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

• Register: EUCTR
• Last refreshed on: 18 September 2023
• Main ID: EUCTR2014-003698-41-LV
• Date of registration: 23/01/2015
• 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: 13/03/2015
• Target sample size: 825
• Recruitment status: Not Recruiting
• 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

Key inclusion & exclusion criteria

Inclusion criteria:
- Have histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapies.
- Have measurable disease based on RECIST 1.1 as determined by the site.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Have results from local testing of HPV positivity for oropharyngeal cancer defined as p16 IHC testing using CINtec® p16 Histology assay and a 70% cut off point.
- Have provided tissue for PD-L1 biomarker analysis from a core or excisional biopsy. Repeat samples may be required if adequate tissue is not provided. A newly obtained biopsy (within 90 days prior to start of study treatment) is strongly preferred, but an archival sample is acceptable.

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:
- Has disease that is suitable for local therapy administered with curative intent.
- Has progressive disease within six months of completion of curatively intended treatment for locoregionally advanced HNSCC.
- Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or not fully recovered from AE due to previous treatment.
- 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.
- 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 pre-medication for allergic reactions (e.g. IV contrast), or as a prophylactic management of adverse events related to the chemotherapies specified in the protocol is allowed.
- Has a known history of prior malignancy with recurrence in the last 5 years.
- Active autoimmune disease that has required systemic treatment in past 2 years.
- Has had an allogeneic tissue/solid organ transplan.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- 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.
- Has an active infection requiring systemic therapy.



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

Health Condition(s) or Problem(s) studied

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)

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

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
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Fluorouracil
CAS Number: 51-21-8
Other descriptive name: FLUOROURACIL
Concentration unit: mg/ml millig

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Progression-free-survival 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 a subgroup of 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 all 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, tretaed with pembrolizumab monotherapy versus standard treatment.
4) To evaluate the OS in all first line R/M HNSCC subjects, treated with pembrolizumab in combination with chemotherapy versus standard treatment.

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

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: 1. The proportion progression free at 6 months and at 12 months is defined as the Kaplan-Meier estimate of the survival function for PFS at 6 months and 12 months, respectively. The progression-free status is based upon BICR per RECIST 1.1.
2. 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.
3. For subjects who demonstrated CR or PR, duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death, whichever occurs first.

Secondary end point(s): - Proportion progression free at 6 months and 12 months – RECIST 1.1 by BICR
- Objective Response Rate (ORR) – RECIST 1.1 by BICR
- Duration of Response (DOR) – 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: 30/01/2015
Contact: