Clinical Trials Register

Summary
EudraCT Number:	2020-004426-36
Sponsor's Protocol Code Number:	MK-3475-B60
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-07
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-004426-36

A.3

Full title of the trial

A Phase II single-arm study of pembrolizumab plus lenvatinib in previously treated classic Kaposi sarcoma (CKS)

Studio clinico di fase II a singolo braccio di pembrolizumab in associazione a lenvatinib per i pazienti con sarcoma di Kaposi classico pretrattato

A.3.1

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

Clinical trial of combined therapy with pembrolizumab and lenvatinib for patients with classic Kaposi sarcoma treated with at least one previous line of chemioterapy.

Studio clinico della terapia combinazione di pembrolizumab e lenvatinib nei pazienti con sarcoma di Kaposi classico trattato con una precedente chemioterapia.

A.3.2

Name or abbreviated title of the trial where available

PULSAR

A.4.1

Sponsor's protocol code number

MK-3475-B60

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	FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
B.1.3.4	Country	Italy
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 Corp.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
B.5.2	Functional name of contact point	UOC Oncologia Medica
B.5.3	Address:
B.5.3.1	Street Address	Via Commenda, 19
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20122
B.5.3.4	Country	Italy
B.5.4	Telephone number	0255032666
B.5.5	Fax number	0255032659
B.5.6	E-mail	alice.indini@policlinico.mi.it

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	Lenvatinib
D.3.2	Product code	[E7080/MK7902]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lenvatinib Mesilato
D.3.9.1	CAS number	857890-39-2
D.3.9.2	Current sponsor code	Lenvatinib
D.3.9.3	Other descriptive name	Lenvatinib Mesylate
D.3.9.4	EV Substance Code	SUB72971
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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.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 (pembrolizumab, MK3475
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V. EU/1/15/1024/002
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.3.2	Product code	[Pembrolizumab]
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	MK3475
D.3.9.4	EV Substance Code	SUB167136
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 3
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	Lenvatinib
D.3.2	Product code	[E7080/MK7902]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lenvatinib Mesilato
D.3.9.1	CAS number	857890-39-2
D.3.9.2	Current sponsor code	Lenvatinib
D.3.9.3	Other descriptive name	Lenvatinib Mesylate
D.3.9.4	EV Substance Code	SUB72971
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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

Advanced unresectable classic Kaposi sarcoma relapsed and/or refractory to previous standard treatments.

Sarcoma di Kaposi classico stadio avanzato non resecabile, recidivato e/o refrattario a precedenti trattamenti standard.

E.1.1.1

Medical condition in easily understood language

Advanced unresectable classic Kaposi sarcoma, with progression and/or disease relapse during previous chemotherapy.

Sarcoma di Kaposi classico avanzato non operabile, che abbia mostrato una progressione e/o una recidiva a una precedente chemioterapia.

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10023284
E.1.2	Term	Kaposi's sarcoma
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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10023284
E.1.2	Term	Kaposi's sarcoma
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main objective of the study is to evaluate the response rate to the treatment with pembrolizumab and lenvatinib in patients with previously treated relapsed/refractory Kaposi sarcoma.

L’obiettivo principale dello studio è valutare il tasso di risposta al trattamento con pembrolizumab e lenvatinib nei pazienti con sarcoma di Kaposi recidivato o refrattario al trattamento standard.

E.2.2

Secondary objectives of the trial

The secondary objective of the study include the evaluation of the duration of response; evaluation of the impact of combination therapy on survival; treatment tolerability in this patients’ subgroup (including evaluation of the incidence of treatment related adverse events, and the impact of treatment on the patients’ quality of life).

Gli obiettivi secondari includono la valutazione della durata della risposta; la valutazione dell’impatto della terapia di combinazione sulla sopravvivenza; la tollerabilità al trattamento sperimentale in questo sottogruppo di pazienti (inclusi l’incidenza di eventi avversi correlati al trattamento, e l’impatto del trattamento sulla qualità della vita dei pazienti).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Histologic diagnosis of classic Kaposi sarcoma; progression, relapse or inadequate response to at least one prior systemic chemotherapy; presence of measurable disease by Positron Emission Tomography-Computed Tomography (PET-CT) scan and/or dermatological examination; at least 1 superficial lesion willing to provide tissue from cutaneous and/or mucosal biopsy at baseline; be = 18 years of age at the time of signing informed consent; have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 within 7 days before the first dose of study intervention; have adequate bone marrow, liver and renal function; have adequately controlled blood pressure.

Diagnosi istologica di sarcoma di Kaposi classico; progressione, recidiva o risposta inadeguata a =1 linea di trattamento standard; presenza di malattia misurabile agli esami strumentali (tomografia ad emissione di positroni, PET/TC) e/o all’esame dermatologico; possibilità di effettuare biopsia di una lesione cutanea e/o mucosa prima dell’avvio del trattamento; età =18 anni; performance status (PS) 0-1 secondo classificazione Eastern Cooperative Oncology Group (ECOG); adeguata funzionalità midollare, epatica e renale; adeguato controllo della pressione arteriosa.

E.4

Principal exclusion criteria

Has a known history of human immunodeficiency virus (HIV) infection, of active infectious hepatitis type B (hepatitis B surface antigen [HBsAg] detected) or C (hepatitis C virus [HCV] ribonucleic acid [RNA] detected) or active Tuberculosis Bacillus (TB); presence of known additional malignancy that is progressing or requires active treatment; has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); has had an allogeneic tissue/solid organ transplant; significant cardiovascular impairment within 12 months of the first dose of study intervention; history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption; previous immunotherapy with ICI(s).

Infezione da virus dell’immunodeficienza umana (HIV), infezione attiva da virus dell’epatite B (HBV) o dell’epatite C (HCV), o tubercolosi attiva; storia di neoplasia che richiede trattamento sistemico; malattia autoimmune attiva che ha richiesto trattamento con terapie sistemiche (es. corticosteroidi, immunosoppressori) nei 2 anni precedenti la valutazione per inclusione nello studio; pregressi trapianti allogenico e/o di organo solido; presenza di comorbidità cardiovascolare severa; malattia gastrointestinale che potrebbe compromettere l’assorbimento di farmaci per via orale; precedente trattamento con ICI.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study is to estimate the overall response rate (ORR) during treatment with pembrolizumab and lenvatinib in patients with previously treated relapsed/refractory classic Kaposi sarcoma.

L’endpoint primario dello studio è la stima del tasso di risposta globale (overall response rate, ORR) al trattamento con pembrolizumab e lenvatinib nei pazienti con sarcoma di Kaposi classico pre-trattato recidivato.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

6 mesi

E.5.2

Secondary end point(s)

To estimate the duration of response (DOR) in patients with pre-treated recurrent CKS receiving pembrolizumab with lenvatinib; to estimate the progression free survival (PFS); to estimate the overall survival (OS); to estimate the mean change from baseline in the global health status/quality of life (QoL), and physical functioning for the combinations of pembrolizumab and lenvatinib; to estimate the safety and tolerability for the combination of pembrolizumab and lenvatinib; to evaluate changes in plasma levels of HHV8 DNA at baseline and at the time of treatment discontinuation, due to any cause (i.e. disease progression, complete response, unacceptable treatment related toxicity); to evaluate changes in plasma levels of circulating markers (i.e. PD-1/PD-L1, VEGF, VEGF-R) at baseline and at the time of treatment discontinuation, due to any cause (i.e. disease progression, complete response, unacceptable treatment related toxicity); to analyze PD-L1 and VEGF expression, and tumor infiltrating lymphocytes in tumor specimens at baseline and at the time of disease progression (optional).

Stima della durata della risposta (duration of response, DOR); stima della sopravvivenza libera da progressione (progression free survival, PFS); stima della sopravvivenza globale (overall survival, OS); stima di eventuali variazioni nello status di salute globale/qualità di vita in corso di trattamento; stima della sicurezza e tollerabilità del trattamento di combinazione; valutazione delle variazioni nei livelli di HHV-8 DNA in corso di trattamento; valutazione delle variazioni di biomarcatori circolanti (PD-1/PD-L1, VEGF, VEGF-R); analisi dell’espressione di PD-L1 e VEGF sul tessuto tumorale prima dell’inizio del trattamento e al momento della progressione di malattia (opzionale).

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months

6 mesi

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

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability; quality of life

Tollerabilità; qualità della vita.

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Information not present in EudraCT

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.1.1.1

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)

All participants will be followed for overall survival and late-onset adverse events until death, withdrawal of consent, lost to follow-up, or the end of the study. The end of the study will be when the last participant completes the last study-related telephone call or visit, withdraws from the study, or is lost to follow-up (ie, the participant is unable to be contacted by the investigator).

Tutti i partecipanti saranno seguiti per la sopravvivenza complessiva e gli eventi avversi tardivi fino alla morte, al ritiro del consenso, alla perdita del follow-up o alla fine dello studio. La fine dello studio avverrà quando l'ultimo partecipante completerà l'ultima telefonata o visita relativa allo studio, si ritirerà dallo studio, o sarà perso per il follow-up (cioè, il partecipante non potrà essere contattato dal ricercatore).

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

2021-05-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-03-02

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials