Sponsor decision based on emerging risk-benefit profile

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.

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.

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.