Clinical Trials Register

Summary
EudraCT Number:	2017-000594-37
Sponsor's Protocol Code Number:	MK-3475-629
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-04-27
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2017-000594-37

A.3

Full title of the trial

A Phase 2, Open-label, Single arm Study to Evaluate the Safety and Efficacy of Pembrolizumab in Participants with Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (R/M cSCC)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase II, Open-labeled, Single arm Study to Evaluate the Safety and Efficacy of Pembrolizumab in Participants with Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma

A.3.2

Name or abbreviated title of the trial where available

Phase 2 Study of Pembrolizumab in Participants With R/M cSCC

A.4.1

Sponsor's protocol code number

MK-3475-629

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme (UK) Ltd.
B.5.2	Functional name of contact point	Global Clinical Trial Operations
B.5.3	Address:
B.5.3.1	Street Address	Hertford road
B.5.3.2	Town/ city	Hoddesdon, Hertfordshire
B.5.3.3	Post code	EN11 9BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 (0)7969 847981
B.5.5	Fax number	+44 (0)1992 705241
B.5.6	E-mail	marie.pullen@msd.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Pembrolizumab
D.3.2	Product code	MK-3475
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEMBROLIZUMAB
D.3.9.1	CAS number	1374853-91-4
D.3.9.2	Current sponsor code	MK-3475
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Recurrent or Metastatic (R/M) Cutaneous Squamous Cell Carcinoma (cSCC) or locally advanced (LA) unresectable cSCC.

E.1.1.1

Medical condition in easily understood language

Cutaneous squamous cell carcinoma

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10041834
E.1.2	Term	Squamous cell carcinoma of skin
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To estimate the ORR per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR)

E.2.2

Secondary objectives of the trial

1. To evaluate the duration of response (DOR) per RECIST 1.1 as assessed by BICR
2. To evaluate the disease control rate (DCR) per RECIST 1.1 as assessed by BICR
3. To evaluate the progression-free survival (PFS) per RECIST 1.1 as assessed by BICR
4. To evaluate the overall survival (OS) of the participants
5. To determinate the safety and tolerability of pembrolizumab in study participants with R/M cSCC

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Merck will conduct Future Biomedical Research on DNA (Blood, serum/plasma and tissue) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.

E.3

Principal inclusion criteria

1.R/M disease cohort only-All participants must have cSCC that is either metastatic, defined as disseminated disease, and/or unresectable disease that is not curable by surgery or radiation.
2.Participants must have histologically confirmed cSCC as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted)
3. LA disease cohort only – Participants must be ineligible for surgical resection.
4. LA disease cohort only – Participants who received prior radiation therapy(RT) to index site or must be deemed to be not eligible for RT.
5. LA disease cohort only – Participants who received prior systemic therapy for curative intent are eligible regardless of regimen.
6.R/M disease cohort only–Participants must have metastatic disease, defined as disseminated disease distant to the initial/primary site of diagnosis, and/or must have locally recurrent disease that has been previously treated (with either surgery or radiotherapy) and is not curable by either surgery or radiotherapy.
7.Participants must have measurable disease based on RECIST 1.1 as assessed by the central imaging vendor. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
8.Participants must have e an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days prior to the start of treatment
9.Participants must have adequate organ function as defined in the protocol.Specimens must be collected within 10 days prior to the start of treatment
10.Participants must have a tissue sample adequate for PD-L1 testing as determined by central laboratory testing prior to trial allocation. This tissue sample may be obtained from either a newly obtained core or excisional biopsy, or a prior archival tissue specimen
11.Participants must have a life expectancy of greater than 3 months
12. Be at least 18 years of age on the day of signing the informed consent.
13.Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
14.A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to use an adequate method of contraception as detailed in the protocol, during the treatment period and for at least 120 days after the last dose of study treatment
15.The participant (or legally acceptable representative if applicable) must be willing and able to provide written informed consent for the trial. The participant may also provide consent for Future Biomedical Research. However the participant may participate in the main trial without participating in Future Biomedical Research

E.4

Principal exclusion criteria

1.Participant has cSCC that can be cured with surgical resection, radiotherapy, or with a combination of surgery and radiotherapy.
2.Participant has any other histologic type of skin cancer other than invasive squamous cell carcinoma as the primary disease under study, eg, basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen’s disease, MCC, melanoma
3.Participants with any prior allogeneic solid organ or bone marrow transplantations are excluded
4.Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (eg, CTLA-4, OX-40, CD137)
5.Participant has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation
6.Participant has received prior radiotherapy within 2 weeks of start of trial treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease
7.Participant has received a live vaccine within 30 days prior to the first dose of trial drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killedvirus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live- attenuated vaccines and are not allowed
8.Participant is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment
9.Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug
10 Participant has a diagnosis and/or has been treated for additional malignancy within the past 5 years prior to allocation
11.Participant has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 7 days prior to first dose of trial treatment
12. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
13.Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (eg, with use of disease-modifying agents, anticoagulants, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
14.Participant has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
15.Participant has an active infection requiring systemic therapy
16.Participant has a known history of human immunodeficiency virus (HIV) infection
17.Participant has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
18.Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
19.Participant has a known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the trial
20.Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment

E.5 End points

E.5.1

Primary end point(s)

Objective response: defined as complete response (CR) or partial response (PR).

E.5.1.1

Timepoint(s) of evaluation of this end point

Imaging assessment will start at 6 weeks from the date of treatment allocation and continuing at the protocol specified timepoints. The patient would continue until the participant meets one of the criteria specified in the protocol to discontinue imaging

E.5.2

Secondary end point(s)

(1) DOR: for participants who demonstrate CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
(2) Disease control: defined as CR or PR or stable disease (SD) for at least 12 weeks.
(3) PFS: defined as the time from first day of study treatment to the first documented disease progression or death due to any cause, whichever occurs first.
(4) OS: defined as the time from first day of study treatment to death due to any cause.
(5) Adverse events (AEs). Study drug discontinuations due to AEs.

E.5.2.1

Timepoint(s) of evaluation of this end point

DOR/DCR/PFS: Imaging will be performed at the same timepoints as for the primary endpoint.
ALL: Periodic data monitoring will be performed by the sponsor. The timing of interim analyses and the final analysis will be documented in the supplementary Statistical Analysis Plan (sSAP). The sSAP will also be updated as the trial evolves. Participants will continue to be followed after the final analysis until the overall trial ends.
Safety: From the time of treatment allocation/randomization through 30 days (AEs) or 90 days (serious AEs) following cessation of study treatment.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

France

Germany

Israel

Mexico

Norway

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1