Ph 3 Trial of MK-3475 (Pembrolizumab) vs Standard Treatment in Recurrent/Metastatic Head and Neck Cancer

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2014-001749-26-LT
• Date of registration: 04/09/2014
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Ph 3 Trial of MK-3475 (Pembrolizumab) vs Standard Treatment in Recurrent/Metastatic Head and Neck Cancer
• Scientific title: A Phase III Randomized Trial of MK-3475 (Pembrolizumab) versus Standard Treatment in Subjects with Recurrent or Metastatic Head and Neck Cancer - Ph 3 Trial of MK-3475 (Pembrolizumab) vs Standard Treatment in Recurrent/Metastatic Head and Neck Ca
• Date of first enrolment: 05/11/2014
• Target sample size: 466
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001749-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Hungary, Ireland, Italy, Korea, Republic of, Lithuania, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Global Clinical Trials Operations
• Affiliation: UAB Merck Sharp & Dohme

• Name: Global Clinical Trials Operations
• Affiliation: UAB Merck Sharp & Dohme

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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.
2. Be > 18 years of age on day of signing informed consent.
3. Have histologically or cytologically-confirmed recurrent disease that is not amenable to curative treatment with local and/ or systemic therapies) or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies. Subjects may not have any other primary tumor site (e.g. nasopharynx).
4. Prior platinum failure as defined by, either:
a. Disease progression after treatment with a platinum-containing regimen for recurrent (disease not amenable to curative treatment) /metastatic disease.
Note: Disease progression may occur at any time during or after a platinum-containing regimen (e.g. carboplatin or cisplatin) which was administered in either 1L or 2L in the recurrent/metastatic setting.
OR
b. Recurrence/progression within 6 months of prior multimodal therapy using platinum (e.g. locally advanced setting).
5. 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. If HPV status has previously been tested using the procedure, no retesting is required.
Note: HPV stratification in this trial will be performed using local testing of HPV status in patients with oropharynx cancer. Oral cavity, hypopharynx, and larynx cancer are not required to undergo HPV testing by p16 IHC as by convention assumed to be HPV negative.
6. Have provided tissue for PD-L1 biomarker analysis - and received the PD-L1 results - (PD-L1 analysis will be blinded to both site and sponsor) from a newly obtained core or excisional biopsy. Repeat samples may be required if adequate tissue is not provided or for indeterminate results.
Note: Patients 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.
Note: If emerging data indicate a high concordance in PD-L1 expression scores between newly obtained and archival samples, archived samples may be acceptable.
7. Have radiographically 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.
8. Have a performance status of 0 or 1 on the ECOG Performance Scale, as assessed within 10 days of treatment initiation.
9. Demonstrate adequate organ function as defined in Table 1 of the protocol, all screening labs should be performed within 10 days of treatment initiation.
10. Female subjects of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication. A urine test can be considered if a serum test is not appropriate.
11. 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 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically steri
Exclusion criteria:
1. Has disease that is suitable for local therapy administered with curative intent.
2. Had progressive disease within three months of completion of curatively intended treatment for locoregionally advanced or recurrent HNSCC.
Note: This exclusion criterion is only applicable for subjects who have not had treatment in the metastatic/recurrent setting.
3. Is currently participating in and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to randomization.
Note: Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since the last dose of previous investigational agent or device.
4. Was previously treated with 3 or more systemic regimens given for recurrent and/ or metastatic disease.
5. Patients previously treated or resistant to one of the 3 standard of care agents in this trial (i.e. docetaxel, methotrexate or cetuximab) may not receive the same agent if randomized to the standard treatment arm
{see Section 5.2 for details).
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. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
7. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
8. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent.
Note: Subjects with = Grade 2 neuropathy or = Grade 2 alopecia are an exception to this criterion and may qualify for the study.
Note: If subject received major surgery, they must have recovered adequately from the toxicity and/ or complications from the intervention prior to starting therapy.
9. Has 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 and/or curatively resected in situ cervical and/or breast cancers.
10. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four 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.
11. Has active autoimmune disease that has required systemic treatment past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs. Replacement theraphy (e.g., thyroxinie, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is permitted.
12. Has active, non-infectious pneumonitis.
13. Has an active infection requiring systemic therapy.
14. Has a history

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

Health Condition(s) or Problem(s) studied

Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
MedDRA version: 19.0 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: MK-3475; SCH900475; 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: Methotrexate
Product Name: Methotrexate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Methotrexate
Product Name: Methotrexate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Methotrexate
Product Name: Methotrexate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Methotrexate
Product Name: Methotrexate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Docetaxel
Product Name: Docetaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Docetaxel
CAS Number: 114977-28-5
Other descriptive name: DOCETAXEL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Erbitux (Cetuximab)
Product Name: Cetuximab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CETUXIMAB
CAS Number: 205923-56-4
Other descriptive na

Primary Outcome(s)

Secondary Objective: PD-L1 Positive Population
1. To compare Overall Survival (OS) in subjects with R/M HNSCC treated with pembrolizumab compared to standard treatment.
2. To compare ORR per RECIST 1.1 as assessed by blinded independent radiology review in subjects with R/M HNSCC treated with pembrolizumab compared to standard treatment.
3. To compare PFS per RECIST 1.1 as assessed by blinded independent radiology review in subjects with R/M HNSCC treated with pembrolizumab compared to standard treatment.

All subjects (regardless of PD-L1 expression)
4. To compare ORR per RECIST 1.1 as assessed by blinded independent radiology review in subjects with R/M HNSCC treated with pembrolizumab compared to standard treatment.
5. To compare PFS per RECIST 1.1 as assessed by blinded independent radiology review in subjects with R/M HNSCC treated with pembrolizumab compared to standard treatment.

Timepoint(s) of evaluation of this end point: The final OS analysis will be conducted after ~340 deaths have occurred between the MK-3475 arm and the standard treatment arm.

Main Objective: To compare the overall survival (OS) in subjects with R/M HNSCC treated with pembrolizumab compared to standard treatment.

Primary end point(s): Overall Survival (OS) 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.

Secondary Outcome(s)

Secondary end point(s): - OS in subjects with PD-L1 1% CPS
- ORR per RECIST 1.1 in all subjects
- ORR per RECIST 1.1 in subjects with PD-L1 1% CPS
- Progression-free-survival (PFS) per RECIST 1.1 in all subjects
- PFS per RECIST 1.1 in subjects with PD-L1 1% CPS

Timepoint(s) of evaluation of this end point: -The timing of the evaluation of the secondary endpoints will be driven by and the same as the timing of the evaluation of the primary endpoint.

Secondary ID(s)

2014-001749-26-IE

MK-3475-040

Source(s) of Monetary Support

Source of Monetary or Material Support Organisation Name: Merck Sharp & Dohme Corp, a subsidiary of Merck &Co Inc