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

March 7, 2023 updated by: Celldex Therapeutics

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • The University of Arizona Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Yale Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Winship Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Hospital, Abramson Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CDX-3379 and cetuximab
During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: 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.
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
Progression-free Survival (PFS)
Time Frame: 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
From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years)
Overall Survival (OS)
Time Frame: 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
The time from start of study drug to death from any cause (up to approximately 2 years)
Clinical Benefit Response (CBR)
Time Frame: 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
Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years
Duration of Response (DOR)
Time Frame: 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
First occurrence of a documented objective response to disease progression or death (up to approximately 2 years)
Incidence of Adverse Events [Safety and Tolerability]
Time Frame: 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.
Following at least one dose of study treatment through 30 days after last dose of CDX-3379.
Tumor DNA Biomarkers.
Time Frame: 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.
Tumor tissue is obtained during screening window via single biopsy procedure.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celldex Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 27, 2018

Primary Completion (Actual)

September 16, 2020

Study Completion (Actual)

December 16, 2020

Study Registration Dates

First Submitted

August 17, 2017

First Submitted That Met QC Criteria

August 17, 2017

First Posted (Actual)

August 21, 2017

Study Record Updates

Last Update Posted (Actual)

April 3, 2023

Last Update Submitted That Met QC Criteria

March 7, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDX3379-04

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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