A Phase II Study of Neoadjuvant Immunotherapy in Combination With Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT06444009 | Recruiting Phase 2 DMC

• 1 other identifier: AK112-IIT-C-W-0001
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

A Randomized, Phase II Study of ivonescimab or cadonilimab or penpulimab in Combination With Cisplatin and Nab-paclitaxel in Patients With locally advanced head and neck squamous cell carcinoma (HNSCC) eligible for resection. This proposed study will evaluate the efficacy and safety of preoperative administration of ivonescimab or cadonilimab or penpulimab combined with chemotherapy in HNSCC who are eligible for resection.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

Locally advanced head and neck squamous cell carcinoma; Neoadjuvant therapy; Immunotherapy; AK112

Outcome Measures

Primary Outcomes (1)

• pCR

  Pathological complete response rate

  After surgery (approximately 9-10 weeks after start of study treatment)

Secondary Outcomes (1)

• MPR

  After surgery (approximately 9-10 weeks after start of study treatment)

Other Outcomes (3)

• ORR

  9-10 weeks

• EFS

  1 years

• OS

  2 years

Study Arms (3)

Ivonescimab in combination with Nab-paclitaxel + Cisplatin

EXPERIMENTAL

Neoadjuvant: Patients receive ivonescimab in combination with nab-paclitaxel + cisplatin for 3 cycles before surgery. Surgery: Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection. Adjuvant: pCR: Patients receive adjuvant ivonescimab for 16 cycles. no pCR: Low/ Medium Risk: Patients will be treated with intensity modulation radiation therapy (IMRT) alone. Once radiotherapy is complete these patients will receive adjuvant ivonescimab for 16 cycles High Risk: All patients will be treated with IMRT concurrent with cisplatin or other standard of care chemoradiotherapy regimen. Once chemoradiotherapy is complete these patients will receive adjuvant ivonescimab for 16 cycles.

Drug: Ivonescimab combined with TP

Cadonilimab in combination with Nab-paclitaxel + Cisplatin

EXPERIMENTAL

Neoadjuvant: Patients receive cadonilimab in combination with nab-paclitaxel + cisplatin for 3 cycles before surgery. Surgery: Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection. Adjuvant: pCR: Patients receive adjuvant cadonilimab for 16 cycles. no pCR: Low/ Medium Risk: Patients will be treated with intensity modulation radiation therapy (IMRT) alone. Once radiotherapy is complete these patients will receive adjuvant cadonilimab for 16 cycles High Risk: All patients will be treated with IMRT concurrent with cisplatin or other standard of care chemoradiotherapy regimen. Once chemoradiotherapy is complete these patients will receive adjuvant cadonilimab for 16 cycles.

Drug: Cadonilimab combined with TP

Penpulimab in combination with Nab-paclitaxel + Cisplatin

EXPERIMENTAL

Neoadjuvant: Patients receive penpulimab in combination with nab-paclitaxel + cisplatin for 3 cycles before surgery. Surgery: Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection. Adjuvant: pCR: Patients receive adjuvant penpulimab for 16 cycles. no pCR: Low/ Medium Risk: Patients will be treated with intensity modulation radiation therapy (IMRT) alone. Once radiotherapy is complete these patients will receive adjuvant penpulimab for 16 cycles High Risk: All patients will be treated with IMRT concurrent with cisplatin or other standard of care chemoradiotherapy regimen. Once chemoradiotherapy is complete these patients will receive adjuvant penpulimab for 16 cycles.

Drug: Penpulimab combined with TP

Interventions

Ivonescimab combined with TP DRUG

Both interventions all drugs intravenous infusion, D1, once every 3 weeks, a total of 3 cycles.

Also known as: ITP

Ivonescimab in combination with Nab-paclitaxel + Cisplatin

Cadonilimab combined with TP DRUG

Both interventions all drugs intravenous infusion, D1, once every 3 weeks, a total of 3 cycles.

Also known as: CTP

Cadonilimab in combination with Nab-paclitaxel + Cisplatin

Penpulimab combined with TP DRUG

Both interventions all drugs intravenous infusion, D1, once every 3 weeks, a total of 3 cycles.

Also known as: PTP

Penpulimab in combination with Nab-paclitaxel + Cisplatin

Eligibility Criteria

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

You may qualify if:

• Males and females； Age：18 to 75 years.
• Histologically or cytologically confirmed head and neck squamous cell carcinoma (HNSCC).
• Patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior treatment for the cancer.
• Intention to undergo curative treatment.
• Patients with normal organ function and suitable for immunotherapy combined with chemotherapy and surgery:
• Adequate hematologic function (total white blood cell count ≥ 3.0×10\^9/L, absolute lymphocyte count ≥ 0.8×10\^9/L, absolute neutrophil count ≥ 1.5×10\^9/L, platelets ≥ 100×10\^9/L, hemoglobin ≥ 90g/L); Adequate hepatic function (bilirubin level ≤ 2 times the upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN); Adequate renal function (serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula), urine protein \<2+ on dipstick or \<1g in a 24-hour urine collection); Good cardiac function, i.e., normal or clinically insignificant abnormalities on electrocardiogram (ECG), echocardiogram showing a left ventricular ejection fraction (LVEF) ≥50%; Adequate coagulation function: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times ULN; participants on anticoagulation treatment are eligible if the PT is within the therapeutic range of the anticoagulant;
• Blood pressure well controlled (defined as systolic blood pressure ≤ 150 mmHg and diastolic blood pressure ≤ 90 mmHg) with or without antihypertensive medication, and no change in antihypertensive treatment within 1 week before the first dose of study medication.
• Patients with HBV infection capable of having detectable HBV DNA levels (≥10IU/mL or above the limit of quantitation) (manifested as positive for hepatitis B surface antigen (HbsAg) and/or hepatitis B core antibody (anti-HBc)) must receive antiviral therapy according to clinical practice at the site before randomization to ensure adequate viral suppression. Patients must maintain antiviral therapy during the study and for 6 months after the last dose of study treatment. Patients who are anti-HBc positive but do not have detectable HBV DNA (\<10IU/mL or below the limit of quantitation) are not required to receive antiviral therapy unless their HBV DNA levels exceed 10IU/mL or the limit of quantitation during treatment.
• Women of childbearing potential (15-49 years old) must have a negative pregnancy test within 7 days before starting treatment; patients of childbearing potential must agree to use effective contraception to ensure they do not become pregnant during the study period and for 3 months after stopping treatment.
• Participants voluntarily join the study, sign an informed consent form, have good compliance, and cooperate with follow-up.

You may not qualify if:

• Patients who have received any form of anti-tumor treatment previously.
• Patients with allergic constitution and congenital immune deficiencies.
• Patients who have undergone organ transplantation.
• Patients with a history of severe bleeding tendencies or coagulation dysfunction; those who have had clinically significant bleeding symptoms within 1 month prior to the study treatment, including but not limited to gastrointestinal bleeding, hemoptysis; those who have received prolonged anticoagulation treatment within 10 days prior to the study treatment.
• Patients who have experienced arteriovenous thrombotic events within 6 months before the study treatment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
• Patients with active infections, including tuberculosis or human immunodeficiency virus (HIV 1/2 antibody positive).
• Patients with uncontrollable complications, including but not limited to: persistent or active infections receiving study treatment (except HBV or HCV), symptomatic congestive heart failure, uncontrolled diabetes, uncontrolled hypertension, unstable angina, uncontrolled arrhythmias, active interstitial lung disease, severe chronic gastrointestinal disease with diarrhea, or any psychiatric/social situations that might limit compliance with study requirements, significantly increase the risk of adverse events (AE), or impair the ability of the patient to give written informed consent.
• Pregnant or breastfeeding women.
• Patients who do not agree to use effective contraception during the treatment period and for 3 months thereafter.
• Patients participating in other clinical studies simultaneously.
• Patients who are critically ill and unable to complete the investigation.
• Patients with a history of other primary malignant tumors, except for the following: Malignant tumors treated with curative intent and no known active disease for ≥5 years prior to study treatment and with a low risk of relapse; adequately treated non-melanoma skin cancer or in-situ melanoma without evidence of disease; adequately treated carcinoma in situ without evidence of disease.
• Patients with a history of psychiatric illness (e.g., schizophrenia, mania, anxiety disorder, depression, phobia) or diagnosed with a psychiatric disease at the time of enrollment or their spouses.
• Patients or their spouses with communication barriers due to confusion, aphasia, intellectual disability, or other reasons that prevent normal responses.
• Patients with other malignant neoplastic diseases.

Sponsors & Collaborators

• Lei Liu: lead

Study Sites (1)

West China Hospital

Chengdu, Sichuan, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Inosine Triphosphate; Cytidine Triphosphate

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)

Inosine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Cytosine Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Lei Liu, M.D.

CONTACT

Liu; liuleihx@gmail.com

Yuanyuan Zeng, M.D.

CONTACT

+86-028-85422114; zengyuanyuanpower@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Model Details: A Randomized, Controlled, Phase II Study

Study Record Dates

• First Submitted: May 30, 2024
• First Posted: June 5, 2024
• Study Start: July 1, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 2, 2024

Record last verified: 2024-11

Locations

CN (1)