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

Advanced Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03254927
• Other study ID #: CDX3379-04
• Status: Terminated
• Phase: Phase 2
• Start date: March 27, 2018
• Est. completion date: December 16, 2020

Study information

• Verified date: March 2023
• Source: Celldex Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: December 16, 2020
• Est. primary completion date: September 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Head and Neck Squamous Cell Carcinoma
• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• CDX-3379 and cetuximab
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.

Locations

Country	Name	City	State
United States	Emory University Winship Cancer Institute	Atlanta	Georgia
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rush University Medical center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	University of Pennsylvania Hospital, Abramson Cancer Center	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	The University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Celldex Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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.
Secondary	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.