Clinical Trials Register

Summary
EudraCT Number:	2017-002841-31
Sponsor's Protocol Code Number:	PEOPLE
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:	2021-06-15
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-002841-31

A.3

Full title of the trial

Phase II study to test Pembrolizumab (MK-3475) in first line treatment of advanced NSCLC patients with PD-L1 low tumors (<50%)_ PEOPLE TRIAL (Pembrolizumab in Pd-L1 low Expressors)

Studio di Fase II (PEOPLE PEmbrOlizumab in mild Pd-L1 Expressors) per valutare Pembrolizumab (MK-3475) come trattamento di prima linea, in pazienti con tumore al polmone non a piccole cellule in stadio avanzato con espressione bassa o moderata di PD-L1 (< 50%).

A.3.1

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

Phase II study to test Pembrolizumab (MK-3475) in first line treatment of advanced NSCLC patients with PD-L1 low tumors (<50%)_ PEOPLE TRIAL (Pembrolizumab in Pd-L1 low Expressors)

A.3.2

Name or abbreviated title of the trial where available

PEOPLE

A.4.1

Sponsor's protocol code number

PEOPLE

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN00000000

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00000000

A.5.3

WHO Universal Trial Reference Number (UTRN)

U0000-0000-0000

A.5.4

Other Identifiers

Name:

PEOPLE

Number:

PEOPLE

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 "ISTITUTO NAZIONALE DEI TUMORI"
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 Istituto Nazionale Tumori
B.5.2	Functional name of contact point	Clinical Trial Center
B.5.3	Address:
B.5.3.1	Street Address	Via G.Venezian,1
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20133
B.5.3.4	Country	Italy
B.5.4	Telephone number	0223903836
B.5.5	Fax number	0223903991
B.5.6	E-mail	trialcenter@istitutotumori.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	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	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	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.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 NSCLC patients with PD-L1 low tumors (<50%)

Tumore al polmone non a piccole cellule in stadio avanzato con espressione bassa o moderata di PD-L1 (< 50%).

E.1.1.1

Medical condition in easily understood language

Non-Small Cell Lung Cancer

Tumore al Polmone non a piccole cellule

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	10059515
E.1.2	Term	Non-small cell lung cancer metastatic
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

To identify immune biomarkers associated with Progression-free-survival (PFS).

Identificazione di potenziali biomarcatori associati alla sopravvivenza libera da progressione (PFS).

E.2.2

Secondary objectives of the trial

-To detect differences in immune biomarkers distribution between pre and post Pembrolizumab treatment;
- Objective Response Rate (ORR);
- Response Duration (DoR);
-Disease Control Rate (DCR);
- Overall Survival (OS);
- To estimate the safety of Pembrolizumab treatment;
- To estimate patient¿reported health status for physical, mental, and social well¿being.

-Identificazione di potenziali differenze nell¿espressione di biomarcatori immunitari tra campioni ottenuti prima e dopo il trattamento con Pembrolizumab;
-Tasso complessivo di risposta (ORR);
-Durata di risposta (DOR);
-Tasso di controllo di malattia (DCR);
-Sopravvivenza globale (OS);
-Stima della sicurezza di Pembrolizumab monitorando gli eventi avversi;
-Stato di salute globale riportato dai pazienti

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Have a confirmed diagnosis of NSCLC in stage IIIB/ IV. Do not have an EGFR sensitizing (activating) mutation or ALK translocation and have a PD-L1 “low” (<50%) tumor as determined by immunohistochemistry with anti-PD-L1 antibody (DAKO 22C3). Have not received prior systemic chemotherapy treatment for advanced NSCLC.
2. Be willing and able to provide written informed consent/assent for the trial.
3. Be = 18 years of age on day of signing informed consent.
4. Have measurable disease based on RECIST 1.1.
5. Be willing to provide tissue from archived histological specimen or newly obtained core or excisional biopsy of a tumor lesion.
6. Have a performance status of 0 or 1 on the ECOG Performance Scale.
7. Demonstrate adequate organ function.All screening labs should be performed within 10 days of treatment initiation.
8.Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication.
9. 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
10. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
11. No history of active malignancy requiring treatment.

1.Diagnosi istologica di NSCLC in stadio IIIB/IV, senza mutazioni attivanti di EGFR né traslocazione di ALK, con espressione IHC (anticorpo DAKO 22C3) di PD-L1<50% , mai trattati in precedenza con alcuna terapia sistemica per la malattia avanzata.
2. Consenso informato firmato e datato.
3. Età =18 anni al momento della firma del consenso informato.
4. Presenza di malattia misurabile in base ai criteri RECIST V. 1.1.
5. Disponibilità di tessuto da materiale d’archivio o da biopsia di una lesione tumorale,.
6. Performance status 0 o 1 secondo la scala ECOG.
7.Adeguata funzionalità midollare, epatica e renale agli esami di laboratorio di screening, effettuati entro 10 giorni dall’avvio del trattamento sperimentale.
8. Per le pazienti di sesso femminile in età fertile, negatività del test di gravidanza su urine o su siero entro 72 ore dall’avvio del trattamento sperimentale.
9. Per le pazienti di sesso femminile in età fertile, disponibilità all’utilizzo di 2 metodi contraccettivi o all’astensione completa dall’attività sessuale per tutta la durata della partecipazione allo studio e fino a 120 giorni dopo l’ultima somministrazione del farmaco sperimentale.
10. Per i pazienti di sesso maschile, disponibilità all’uso di adeguati metodi contraccettivi per tutta la durata della partecipazione allo studio e fino a 120 giorni dopo l’ultima somministrazione del farmaco sperimentale.
11. Anamnesi personale negativa per neoplasie maligne.

E.4

Principal exclusion criteria

The subject must be excluded from participating in the trial if the subject:
1. Has an EGFR sensitizing mutation and/or an ALK translocation.
2. Has a PD-L1 expression assessed as "high" by the central laboratory
3. 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.
4. Has a known history of active TB (Bacillus Tuberculosis).
5. Hypersensitivity to Pembrolizumab or any of its excipients.
6. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
7. 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 are an exception to this criterion and may qualify for the study.
8. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
9. 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). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
10. Has a history of non-infectious pneumonitis that required steroids or has current pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. 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.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
18. Has received a live vaccine within 30 days of planned start of study therapy.

1.Presenza di mutazione sensibilizzante di EGFR e/o di traslocazione di ALK sul tessuto tumorale.
2. Alta espressione di PD-L1 all’analisi IHC centralizzata (>50%).
3. Diagnosi d’immunodeficienza o assunzione di terapia steroidea/immunosoppressiva sistemica entro 7 giorni dalla prima somministrazione del trattamento sperimentale.
4. Anamnesi personale di tubercolosi attiva.
5. Ipersensibilità nota a Pembrolizumab o a uno dei suoi eccipienti.
6. Trattamento anti-neoplastico con anticorpo monoclonale entro 4 settimane dall’avvio del trattamento sperimentale o mancata risoluzione di eventi avversi legati a terapie somministrate prima di questa data (a eccezione di neuropatia di grado =2 e di chirurgia maggiore seguita da recupero adeguato).
7. Terapia citotossica, a bersaglio molecolare o radiante somministrata entro 2 settimane dall’avvio del trattamento sperimentale.
8. Seconda neoplasia in progressione o necessitante trattamento attivo (a eccezione del carcinoma basocellulare della cute e del carcinoma in situ della cervice uterine potenzialmente suscettibili di terapia locale curativa).
9. Anamnesi personale di malattia autoimmune necessitante terapia sistemica con steroidi o immunomodulanti nei precedenti 2 anni (la terapia ormonale sostitutiva, es. con tiroxina o insulina, non è considerata una forma di terapia sistemica).
10. Anamnesi personale di polmonite non infettiva necessitante di terapia steroidea o polmonite in atto.
11. Infezione attiva necessitante terapia sistemica.
12. Anamnesi personale o evidenza attuale di qualunque condizione, terapia o anomalia di laboratorio potenzialmente confondente i risultati dello studio, interferente con la partecipazione del paziente allo stesso o suggestiva all’opinione dello sperimentatore che lo studio non costituisca per il paziente l’opzione terapeutica migliore.
13. Patologia psichiatrica potenzialmente interferente con la partecipazione del paziente allo studio o abuso di sostanze.
14. Gravidanza o allattamento, ovvero desiderio di concepimento durante la prevista durata dello studio, a partire dall’avvio del pre-screening e fino a 120 giorni dopo l’ultima somministrazione di farmaco sperimentale.
15. Pregressa terapia con agenti anti-PD1, anti-PD-L1 o anti-PD-L2.
16. Anamnesi personale d’infezione da HIV (positività anticorpale per HIV1 o HIV2).
17. Epatite B o C attiva (es. positività per HBsAg, riscontro di HCV RNA circolante).
18. Somministrazione di vaccini vivi entro 30 giorni dalla data prevista di avvio della terapia sperimentale (il vaccino per l’influenza stagionale a base di virus inattivato è consentito, ma non quello intranasale a base di virus vivo attenuato).

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS)

Sopravvivenza libera da progressione (PFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Progression-free-survival is defined as the time from enrolement to the first documented disease progression per RECIST 1.1 based on radiologists’ review or death due to any cause, whichever occurs first.

Sopravvivenza libera da progressione( PFS) è definita come l’intervallo di tempo tra l’arruolamento del paziente nello studio e la prima progressione di malattia secondo RECIST 1.1 o la morte.

E.5.2

Secondary end point(s)

Overall Survival (OS); Response Duration (DoR); Overall Response Rate (ORR); Disease Control Rate (DCR)

Sopravvivenza globale (OS); Durata della risposta ( DoR); Tasso complessivo di risposta (ORR); Tasso di controllo di malattia (DCR)

E.5.2.1

Timepoint(s) of evaluation of this end point

Overall Survival (OS) is defined as the time from errollement 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.; The Duration of Response (DoR) is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.; Overall response rate (ORR) is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). It will be evaluated throughout the entire duration of the study.; The Disease Control Rate (DCR) is defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, par

Sopravvivenza globale (OS), definita come l¿intervallo di tempo tra l¿arruolamento del paziente nello studio e la morte per qualunque causa.; La durata di risposta (DOR) ¿ definita come l¿intervallo di tempo fra la data di riscontro di risposta completa o parziale e la data di progressione di malattia nei pazienti ottenenti documentato beneficio dalla terapia sperimentale; Il tasso complessivo di risposta (ORR) ¿ definito come la proporzione di pazienti con risposta completa o parziale alla terapia sperimentale. Sar¿ valutato sull'intera durata dello studio.; Il tasso di controllo di malattia (DCR) ¿ definito come la somma delle percentuali di pazienti ottenenti risposta completa, risposta parziale e stabilizzazione di malattia. Sar¿ valutato sull'intera durata dello studio.

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

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

Yes

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

Yes

E.8.2.3.1

Comparator description

nessun comparatore

none comparator

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)

Follow-up

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

2018-01-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-10-25

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

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