Pembrolizumab as First Line Treatment in Subjects with Recurrent/Metastatic HNSCC.

• Conditions: Recurrent/metastatic head and neck squamous cell carcinoma.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-003698-41-ES
• Lead Sponsor: Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co. Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-03-03
• Last Update Posted: 7 December 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 750

Inclusion Criteria

1. Have histologically or cytologically-confirmed R/M HNSCC that is considered
incurable by local therapies.
-Subjects may not have had prior systemic therapy administered in the
recurrent or metastatic setting. Systemic therapy which was completed more
than 6 months prior to signing consent if given as part of multimodal
treatment for locally advanced disease is allowed.
- The eligible primary tumor locations are oropharynx, oral cavity,
hypopharynx, and larynx.
- Subjects may not have a primary tumor site of nasopharynx (any histology).
2. Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
3. Be ?18 years of age on day of signing informed consent.
4. Have measurable disease based on RECIST 1.1 as determined by the site. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
5. Have a performance status of 0 or 1 on the ECOG Performance Scale.
6. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
7. Have results from local testing of HPV positivity for oropharyngeal cancer defined as p16 IHC testing using CINtec® p16 Histology assay and a 70% cutoff point.
Note: Tumor p16 expression must be evaluated by means of IHC analysis with
CINtec® p16 Histology assay (Ventana Medical Systems Inc., Tucson AZ) using
?Benchmark Ultra? autostainer (Ventana, Tucson, AZ) and standard
protocol. Positive p16 expression is defined as strong and diffuse nuclear and
cytoplasmic staining in 70% or more of the tumor cells.
Note: HPV stratification in this trial will be performed using local testing of HPV
status in patients with oropharynx cancer.
Note: Oral cavity, hypopharynx, and larynx cancer are not required to undergo
HPV testing by p16 IHC as by convention assumed to be HPV negative.
8. Have provided tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate (FNA) is not adequate). Repeat samples may be required if adequate tissue is not provided. This specimen may be the diagnostic sample for patients with a new diagnosis of metastatic HNSCC. If obtained for a patient with recurrent disease for locally advanced disease, then it must be obtained after completion of the previous initial management with no other treatment from the time of biopsy until the start of study treatment. Refer to Section 7.1.2.7 for more information on the tissue sample collection.
Note: Subjects for whom newly obtained samples cannot be obtained (e.g.
inaccessible or patient safety concern) may submit an archived specimen only
upon agreement from the Sponsor. Newly obtained tissue must be obtained up to 90 days prior to treatment initiation.
Note: If emerging data indicate a high concordance in PD-L1 expression scores
between newly obtained and archival samples, archived samples may be
acceptable.
9. Female subjects of childbearing potential should have a negative blood pregnancy test within 72 hours prior to receiving the first dose of study medication. A urine test can be considered if a blood test is not appropriate.
10. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the

Exclusion Criteria

1. Has disease that is suitable for local therapy administered with curative intent.
2. Has progressive disease within six months of completion of curatively intended treatment for locoregionally advanced HNSCC.
3. Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy, or used an investigational device, any of which occurred within 4 weeks of the first dose of treatment.
Note: Participation in the follow-up phase (receiving no study treatment) of a prior study is allowed.
4. 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. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer with no evidence of that disease recurrence for 5 years since initiation of that therapy.
Note: The time requirement for no evidence of disease for 5 years does not apply to the tumor for which a subject is enrolled in the trial.
6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging (using the identical imaging modality for each assessment, either MRI or CT scan) for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
7. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
8. Has evidence of active, non-infectious pneumonitis.
9. Has an active infection requiring systemic therapy.
10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
12. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of trial treatment.
13. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in Merck MK-3475 clinical trials.
14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detecte

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified