Clinical Trials Register

Summary
EudraCT Number:	2017-003636-36
Sponsor's Protocol Code Number:	UCL/17/0396
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:	2018-09-12
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

2017-003636-36

A.3

Full title of the trial

A phase II trial to assess the efficacy and safety profile of pembrolizumab in patients with performance status 2 with recurrent or metastatic squamous cell carcinoma of the head and neck

A.3.1

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

Assessing safety and efficacy of pembrolizumab in patients with head and neck cancer.

A.3.2

Name or abbreviated title of the trial where available

POPPY

A.4.1

Sponsor's protocol code number

UCL/17/0396

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	University College London
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-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 Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CR UK & UCL Cancer Trials Centre
B.5.2	Functional name of contact point	POPPY Trial Coordinator
B.5.3	Address:
B.5.3.1	Street Address	90 Tottenham Court Road
B.5.3.3	Post code	W1T 4TJ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02076799392
B.5.5	Fax number	02076799871
B.5.6	E-mail	ctc.poppy@ucl.ac.uk

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.2.1.1.1	Trade name	Pembrolizumab
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V.
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.9.3	Other descriptive name	Anti-PD-1 monoclonal antibody
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.3.11.13.1	Other medicinal product type	monoclonal antibody
D.IMP: 2
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	Yes
D.2.1.1.1	Trade name	KEYTRUDA
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	KEYTRUDA
D.3.4	Pharmaceutical form	Concentrate for concentrate for 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.3.9.4	EV Substance Code	AS2
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Recurrent/metastatic head and neck squamous cell cancer

E.1.1.1

Medical condition in easily understood language

Cancer of the head & neck that has come back or spread to other parts of the body

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	10067821
E.1.2	Term	Head and neck cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10060121
E.1.2	Term	Squamous cell carcinoma of head and neck
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

The main question we want to answer is whether giving pembrolizumab to patients with head and neck cancer that has come back, or spread to other parts of the body, can help to control the disease.

E.2.2

Secondary objectives of the trial

We will look at other measures of how effective the treatment is, such as in how many patients does the cancer shrink, how long does it take before the cancer starts to grow, and how long do the patients live. We will also look at
the side effects.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck that is considered incurable by local therapies.
2. Measurable disease evaluated by RECIST v1.1
3. WHO performance status of 2
4. Life expectancy of at least 12 weeks
5. Aged ≥ 18 years of age
6. Adequate bone marrow function:
- Absolute neutrophils ≥ 1.5 × 109/L
- Platelets ≥ 100 x 109/L
- Haemoglobin ≥ 90 g/L
7. Adequate renal function:
- Creatinine ≤ 1.5 x ULN
- Calculated glomerular filtration rate (GFR) ≥ 50 mL/min estimated using validated creatinine clearance calculation (e.g. Cockroft-Gault or Wright formula). 8. Adequate liver function:
- Serum bilirubin ≤ 1.5 x ULN
- AST and ALT ≤ 2.5 × ULN (≤ 5 x ULN for patients with liver metastases)
9. Willing to use highly effective contraception for the duration of trial treatment and for 120 days after completion of treatment
10. Willing to have a new biopsy, if site of disease is accessible and considered safe to biopsy by investigator
11. Able to give informed consent, indicating that the patient has been informed of and understands the experimental nature of the study, possible risks and benefits, trial procedures, and alternative options
12. Willing and able to comply with the protocol for the duration of the study, including the treatment plan, investigations required and follow up visits

E.4

Principal exclusion criteria

1. Patients with undifferentiated nasopharyngeal or sino-nasal cancers
2. Disease suitable for treatment with curative intent
3. Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent
4. Any investigational agents within 4 weeks prior to registration
5. Anti-cancer monoclonal antibody therapy within 4 weeks prior to registration
6. Chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to registration
7. Patients with concurrent or previous malignancy that could compromise assessment of the primary or secondary endpoints of the trial
8. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
9. Grade 3 or 4 peripheral neuropathy
10. Any serious and/or unstable pre-existing medical, psychiatric or other condition that, in the treating clinician’s judgment, could interfere with patient safety or obtaining informed consent
11. 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 for at least four weeks prior to the first dose of trial treatment
- Have no evidence of new or enlarging brain metastases
- Have no evidence of leptomeningeal disease
- Are not using steroids for at least 7 days prior to trial treatment
12. Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is detected)
- NB: Without known history, testing is required to determine eligibility. Hepatitis C antibody testing is allowed for screening purposes in sites where HCV RNA is not part of standard of care
13. Immunocompromised patients (e.g. known HIV positive status)*
14. Prior organ transplantation including allogenic stem-cell transplantation
15. Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
16. Active infection requiring systemic therapy
17. Has received a live vaccine within 30 days prior to registration (seasonal flu vaccines that do not contain live virus are permitted)
18. 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 (NB: the use of physiologic doses of corticosteroids may be approved after consultation with UCL CTC)
19. Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with the following are eligible:
- Autoimmune-related hyperthyroidism or autoimmune-related hypothyroidism who are in remission or on a stable dose of thyroid-replacement hormone
- Vitiligo
- Psoriasis
20. Current use of immunosuppressive medication, except for the following:
- intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
- Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

*Testing for HIV for the POPPY trial is not mandatory, however if this test has been done the result should be known prior to registration.

E.5 End points

E.5.1

Primary end point(s)

Disease control rate at 24 weeks (+/-28 days) after registration assessed using iRECIST

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks after registration

E.5.2

Secondary end point(s)

1. Disease control rate at 12 months, defined as a complete response, partial response or stable disease
2. Best Response Rate, measured using the change from baseline tumour size, assessed using iRECIST
3. Clinical benefit rate, defined as a complete response, partial response or stable disease, for ≥ 18 weeks from start of treatment
4. Duration of response
5. Time to progression (TTP)
6. Progression free survival (PFS)
7. Overall survival (OS)
8. Frequency and severity of adverse events, recorded continuously in relation to each treatment cycle and graded using CTCAE criteria
9. Treatment related dose delays or treatment discontinuation due to toxicity

E.5.2.1

Timepoint(s) of evaluation of this end point

1. 12 months after registration
2. 6 months after registration
3. every 8 weeks for 24 weeks, then every 9 weeks, from start of treatment
4. from first documented evidence of CR or PR until disease progression or death
5. from registration to the first documented disease progression
6. from registration to the first documented disease progression or death
7. from registration to death from any cause

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

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.8.3

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

For regulatory purposes the end of the trial will be 30 months after the final patient starts treatment, or death of all patients, whichever is sooner.

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