Conditions: Carcinoma, Squamous Cell of Head and Neck
Keywords: SCCHN HNSCC
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 195
Healthy volunteers: no

Brief summary:
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.

Detailed description:
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.

Arms:
arm 1: VTX-2337 (3.0 mg/m2) will be administered on Day 8 and Day 15 of a 21-day cycle for 6 cycles, followed by dosing on Days 8 and 22 of 28-day cycles until disease progression.

Cisplatin (100 mg/m2) OR carboplatin (AUC 5 mg/mL/min) will be administered on Day 1 of a 21-day cycle for a maximum of 6 cycles.

5-FU (1000 mg/m2) will be administered on Days 1-4 of a 21-day cycle for a maximum of 6 cycles.

Cetuximab (initial dose: 400 mg/m2; remaining doses: 250 mg/m2) will be administered weekly until disease progression. arm 2: Placebo (3.0 mg/m2) will be administered on Day 8 and Day 15 of a 21-day cycle for 6 cycles, followed by dosing on Days 8 and 22 of 28-day cycles until disease progression.

Cisplatin (100 mg/m2) OR carboplatin (AUC 5 mg/mL/min) will be administered on Day 1 of a 21-day cycle for a maximum of 6 cycles.

5-FU (1000 mg/m2) will be administered on Days 1-4 of a 21-day cycle for a maximum of 6 cycles.

Cetuximab (initial dose: 400 mg/m2; remaining doses: 250 mg/m2) will be administered weekly until disease progression.

Interventions: intervention 1: VTX-2337 intervention 2: Carboplatin intervention 3: Cisplatin intervention 4: 5-fluorouracil intervention 5: Placebo
Intervention descriptions: intervention 1: TLR8 Agonist intervention 2: None intervention 3: None intervention 4: None intervention 5: None

Protocol document: