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

• Register: EUCTR
• Last refreshed on: 12 July 2021
• Main ID: EUCTR2014-003698-41-AT
• Date of registration: 02/02/2015
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co. Inc.
• Public title: Pembrolizumab as First Line Treatment in Subjects with Recurrent/Metastatic HNSCC.
• Scientific title: A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.
• Date of first enrolment: 10/03/2015
• Target sample size: 825
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003698-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Brazil, Canada, Chile, Colombia, Czech Republic, Czechia, Denmark, Estonia, Finland, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Latvia, Malaysia, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Have histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapies.
2. Be willing and able to provide documented informed consent for the trial. The subject may also provide consent for FBR. However, the
subject may participate in the main trial without participating in FBR.
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
7. Have results from testing of HPV status for oropharyngeal cancer defined as p16 IHC testing using CINtec® p16 Histology assay and a
70% cutoff point (please see Section 7.1.2.7 for details). If HPV status was previously tested using this method, no additional testing is
required.
8. Have provided tissue for PD-L1 biomarker analysis from a core or excisional biopsy (FNA is not adequate).
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 course of the study through 180 days after the last dose of study medication Subjects of childbearing potential are
those who have not been surgically sterilized or have not been free from menses for >1 year.
11. Male subjects should 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 650
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 175

Exclusion criteria:
1. Has disease that is suitable for local therapy administered with curative intent.
2. Has PD within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
3. Has had radiation therapy (or other nonsystemic therapy) within 2 weeks prior to randomization or subject has not fully recovered (i.e., =
Grade 1 or at baseline) from AEs due to a previously administered treatment.
4. 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.
5. Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g. tumor bleeding, uncontrolled tumor pain) in
the opinion of the treating investigator.
6. 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. Corticosteroid use as premedication for allergic reactions (e.g. IV contrast), or as a prophylactic management of AEs related to the chemotherapies specified in the protocol is allowed. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
7. Has a diagnosed and/or treated additional malignancy within 5 years prior to randomization with the exception of: curatively treated basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, curatively resected in situ cervical cancer, and curatively resected in situ breast
cancer. Other exceptions may be considered with Sponsor consultation.
8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
9. 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency, etc.) is not considered a form of systemic treatment.
10. Has had an allogeneic tissue/solid organ transplant.
11. Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis.
12. Has an active infection requiring systemic therapy.
13. 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.
14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
15. 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.
16. 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.
17. Has a known history of HIV (HIV 1/2 antibodies).
18. Has known active Hepatitis B or Hepatitis C .
19. Has received a live vaccine within 30 days of planned start of study therapy.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Recurrent/metastatic head and neck squamous cell carcinoma.
MedDRA version: 21.1 Level: PT Classification code 10071540 Term: Head and neck cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Pembrolizumab
Product Code: 1374853-91-4
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive name: Anti-PD-1 monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Carboplatin 10 mg/ml Intravenous Infusion
Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Other descriptive name: CARBOPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Fluorouracil-GRY
Product Name: Fluorouracil (5-fluorouracil)
Pharmaceutical Form: Injection
INN or Proposed INN: Fluorouracil
CAS Number: 51-21-8
Other descriptive name: FLUOROURACIL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Trade Name: Erbitux 5mg/ml
Product Name: Cetuximab (Erbitux)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CETUXIMAB
CAS Number: 205923-56-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Cisplatin 1 mg/ml concentrate for solution for infusion
Product Name: Cisplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Cisplatin
CAS Number: 15663-27-1
Other descriptive name: CISPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: Fluorouracil
Product Name: Fluorouracil (5-fluorouracil)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Fluorouracil
CAS Number: 51-21-8
Other descriptive name: FLUOROURACIL
Concentration

Primary Outcome(s)

Primary end point(s): - Progression-free survival (PFS) - RECIST 1.1 by BICR
- Overall Survival

Timepoint(s) of evaluation of this end point: 1. Progression-free-survival (PFS) is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first.
2. Overall Survival is defined as the time from randomization to death due to any cause. Subjects without documented death at the time of the final Analysis will be censored at the date of the last follow-up.

Main Objective: 1) To compare the Progression Free Survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR) in first line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) subjects, treated with pembrolizumab monotherapy versus standard treatment
2) To compare PFS per RECIST 1.1 as assessed by BICR in first line R/M HNSCC subjects, treated with pembrolizumab in combination with chemotherapy versus standard treatment.
3) To evaluate the overall survival (OS) in first line R/M HNSCC subjects, treated with pembrolizumab monotherapy versus standard treatment.
4) To evaluate OS in first line R/M HNSCC subjects, treated with pembrolizumab in combination with chemotherapy versus standard treatment.

Secondary Objective: 1) To evaluate the safety and tolerability profile of pembrolizumab monotherapy or a combination of pembrolizumab with chemotherapy in all first line R/M HNSCC subjects.
2) To evaluate proportion progression free at 6 and 12 months per RECIST 1.1 by BICR of first line R/M HNSCC subjects.
3) To evaluate ORR per RECIST 1.1 by BICR in first line R/M HNSCC subjects
4) To evaluate mean change from baseline in global health status/quality of life in first line R/M HNSCC subjects.
5) To evaluate time to deterioration (TTD) in global health status/quality of life, pain and swallowing in first line R/M HNSCC subjects.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Objective Response rate is defined as the Proportion of the subjects in the Analysis Population who have a complete Response (CR) or partial response (PR). Responses are based upon BICR per RECIST 1.1

Secondary end point(s): - Objective Response Rate (ORR) - RECIST 1.1 by BICR

Secondary ID(s)

2014-003698-41-SE

MK-3475-048

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Ethics review

Status: Approved
Approval date: 24/02/2015
Contact: