Clinical trial NCT03254927: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Advanced Head and Neck Squamous Cell Carcinoma
Keywords: Erbitux
Cetuximab
Oral Cancer
Oropharyngeal cancer
Laryngeal cancer
Head and Neck Squamous Cell Carcinoma
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-08-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: 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 outcomes:
measure: Clinical Benefit Response (CBR)
timeFrame: Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: First occurrence of a documented objective response to disease progression or death (up to approximately 2 years)
measure: Progression-free Survival (PFS)
timeFrame: From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years)
measure: Overall Survival (OS)
timeFrame: The time from start of study drug to death from any cause (up to approximately 2 years)
measure: Incidence of Adverse Events [Safety and Tolerability]
timeFrame: Following at least one dose of study treatment through 30 days after last dose of CDX-3379.
measure: Tumor DNA Biomarkers.
timeFrame: Tumor tissue is obtained during screening window via single biopsy procedure.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical center
state: Illinois
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital, Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
References:
citation: 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.