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

Phase 2

Terminated

• Conditions: Advanced Head and Neck Squamous Cell Carcinoma
• Interventions: Drug: CDX-3379 and cetuximab

• Registration Number: NCT03254927
• Lead Sponsor: Celldex Therapeutics

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-08-17
• Study First Submitted QC: 2017-08-17
• Study First Posted: 2017-08-21
• Study Start: 2018-03-27
• Primary Completion: 2020-09-16
• Study Completion: 2020-12-16
• Results First Submitted: 2021-10-06
• Status Verified: 2023-03
• Results First Submitted QC: 2023-03-07
• Last Update Submitted: 2023-03-07
• Results First Posted: 2023-04-03
• Last Update Posted: 2023-04-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Histologically or cytologically confirmed head and neck squamous cell carcinoma.
2. Human papilloma virus (HPV) negative tumor.
3. Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate.
4. Prior treatment with cetuximab with tumor progression during or within 6 months after completing treatment.
5. Measurable disease.
6. Life expectancy ≥ 12 weeks.
7. 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.
8. Willingness to undergo a tumor biopsy prior to starting treatment (or if biopsy is not feasible, provide archival tissue).

Exclusion Criteria

1. Previous treatment with CDX-3379 or other anti-ErbB3 targeted agents.
2. Nasal, paranasal sinus, or nasopharyngeal carcinoma, aside from WHO Type I and II (keratinizing, non-EBV positive) nasopharyngeal carcinoma which will be allowed.
3. Major surgery within 4 weeks prior to first dose of study treatment.
4. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment.
5. Monoclonal based therapies within 4 weeks (excluding cetuximab) and all other immunotherapy within 2 weeks prior to first dose of study treatment.
6. 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.
7. Active, untreated central nervous system metastases.
8. Active autoimmune disease or documented history of autoimmune disease.
9. Significant cardiovascular disease including CHF or poorly controlled hypertension.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CDX-3379 and cetuximab	CDX-3379 and cetuximab	During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	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.	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	The time from start of study drug to death from any cause (up to approximately 2 years)	The time from start of study drug to death
Clinical Benefit Response (CBR)	Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years	The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks
Duration of Response (DOR)	First occurrence of a documented objective response to disease progression or death (up to approximately 2 years)	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
Progression-free Survival (PFS)	From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years)	The time from start of study drug to time of progression or death, whichever occurs first
Incidence of Adverse Events [Safety and Tolerability]	Following at least one dose of study treatment through 30 days after last dose of CDX-3379.	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.
Tumor DNA Biomarkers.	Tumor tissue is obtained during screening window via single biopsy procedure.	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.

Trial Locations

Locations (10)

University of Pennsylvania Hospital, Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

The University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Emory University Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Rush University Medical center; 🇺🇸 Chicago, Illinois, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States