A Randomized, Double-Blind, Placebo-Controlled Study of Chemotherapy Plus Cetuximab in Combination with VTX-2337 in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
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.
Subjects will be screened for eligibility and qualified subjects will be randomized 1:1 to 1 of 2 treatment groups:
[?] SoC + VTX-2337
[?] SoC + placebo
Following the screening period, qualified subjects will be randomized in a 1:1 ratio to receive SoC plus placebo or SoC plus VTX-2337. Randomization of all subjects will be stratified by receipt of prior chemotherapy (yes or no), eCoG performance status (0 or 1), and platinum therapy as assigned by the investigator at the time of randomization (cisplatin or carboplatin).
Subjects will then be administered cisplatin or carboplatin-as assigned by the investigator prior to randomization-5-Fu, cetuximab, and iP (i.e., VTX-2337 or placebo) on pre-specified days of a 21-day cycle for 6 cycles ([Section]6.0). Thereafter, subjects will continue on study for cycles 7+ for dosing of weekly cetuximab and biweekly iP in 28-day cycles.
Subjects will be evaluated for PFS according to immune-related Response evaluation Criteria in Solid Tumors (irReCiST; [Section]18.104.22.168) at Week 12 ((+-) 3 days), Week 18 ((+-) 3 days), and every 8 weeks ((+-) 7 days) thereafter. Treatment will be discontinued for subjects with independently-confirmed radiographic disease progression. upon discontinuation of treatment, subjects will complete the end of Treatment visit and will be followed for survival.
VTX-2337 or placebo (investigational product; iP) will be administered as a subcutaneous injection on Day 8 and Day 15 of a 21-day cycle at a dose level of 3.0 mg/m2 for 6 cycles, followed by dosing on Days 8 and 22 of a 28-day cycle for cycles 7 and beyond. iP will be administered until disease progression.
1) Ability and willingness to provide written informed consent and to comply with the study[Single Quote]s visit and assessment schedule
2) Prior documentation of histologically or cytologically confirmed squamous cell carcinoma of the head and neck. Patients with squamous cell carcinoma of an unknown primary are eligible provided they previously received treatment for their locoregional head and neck cancer.
3) Locoregionally recurrent or metastatic SCCHN that has not previously been treated with systemic therapy for recurrent or metastatic disease
4) At least one measurable lesion as defined by RECIST v1.1 on screening computed tomography (CT) or magnetic resonance imaging (MRI)
5) 18 years of age or older
6) ECOG performance status of 0 or 1
7) Acceptable bone marrow, renal, and hepatic function based upon screening lab tests as demonstrated by the following:
[?] White blood cell (WBC) count > 2,500 cells/[?]l
[?] Absolute neutrophil count (ANC) > 1,500 cells/[MICRO-SYMBOL]L
[?] Platelet count >= 100,000 cells/[MICRO-SYMBOL]L
[?] Hemoglobin >= 9 g/dL
[?] Creatinine <= ULN OR Creatinine Clearance >= 60 mL/min
[?] Total bilirubin <= 2.0 x ULN
[?] SGOT (AST), SGPT (ALT) <= 2.5 x ULN or <= 5 x ULN in presence of liver metastases
[?] Potassium >= LLN
8) Willingness to use medically acceptable contraception throughout the study period and for 4 weeks after the final administration of IP
9) For female subjects with reproductive potential: a negative serum pregnancy test