A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This is a study to determine the clinical benefit (how well the drug works), safety and tolerability of combining CDX-3379 and cetuximab. The study will enroll patients with advanced head and neck squamous cell carcinoma who have previously received cetuximab and progressed.

Detailed Description
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CDX-3379 is a fully human monoclonal antibody that binds to a molecule called human epidermal growth factor receptor 3 (HER3 or ErbB3) found on certain cells and may act to promote anti-tumor effects. Cetuximab is a human monoclonal antibody that blocks EGFR, a protein receptor that regulates cell growth. This study will evaluate the safety, tolerability and efficacy of CDX-3379 in combination with cetuximab in patients with advanced head and neck squamous cell carcinoma who have previously received cetuximab and progressed. Eligible patients that enroll in the study will be given the dose of 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab. Up to 45 patients will be enrolled. All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

Official Title
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A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of CDX-3379 in Combination With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma

Conditions
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Advanced Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: CDX-3379 and cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed head and neck squamous cell carcinoma. Human papilloma virus (HPV) negative tumor. Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate. Prior treatment with cetuximab with tumor progression during or within 6 months after completing treatment. Measurable disease. Life expectancy ≥ 12 weeks. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 6 months following last treatment. Willingness to undergo a tumor biopsy prior to starting treatment (or if biopsy is not feasible, provide archival tissue). Exclusion Criteria: Previous treatment with CDX-3379 or other anti-ErbB3 targeted agents. Nasal, paranasal sinus, or nasopharyngeal carcinoma, aside from WHO Type I and II (keratinizing, non-EBV positive) nasopharyngeal carcinoma which will be allowed. Major surgery within 4 weeks prior to first dose of study treatment. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment. Monoclonal based therapies within 4 weeks (excluding cetuximab) and all other immunotherapy within 2 weeks prior to first dose of study treatment. Other prior malignancy, active within 3 years, except for localized prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, stage 1 differentiated thyroid cancer or ductal carcinoma in situ of the breast. Active, untreated central nervous system metastases. Active autoimmune disease or documented history of autoimmune disease. Significant cardiovascular disease including CHF or poorly controlled hypertension.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDX-3379 and cetuximab<br>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression. | Drug: CDX-3379 and cetuximab<br>* Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The percentage of patients who achieve a complete response or partial response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions. | The proportion of evaluable patients who achieve a best overall response of complete or partial response according to RECIST 1.1 assessed up to 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Response (CBR) | The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks | Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years | 
| Duration of Response (DOR) | The interval from which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) until the first date that progressive disease is objectively documented | First occurrence of a documented objective response to disease progression or death (up to approximately 2 years) | 
| Progression-free Survival (PFS) | The time from start of study drug to time of progression or death, whichever occurs first | From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years) | 
| Overall Survival (OS) | The time from start of study drug to death | The time from start of study drug to death from any cause (up to approximately 2 years) | 
| Incidence of Adverse Events [Safety and Tolerability] | Safety and tolerability of CDX-3379 in combination with cetuximab as determined by incidence and severity of adverse events. Percentage of patients reporting one or more adverse events. | Following at least one dose of study treatment through 30 days after last dose of CDX-3379. | 
| Tumor DNA Biomarkers. | Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy. Objective response rate for subset of patients with FAT1 positive tumor is reported. | Tumor tissue is obtained during screening window via single biopsy procedure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erbitux, Cetuximab, Oral Cancer, Oropharyngeal cancer, Laryngeal cancer, Head and Neck Squamous Cell Carcinoma