Clinical Trial 18902

Cancer Type: Head & Neck
Interventions:Avelumab; MSB00100718C (Avelumab); Placebo; Radiotherapy; cisplatin

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Christine Chung

Overview

Study Title

A Randomized Double-Blind Phase 3 Study of Avelumab in Combination with Standard of Care Chemoradiotherapy (Cisplatin Plus Definitive Radiation Therapy) Versus Standard of Care Chemoradiotherapy in the Front-Line Treatment of Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Summary

The main purpose of this study is to compare the effects of the study drug, avelumab (MSB0010718C) in combination with standard of care (SOC) chemoradiotherapy to placebo in combination with SOC chemoradiotherapy. A placebo looks like the study drug but does not contain any drug. Researchers use a placebo to see if the study drug works better or is safer than not taking anything. The SOC chemoradiotherapy is a treatment normally used for treating patients with head and neck cancer; and the SOC chemoradiotherapy in this study will be cisplatin plus radiation therapy.

Objective

Primary Objective: - To demonstrate that treatment with avelumab in combination with SOC CRT is superior to SOC CRT alone in prolonging PFS in front-line patients with high risk (as defined in Inclusion Criterion 2 [Section 4.1]), locally advanced SCCHN who are candidates for definitive CRT with cisplatin. Secondary Objectives: - To compare the OS of avelumab in combination with SOC CRT vs SOC CRT alone. - To evaluate the anti-tumor activity of avelumab in combination with SOC CRT and SOC CRT alone. - To evaluate the overall safety and tolerability profile of of avelumab in combination with SOC CRT and SOC CRT alone. - To evaluate the PK of avelumab. - To evaluate the PK of cisplatin (total and free). - To assess avelumab ADAs. - To evaluate the effect of avelumab in combination with SOC CRT and SOC CRT alone on patient-reported outcomes (PROs) of disease-related symptoms and health-related quality of life. - To evaluate candidate immune-related predictive biomarkers of sensitivity or insensitivity to treatment with avelumab in combination with SOC CRT in pretreatment tumor samples (eg, PD-L1 expression). - To evaluate candidate immune-related predictive biomarkers of sensitivity or insensitivity to treatment with avelumab in combination with SOC CRT in tumor samples (eg, PD-L1 expression) after one dose of avelumab in patients who provide this optional biopsy. Exploratory Objectives: - To explore the predictive and/or pharmacodynamic (PD) characteristics of peripheral blood and additional tumor tissue biomarkers relevant to the mechanism of action of or insensitivity to the combined modality of avelumab in combination with SOC CRT. - To explore the relationship between the PET scan evaluation and the pathological evaluation of neck dissection. - To explore the effect of avelumab in combination with SOC CRT and SOC CRT alone on patient-reported outcomes of symptomatic AE.

Inclusion Criteria

  • Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx.
  • HPV negative disease, Stage III, IVa, IVb or Non oropharyngeal HPV positive disease, Stage III, IVa, IVb or HPV positive oropharyngeal disease T4, N2c, or N3.
  • No prior therapy for advanced stage squamous cell carcinomas of the head and neck (SCCHN); eligible for definitive CRT with curative intent.
  • Available tumor samples for submission or willing to undergo further tumor biopsies.
  • Age ≥18 years.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
  • Adequate bone marrow function.
  • Adequate renal function.
  • Adequate liver function.
  • Pregnancy test (for participants of childbearing potential) negative at screening.

  • Exclusion Criteria

  • Prior immunotherapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways.
  • Major surgery 4 weeks prior to randomization.
  • Diagnosis of any other malignancy within 5 years prior to randomization, except for superficial esophageal cancer (TIS or T1a) fully resected by endoscopy, prostate cancer (Gleason score ≤6) either curatively treated or deemed to not require treatment, ductal in situ carcinoma of the breast that has completed curative treatment, adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or bladder.
  • Active autoimmune disease.
  • Any of the following in the 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
  • Active infection requiring systemic therapy.
  • Use of immunosuppressive medication at time of randomization.
  • Prior organ transplantation including allogenic stem-cell transplantation.
  • Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  • Vaccination within 4 weeks prior to randomization.
  • Current use of or anticipated need for treatment with other anti-cancer drugs.
  • Females who are pregnant or breastfeeding. Males able to father children and females of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 60 days after the last dose of avelumab/placebo (whichever is later).