary sites in the oropharynx, oral cavity, larynx, and hypopharynx;
• Resectable locally advanced head and neck squamous cell carcinoma (AJCC 8th edition: Stage III-IVB);
• At least one measurable lesion before treatment, meeting the RECIST 1.1 criteria for "measurable disease";
• Expected survival \> 3 months;
• ECOG performance status 0-1;
• Adequate organ function meeting the following criteria:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L;
• Platelet count ≥ 100 × 10\^9/L;
• Hemoglobin ≥ 9 g/dL;
• Serum albumin ≥ 2.8 g/dL;
• Total bilirubin ≤ 1.5 × ULN, ALT, AST, and/or ALP ≤ 3 × ULN;
• Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 60 mL/min (Cockcroft-Gault, see Appendix III);
• Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN (Patients on stable doses of anticoagulants such as low-molecular-weight heparin or warfarin with INR within the therapeutic range may be screened);

You may not qualify if:

• Participants will be excluded from the study if they meet any of the following criteria:
• History of or concurrent other malignancies (excluding those that have been cured with a cancer-free survival period of more than 5 years, such as basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma);
• Receipt of any of the following treatments:
• Any investigational drug within 4 weeks prior to the first use of the study drug;
• Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study;
• Systemic treatment with corticosteroids (daily dose \>10 mg prednisone equivalent) or other immunosuppressive drugs within 2 weeks before the first use of the study drug, except for corticosteroids used for local inflammation and prevention of allergies, nausea, and vomiting. Special cases need to be discussed with the investigator. Inhaled or topical steroids and adrenal corticosteroid replacement therapy with doses \>10 mg/day prednisone equivalent are allowed in the absence of active autoimmune disease;
• Anti-tumor vaccination or live vaccination within 4 weeks prior to the first administration of the study drug (for COVID-19 vaccination, the interval between vaccination and treatment should be more than 2 weeks);
• Major surgery or severe trauma within 4 weeks prior to the first use of the study drug;
• Uncontrolled cardiac clinical symptoms or diseases, such as:
• Heart failure of NYHA class II or higher;
• Unstable angina;
• Myocardial infarction within 1 year;
• Clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
• Severe infections (CTCAE \> Grade 2) within 4 weeks before the first use of the study drug, such as severe pneumonia requiring hospitalization, bacteremia, or complications of infections. Baseline chest imaging indicating active pulmonary inflammation, symptoms and signs of infection within 4 weeks prior to the first use of the study drug, or requiring oral or intravenous antibiotics;
• Active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); except for autoimmune-mediated hypothyroidism treated with a stable dose of thyroid replacement hormone, type 1 diabetes with a stable dose of insulin, vitiligo, or childhood asthma/allergies that have resolved without intervention in adulthood;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (3)

• Ou X, Zhai R, Wei W, Chen J, Ou D, Liao T, Xu T, Zhu Y, Wang Y, Huang S, Shi R, Wu B, Chen T, Li Y, Yang Z, Zhou C, Liu Y, Jiang Z, Zeng M, Liu X, Ji D, Ying H, Zhang Z, Hu C, Lu X, Ji Q, He X, Wang Y. Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial. Clin Cancer Res. 2024 Jan 17;30(2):344-355. doi: 10.1158/1078-0432.CCR-23-2398.

  PMID: 37955629 BACKGROUND

• Long L, Zhang X, Chen F, Pan Q, Phiphatwatchara P, Zeng Y, Chen H. The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Genes Cancer. 2018 May;9(5-6):176-189. doi: 10.18632/genesandcancer.180.

  PMID: 30603054 BACKGROUND

• Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutierrez E, Rutkowski P, Gogas HJ, Lao CD, De Menezes JJ, Dalle S, Arance A, Grob JJ, Srivastava S, Abaskharoun M, Hamilton M, Keidel S, Simonsen KL, Sobiesk AM, Li B, Hodi FS, Long GV; RELATIVITY-047 Investigators. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022 Jan 6;386(1):24-34. doi: 10.1056/NEJMoa2109970.

  PMID: 34986285 BACKGROUND

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

sintilimab; Paclitaxel; Cisplatin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, M.D.

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: July 10, 2024
• Study Start: June 26, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 25, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)