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

NCT ID: NCT03254927

Last Updated: 2023-04-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-27
• Study Completion Date: 2020-12-16

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.

Conditions

Advanced Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CDX-3379 and cetuximab

During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.

Group Type: EXPERIMENTAL

CDX-3379 and cetuximab

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celldex Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Rush University Medical center

Chicago, Illinois, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Cincinnati

Cincinnati, Ohio, United States

University of Pennsylvania Hospital, Abramson Cancer Center

Philadelphia, Pennsylvania, United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

Duvvuri U, George J, Kim S, Alvarado D, Neumeister VM, Chenna A, Gedrich R, Hawthorne T, LaVallee T, Grandis JR, Bauman JE. Molecular and Clinical Activity of CDX-3379, an Anti-ErbB3 Monoclonal Antibody, in Head and Neck Squamous Cell Carcinoma Patients. Clin Cancer Res. 2019 Oct 1;25(19):5752-5758. doi: 10.1158/1078-0432.CCR-18-3453. Epub 2019 Jul 15.

Reference Type: DERIVED

PMID: 31308059 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CDX3379-04

Identifier Type: -

Identifier Source: org_study_id