Description:
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.
Title
- Brief Title: A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma
- 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 IDs
- ORG STUDY ID:
CDX3379-04
- NCT ID:
NCT03254927
Conditions
- Advanced Head and Neck Squamous Cell Carcinoma
Interventions
| Drug | Synonyms | Arms |
|---|
| CDX-3379 and cetuximab | | CDX-3379 and cetuximab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| CDX-3379 and cetuximab | Experimental | During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression. | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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. |
| Safety Issue: | |
| Description: | The percentage of patients who achieve a complete response or partial response per RECIST 1.1 criteria. |
Secondary Outcome Measures
| Measure: | Clinical Benefit Response (CBR) |
| Time Frame: | Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years |
| Safety Issue: | |
| Description: | The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months |
| Measure: | Duration of response (DOR) |
| Time Frame: | First occurrence of a documented objective response to disease progression or death (up to approximately 2 years) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | 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) |
| Safety Issue: | |
| Description: | The time from start of study drug to time of progression or death, whichever occurs first |
| Measure: | Overall Survival (OS) |
| Time Frame: | The time from start of study drug to death from any cause (up to approximately 2 years) |
| Safety Issue: | |
| Description: | The time from start of study drug to death |
| Measure: | Incidence of drug related adverse events, serious drug related adverse events, dose-limiting toxicities and laboratory test abnormalities [Safety and Tolerability] |
| Time Frame: | Following at least one dose of study treatment through 30 days after last dose of CDX-3379. |
| Safety Issue: | |
| Description: | Safety and tolerability of CDX-3379 in combination with cetuximab as determined by vital sign measurements, clinical laboratory tests, physical exams, ECGs and the incidence and severity of adverse events. |
| Measure: | Pharmacokinetic evalution |
| Time Frame: | From start of study drug through 30 day follow up |
| Safety Issue: | |
| Description: | CDX-3379 serum concentration will be measured |
| Measure: | Immunogenicity evaulation |
| Time Frame: | Prior to each dose of study treatment through 30 day follow up |
| Safety Issue: | |
| Description: | Serum samples will be obtained for assessment of human anti-CDX-3379 antibodies |
| Measure: | Tumor DNA biomarkers. |
| Time Frame: | Tumor tissue is obtained during screening window via single biopsy procedure. |
| Safety Issue: | |
| Description: | Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Celldex Therapeutics |
Trial Keywords
- Erbitux
- Cetuximab
- Oral Cancer
- Oropharyngeal cancer
- Laryngeal cancer
- Head and Neck Squamous Cell Carcinoma
Last Updated
April 28, 2021
