Pembrolizumab or placebo in combination with chemoradiation (CRT) in subjects with locally advanced HNSCC

Recruitment & Eligibility

Status: completed

Sex: All

Target Recruitment: 780

Inclusion Criteria

1) Have a pathologically proven new diagnosis of squamous cell carcinoma below:
a. Oropharyngeal p16 positive OR b. Oropharyngeal p16 negative OR c. Larynx/hypopharynx/oral cavity (independent of p16)
Note: Subjects with oral cavity tumors need to have unresectable disease.
2) Have provided tissue for PD-L1 biomarker analysis from a core or excisional biopsy.
3) Have evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by CT scan or MRI, based on RECIST version 1.1.
4) Be eligible for definitive CRT and not considered for primary surgery based on investigator decision.
5) Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 performed within 10 days of treatment initiation.
6) Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial treatment.
7) Male and Female subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 180 days after the last dose of study therapy.

Exclusion Criteria

1) Has current participation or treatment with an investigational agent or use of an investigational device within 4 weeks of the first dose of trial treatment.
2) Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137 or other immune checkpoint inhibitors) or has previously participated in MK-3475 clinical trials.
3) Has received a live vaccine within 30 days prior to the first dose of study treatment.
4) Has cancer outside of the oropharynx, larynx, hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer.
5) Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical surgery for the head and neck cancer under study.
6) If subject has received major surgery, and the subject has not recovered adequately from the toxicity and/or complications from the intervention prior to starting trial treatment.
7) Has known active Hepatitis B or C.
8) Has known history of Human Immunodeficiency Virus (HIV).
9) Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
10) Has a history of (non-infectious) pneumonitis/ interstitial lung disease that required steroids or current pneumonitis.Pneumonitis / interstitial lung disease is including radiation pneumonitis.
11) Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
12) Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization.
13) Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
14) Has had previous allogeneic tissue/solid organ transplant.
15) Has active infection requiring systemic therapy.
16) Has a history of severe hypersensitivity reaction to pembrolizumab, cisplatin or radiotherapy or their analogs.
17) Is a female subject who is pregnant or breast feeding or expecting to conceive or a male expecting to father children within the projected treatment phase of the trial, starting with the screening visit through 180 days after the last dose of trial treatment.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Event-Free Survival (EFS) [Time Frame: Up to 5 years]<br>The primary hypotheses for EFS is defined as the time from the date of randomization to the date of first record of any of the following events:<br>1)Progression per RECIST 1.1 by BICR OR 2)Biopsy as indicated for Locoregional progression or recurrence or Distant metastasis. Surgery. OR 3) Death due to any cause.

Secondary Outcome Measures

Name	Time	Method
- Overall Survival (OS)<br>- Adverse Events (AEs)<br>- Treatment Discontinuations due to AEs<br>- Change from baseline in Global health status/QoL and physical functioning using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30)<br>- Change from baseline in swallowing, speech and pain symptoms using the EORTC Head and Neck Questionnaire (EORTC QLQ-H&N35)

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