Clinical Trials Register

Summary
EudraCT Number:	2020-005609-20
Sponsor's Protocol Code Number:	MK3475-B68
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-03-19
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

Czechia - SUKL

A.2

EudraCT number

2020-005609-20

A.3

Full title of the trial

A Phase 2 Study of Pembrolizumab (MK-3475) every 6 weeks (Q6W) in
Participants with Relapsed or Refractory Classical Hodgkin’s Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)

Klinické hodnocení fáze 2 s přípravkem pembrolizumab (MK-3475) podávaným jednou za 6 týdnů pacientům s relabujícím nebo refrakterním klasickým Hodgkinovým lymfomem (rrcHL) a relabujícím nebo refrakterním primárním mediastinálním velkobuněčným B-lymfomem (rrPMBCL)

A.3.1

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

Study of Pembroliumab Given Every Six Weeks to Participants with rrcHL or rrPMBCL

Klinické hodnocení fáze 2 zkoumající léčbu rrcHL nebo rrPMBCL přípravkem MK-3475 podávaným jednou za 6 týdnů

A.4.1

Sponsor's protocol code number

MK3475-B68

A.5.4

Other Identifiers

Name:

IND

Number:

118604

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 LLC
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 LLC
B.4.2	Country	Czechia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme LLC
B.5.2	Functional name of contact point	Katherine Ryland
B.5.3	Address:
B.5.3.1	Street Address	126 East Lincoln Avenue P.O. Box 2000
B.5.3.2	Town/ city	Rahway, NJ
B.5.3.3	Post code	07065
B.5.3.4	Country	United States
B.5.4	Telephone number	0019087406716
B.5.6	E-mail	katherine.ryland@merck.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	Yes
D.2.1.1.1	Trade name	KEYTRUDA® (Pembrolizumab, MK-3475)
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.3.2	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	SUB167136
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

Relapsed or refractory Classical Hodgkins Lymphoma and relapsed or refractory Primary Large B-cell Lymphoma

E.1.1.1

Medical condition in easily understood language

Relapsed or refractory Classical Hodgkins Lymphoma and relapsed or refractory Primary Large B-cell

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10080208
E.1.2	Term	Classical Hodgkin lymphoma
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	10012822
E.1.2	Term	Diffuse large B-cell lymphoma refractory
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	10012821
E.1.2	Term	Diffuse large B-cell lymphoma recurrent
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

1. To evaluate objective response rate (ORR), by cohort, relapsed or refractory classical Hodgkin’s Lymphoma (rrcHL) and relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL), as assessed by the investigator according to Lugano classification criteria [Cheson, B. D., et al 2014] in individuals treated with pembrolizumab every 6 weeks (Q6W).

E.2.2

Secondary objectives of the trial

1. To evaluate objective response rate (ORR), by cohort, rrcHL and rrPMBCL, as assessed by blinded independent central review (BICR) according to Lugano classification criteria [Cheson, B. D., et al 2014] in individuals treated with pembrolizumab Q6W.
2. To evaluate duration of response (DOR), by cohort, rrcHL and rrPMBCL, as assessed by the investigator according to Lugano classification criteria [Cheson, B. D., et al 2014] in individuals treated with pembrolizumab Q6W.
3. To evaluate duration of response (DOR), by cohort, rrcHL and rrPMBCL, as assessed by BICR according to Lugano classification criteria [Cheson, B. D., et al 2014] in individuals treated with pembrolizumab Q6W.
4. To evaluate the pharmacokinetic (PK) profile, immunogenicity of pembrolizumab 400 mg Q6W.
5. To evaluate the safety and tolerability of pembrolizumab Q6W.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male/female participants who are at least 18 years of age on the day of signing informed consent.
2. Have a histologically confirmed diagnosis of cHL or PMBCL, according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues [Swerdlow, S. H., et al 2008].
3. Have radiographically measurable cHL or PMBCL disease as per Lugano classification with at least 1 nodal lesion (which has not been previously radiated) that is >15 mm in long axis, regardless of the length of the short axis, and/or extranodal lesion of >10 mm in long and short axis.
4. Have relapsed or refractory PMBCL and:
Have relapsed after auto-SCT or have failed to achieve a CR or PR within 60 days of auto-SCT. Participants may have received intervening therapy after auto-SCT for relapsed or refractory disease, in which case they must have relapsed after or be refractory to their last treatment.
OR
For participants who are ineligible for auto-SCT, have received at least ≥2 lines of prior therapy and have failed to respond to or relapsed after their last line of treatment. At least 1 of the prior lines of therapy must contain a rituximab-based regimen. For participants who received consolidative local radiotherapy after systemic therapy, local radiotherapy will not be considered as a separate line of
treatment.
5. Have relapsed or refractory cHL and:
Have relapsed during their last cHL regimen after receiving at least 2 cycles of therapy or within 12 months after completing the last regimen for cHL.
OR
Have received at least ≥1 line of prior multiagent therapy with/without brentuximab vedotin (excluding radiation) or auto-SCT for cHL and have failed to respond to or relapsed after their last line of treatment.
6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
Is not a WOCBP
OR
Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 5 of the protocol during the intervention period and for at least 120 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention.
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Abstains from breastfeeding during the study intervention period and for at least 120
days after study intervention.
Additional requirements for pregnancy testing during and after study intervention are located in the protocol
The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
7. The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. The participant may also provide consent/assent for FBR.
However, the participant may participate in the study without participating in FBR.
8. Submit an evaluable core lymph node biopsy for biomarker analysis from an archival (>60 days) or newly obtained core or incisional (within 30 days) biopsy, which was not previously irradiated at Screening (Visit 1).
9. Have an ECOG Performance Status of 0 to 1 assessed within 7 days before allocation.
10. Life expectancy >3 months.
11. Have blood oxygen saturation >92%.
12. Have adequate organ function as defined in the protocol. Specimens must be collected within 7 days before the start of study intervention.

E.4

Principal exclusion criteria

1. Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic SCT within the last 5 years. Participants who have had allogeneic hematopoietic SCT >5 years ago are eligible as long as there are no symptoms of GVHD.
2. Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication.
3. Has pericardial effusion or clinically significant pleural effusion.
4. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
5. Is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) <3 days prior to the first dose of study intervention.
6. Has received prior monoclonal antibody within 4 weeks prior to first dose of study intervention or has not recovered (ie, ≤Grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier.
7. 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 coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
8. Has received prior CAR-T therapy.
9. Has received prior systemic anticancer therapy, or radiotherapy, including investigational agents within 4 weeks prior to the first dose of study intervention.
10. Has received prior radiotherapy within 2 weeks of start of study intervention or have had
a history of radiation pneumonitis.
11. Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug.
12. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
13. Has a diagnosis of immunodeficiency or is receiving chronic 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 study medication.
14. Has known active CNS lymphoma involvement or active CNS involvement by lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease) and clinical remission.
15. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
16. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, 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.
17. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
18. Has an active infection requiring systemic therapy.
19. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority.
20. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
21. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
22. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.

E.5 End points

E.5.1

Primary end point(s)

1. Objective Response Rate (ORR) per Lugano Classification as Assessed by Investigator

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Up to approximately 40 months

E.5.2

Secondary end point(s)

1. ORR per Lugano Classification as Assessed by blinded independent central review (BICR)
2. Duration of Response (DOR) per Lugano Classification as Assessed by Investigator
3. DOR per Lugano Classification as Assessed by BICR
4. Area Under the Curve (AUC) of Pembrolizumab
5. Maximum Serum Concentration (Cmax) of Pembrolizumab
6. Minimum Serum Concentration (Cmin) of Pembrolizumab
7. Antidrug Antibody Levels for Pembrolizumab
8. Number of Participants Who Experienced an Adverse Events (AEs)
9. Number of Participants Who Discontinued Study Treatment Due to an AE

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Up to appr. 40 months
2. Up to appr. 40 months
3. Up to appr. 40 months
4. Predose 0-4 hours on Cycle 1, Day 1 (C1D1), C2D1, C4D1, C5D1, C7D1, C9D1, C13D1 & C17D1 & end of infusion on C1D1 & C4D1, & anytime on C1D22 & C4D22 (cycle length=6 weeks)
5. Predose 0-4 hours on C1D1, C2D1, C4D1, C5D1, C7D1, C9D1, C13D1 & C17D1 & end of infusion on C1D1 & C4D1, & anytime on C1D22 & C4D22 (cycle length=6 weeks)
6. Predose 0-4 hours on C1D1, C2D1, C4D1, C5D1, C7D1, C9D1, C13D1 & C17D1 & end of infusion on C1D1 & C4D1, & anytime on C1D22 & C4D22 (cycle length=6 weeks)
7. Predose 0-4 hours on C1D1, C2D1, C4D1, C5D1, C7D1, C9D1, C13D1 & C17D1 & end of infusion on C1D1 & C4D1, & anytime on C1D22 & C4D22 (cycle length=6 weeks)
8. Up to appr. 30 months
9. Up to appr. 27 months

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

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

Yes

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

Colombia

New Zealand

Switzerland

Ukraine

Australia

Brazil

Canada

Czechia

France

Italy

Poland

Romania

Russian Federation

South Africa

Turkey

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

The overall study ends when the last participant completes the last study-related contact, withdraws consent, or is lost to follow-up. For purposes of analysis and reporting, the overall study ends when the Sponsor receives the last laboratory result or at the time of final contact with the last participant, whichever comes last.

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-05-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-12

P. End of Trial
P.	End of Trial Status	Ongoing

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