The purpose of this study is to compare the progression-free survival of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with VTX-2337 + cisplatin or carboplatin + 5-FU + cetuximab versus patients treated with cisplatin or carboplatin + 5-FU + cetuximab alone (standard-of-care; SOC). Safety and overall survival will also be evaluated.

This is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of VTX 2337 in combination with cisplatin or carboplatin, 5-FU and cetuximab in prolonging the progression-free survival in subjects with recurrent or metastatic squamous cell carcinoma of the head and neck.

OBJECTIVES:

Primary Objective:

To compare the efficacy of VTX 2337 plus SOC to SOC alone in prolonging the PFS of patients with recurrent or metastatic SCCHN using irRECIST evaluated by independent radiology review.

Secondary Objectives:

To compare the following between the two treatment groups:

• Safety of VTX 2337 by adverse events, including clinically significant changes in physical examination, peripheral blood hematology, serum chemistry, urinalysis, and ECG.
• Efficacy of VTX 2337 plus SOC in prolonging the OS of patients with recurrent or metastatic SCCHN.
• Efficacy of VTX-2337 plus SOC on ORR, DOBR, DCR, and DDC by irRECIST and evaluation by independent radiology review.
• Efficacy of VTX-2337 plus SOC on ORR, DOBR, DCR, and DDC by RECIST v1.1 and evaluation by independent radiology review.
• Efficacy of VTX 2337 plus SOC to SOC alone in prolonging the PFS by RECIST v1.1 and evaluation by independent radiology review.
• Efficacy of VTX 2337 plus SOC to SOC alone in prolonging the PFS by irRECIST and evaluation by investigators.

Exploratory Objectives:

• To compare genetic polymorphisms that may impact the response of patients to a TLR8 agonist or to cetuximab between the two treatment groups.
• To compare immune biomarker response to VTX 2337 plus SOC as measured by a multiplexed panel of cytokines, chemokines, and inflammatory markers between the two treatment groups.
• To compare the effect of immune cell subsets within the tumor on response to VTX-2337 and/or clinical outcome, as measured by immunohistochemistry in primary tumor tissue between the two treatment groups.
• To assess the PK of VTX-2337.

OUTLINE:

Subjects will be screened for eligibility (within 14 days) and qualified subjects will be randomized 1:1 to 1 of 2 treatment groups: SOC + VTX 2337 or SOC + placebo.

Tumor assessments will be by CT or MRI starting at Week 12 (± 3 days), then at Week 18 (± 3 days) and every 8 weeks (± 7 days) thereafter. Response will be evaluated by immune-related RECIST criteria (irRECIST) and confirmed by an independent radiologist.

Upon independent confirmation of disease progression, active participation in the study is complete and subjects will undergo the End of Treatment evaluations.

Subjects will be followed for survival until ~12 months after the last subject is randomized.

Inclusion Criteria:

• Ability and willingness to provide written informed consent
• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
• Locoregionally recurrent or metastatic disease that has not previously been treated with systemic therapy of recurrent or metastatic disease
• At least one measurable lesion on screening CT or MRI
• 18 years of age or older
• ECOG performance status of 0 or 1
• Acceptable bone marrow, renal, and hepatic function based upon screening lab tests
• Willingness to use medically acceptable contraception
• For females with reproductive potential: a negative serum pregnancy test

Exclusion Criteria:

• Disease which is amenable to curative local therapy
• Nasopharyngeal, salivary gland, lip or sinonasal carcinoma
• Surgery or irradiation ≤ 4 weeks prior to randomization
• Prior systemic anti-cancer therapy, unless administered for localized SCCHN and completed at least 6 months prior to disease recurrence
• Treatment with an investigational agent ≤ 30 days prior to randomization
• Treatment with corticosteroids within 2 weeks
• A requirement for chronic systemic immunosuppressive therapy for any reason
• Prior serious infusion reaction to cetuximab
• Treatment with an immunotherapy within 30 days
• Known brain metastases, unless stable for at least 28 days
• Active autoimmune disease currently requiring therapy
• Known infection with HIV
• Significant cardiac disease within 6 months
• Pregnant or breast-feeding females
• History of another primary malignancy, with the exception of (i) curatively resected non-melanoma skin cancer, (ii) curatively treated in situ cervical cancer, or (iii) other malignancy curatively treated with no evidence of disease and no anticancer therapy administered for 3 years prior to randomization, with the exception of adjuvant hormonal therapy for breast cancer
• Other conditions or circumstances that could interfere with the study