Clinical Trials Register

Summary
EudraCT Number:	2019-001757-54
Sponsor's Protocol Code Number:	APL-101-01
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-001757-54

A.3

Full title of the trial

Phase 1 / 2 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects with Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors

Studio multicentrico di fase 1/2 per valutare la sicurezza, la farmacocinetica e l’efficacia preliminare di APL-101 in soggetti con carcinoma polmonare non a piccole cellule con mutazioni di c-Met associate a salto dell’ESONE 14 e tumori solidi in stadio avanzato con disregolazione di c-Met

A.3.1

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

APL-101 is a novel small molecule agent that is a “kinase inhibitor”, which binds to the c-Met protein and disrupts the c-Met pathway that should cause cell death in tumor cells overexpressing c-Met protein.
The c-Met is a protein that is frequently changed in cancers. Cancer cells often use c-Met activation to stimulate cell growth and escape therapies; therefore, the c-Met pathway is considered to be an important target for cancer therapies.

APL-101 è una piccola molecola con azione di "inibitore della chinasi", si lega alla proteina c-Met e interrompe l'azione di c-Met, causando la morte delle cellule tumorali che sovraesprimono la proteina c-Met.
Il c-Met è una proteina che viene frequentemente modificata nei tumori. Le cellule tumorali usano spesso l'attivazione di c-Met per stimolare la crescita cellulare e sfuggire alle terapie; pertanto c-Met è considerato un obiettivo importante per le terapie del cancro.

A.3.2

Name or abbreviated title of the trial where available

SPARTA

A.4.1

Sponsor's protocol code number

APL-101-01

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03175224

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	Apollomics 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	Apollomics, 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	Medpace
B.5.2	Functional name of contact point	Clinical Trial Management
B.5.3	Address:
B.5.3.1	Street Address	5375 Medpace way
B.5.3.2	Town/ city	Cincinnati
B.5.3.3	Post code	45227
B.5.3.4	Country	United States
B.5.4	Telephone number	001513579991112160
B.5.6	E-mail	e.lefkovitz@medpace.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	APL-101
D.3.2	Product code	[APL-101]
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	CBT-101 Bozitinib
D.3.9.1	CAS number	1440964-89-5
D.3.9.2	Current sponsor code	APL-101
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	100
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

Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors

Carcinoma polmonare non a piccole cellule con mutazioni di c-Met associate a salto dell’ESONE 14 e tumori solidi in stadio avanzato con disregolazione di c-Met

E.1.1.1

Medical condition in easily understood language

A solid tumor carrying c-Met dysregulated genetic alterations or Non-Small Cell Lung Cancer (NSCLC) carrying MET EXON 14 skip mutations

Tumori solidi con disregolazione di c-Met o carcinoma polmonare non a piccole cellule (NSCLC) con mutazioni di c-Met associate a salto dell’ESONE 14

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	LLT
E.1.2	Classification code	10065252
E.1.2	Term	Solid tumor
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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10061873
E.1.2	Term	Non-small cell lung cancer
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

Phase 1 Primary Objective:
•To assess overall safety and tolerability, determine the dose limiting toxicities (DLTs), and identify the recommended Phase 2 dose (RP2D).

Phase 2 Primary Objective:
•To assess efficacy by overall response rate (ORR) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. or relevant evaluation criteria per tumor type.

Obiettivo primario della fase 1
• Valutare la sicurezza e la tollerabilità complessive, determinare le tossicità limitanti la dose (DLT), e individuare la dose raccomandata per la fase 2 (RP2D).

Obiettivo primario della fase 2
• Valutare l’efficacia in base al tasso di risposta complessiva (ORR) e alla durata della risposta (DOR) secondo i Criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1 o i criteri di valutazione rilevanti per tipo di tumore.

E.2.2

Secondary objectives of the trial

Phase 1/2 Secondary Objectives:
•To assess incidence of serious adverse events (SAEs) and adverse events (AEs) by relationship and severity grade.
•To determine the pharmacokinetic (PK) parameters of orally administered APL-101.
•To assess efficacy by clinical benefit rate (CBR: CR + PR + SD = 4 cycles), time to progression (TTP), progression free survival (PFS), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (or relevant evaluation criteria per tumor type) and overall survival (OS).

Obiettivi secondari della fase 1/2
• Valutare l’incidenza degli eventi avversi seri (SAE) e degli eventi avversi (EA) in base al rapporto e al livello di gravità.
• Determinare i parametri farmacocinetici (PK) di APL-101 somministrato per via orale.
• Valutare l’efficacia in base a tasso di beneficio clinico (CBR: CR + PR + SD = 4 cicli), tempo alla progressione (TTP), sopravvivenza libera da progressione (PFS), secondo i Criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1 (o i criteri di valutazione rilevanti per tipo di tumore), e sopravvivenza complessiva (OS).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Men/women = 18 years of age or older able to understand and signICF before study.
2. For Ph 1, histologically and/or cytological confirmed unresectable or metastatic solid malignancy, refractory to standard therapies with no more than three prior lines of therapy.
3.For Ph 2, five cohorts will be enrolled:
- 3a. Cohort A-1: EXON 14 NSCL Cancer – c-Met inhibitor naïve (1L)
- 3b. Cohort A-2: EXON 14 NSCL Cancer – c-Met inhibitor naïve (>2L)
- 3c. Cohort B: EXON 14 NSCL Cancer – c-Met inhibitor experienced
- 3d. Cohort C: Basket Tumor Types (c-Met high-level amplifications)
- 3e. Cohort D: Basket Tumor Types (c-Met fusions)
4.Abnormal c-Met dysregulation, by tissue and/or plasma, defined as the following from local/archival molecular pre-screening evaluations.
Phase 1 (100, 200, and 300 mg Cohorts)
a. c-Met overexpression by IHC 2+ = 50% of tumor cells
b. or c-Met amplification (c-Met/Cep-7 ratio = 2.2 or GCN = 6 gene copy)
c. or c-Met EXON 14 skip mutation per NGS or RT-PCR
d. or c-Met fusions including the following, but not limited to this list (LIST): BAIAP2L1; C8orf34; CAPZA2; DCTN1; EPS15; LRRFIP1; MET; OXR1; PPFIBP1; PTPRZ1; TFG; TPR; TRIM4; ZKSCAN1; KIF5B and any other known c-Met activating mutations
Phase 1 (400 mg Cohort) and Phase 2 RP2D
a.c-Met high-level amplification (c-Met/Cep-7 ratio of = 2.2 or GCN of = 6 copy). A minimum of five subjects of the high-level amplification (c- Met/Cep-7 ratio of = 5 or GCN = 10 gene copy) for the Stage 1 of the Simon 2 stage design is required)
b.or c-Met EXON 14 skip mutation per NGS
c.or c-Met fusions including the following, but not limited to the LIST
d. or other c-Met mutations in Dose Escalation (400 mg Cohort)
5. Local/archival result of a positive c-Met dysregulation is required. In Ph 2, Cohorts A and D require provision of tumor tissue samples. For Cohorts B and C, provision of tumor tissue or plasma sample for entry is acceptable.
6. Across Ph 2 five cohorts, treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is allowed.
7. Measurable disease according to RECIST v1.1. (or relevant criteria per tumor type).
8. ECOG performance status of 0–1.
9. Acceptable organ function, as evidenced by the following laboratory data during Screening period:
a.AST and alanine aminotransferase (ALT) = 2.5 x ULN
b.Total serum bilirubin = 1.5 x ULN
c.For subjects with liver metastases: Total bilirubin = 3.0 x ULN, AST/ALT = 5 x ULN
d.Absolute neutrophil count (ANC) = 1500 cells/mm3 (1.5 x 109/L)
e.Platelet count = 100,000 cells/mm3 (100 x 109/L)
f.Serum creatinine levels = 1.5 ULN or MDRD = 60 mL/min (CKD EPI
Creatinine Equation)
g.Hemoglobin = 9 g/dL
10.No chemotherapy treatments within at least 3 weeks prior to first dose of study treatment.
11.Adequate cardiac function or normal cardiac function with left ventricular ejection fraction (LVEF) =50% at screening.

1. Uomini e donne di età pari o superiore a 18 anni.
2. Per la fase 1, tumore maligno solido non resecabile o metastatico confermato a livello istologico e/o citologico, refrattario alle terapie standard con non più di tre precedenti linee di terapia.
3. Per la fase 2, saranno arruolate cinque coorti:
- 3a. Coorte A-1: NSCLC con mutazione associata a salto dell’ESONE 14 - naïve al trattamento con inibitori di c-Met (1L)
- 3b. Coorte A-2: NSCLC con mutazione associata a salto dell’ESONE 14 - naïve al trattamento con inibitori di c-Met (>2L)
- 3c. Coorte B: NSCLC con mutazione associata a salto dell’ESONE 14 - precedentemente trattati con inibitori di c-Met
- 3d. Coorte C: molteplici tipi di tumore (con alto livello di amplificazione di c-Met)
- 3e. Coorte D: molteplici tipi di tumore (con fusioni di c-Met)
4. Disregolazione anomala di c-Met, per tessuto e/o plasma, definita come segue dalle valutazioni di pre-screening molecolare su campioni locali/archiviati.
Fase 1 (coorti da 100, 200 e 300 mg)
a. sovraespressione di c-Met con risultato al test IHC pari a 2+ =50% delle cellule tumorali
b. o amplificazione di c-Met (rapporto c-Met/Cep-7 =2,2 o GCN =6)
c. o mutazione di c-Met associata a salto dell’ESONE 14 osservata mediante sequenziamento di nuova generazione (NGS) o reazione a catena della polimerasi in tempo reale (RT-PCR)
d. o fusioni di c-Met, comprese, a titolo non esaustivo, le seguenti nella lista (LISTA): AIAP2L1; C8orf34; CAPZA2; DCTN1; EPS15; LRRFIP1; MET; OXR1; PPFIBP1; PTPRZ1; TFG; TPR; TRIM4; ZKSCAN1; KIF5B e qualsiasi altra mutazione attivante di c-Met nota
Fase 1 (coorte da 400 mg) e RP2D di fase 2
a. alto livello di amplificazione di c-Met (rapporto c-Met/Cep-7 =2,2 o GCN =6). È necessario un minimo di cinque soggetti per l’amplificazione ad alto livello (rapporto c-Met/Cep-7 =5 o GCN =10) per la Parte 1 del disegno a 2 parti di Simon
b. o mutazione di c-Met con salto dell’ESONE 14 osservata mediante NGS
c. o fusioni di c-Met, comprese, a titolo non esaustivo, elencate nella LISTA
d. o altre mutazioni di c-Met nell’incremento della dose (Coorte da 400 mg)
5. È necessario un risultato locale/d’archivio di una disregolazione positiva di c-Met. Nella fase 2, le Coorti A e D richiedono la fornitura di tessuto tumorale (da campione archiviato o biopsia di tessuto tumorale fresco). Per le Coorti B e C, per l’ingresso è accettabile la fornitura di un campione di tessuto tumorale (da campione archiviato o biopsia di tessuto tumorale fresco) e/o plasma.
6. Nelle cinque coorti di fase 2, è consentita la malattia asintomatica del parenchima del SNC o la malattia leptomeningea, trattata o non trattata.
7. Malattia misurabile secondo i criteri RECIST v1.1 (o i criteri rilevanti per tipo di tumore).
8. Stato della performance pari a 0-1 del Gruppo cooperativo orientale di oncologia (ECOG).
9. Funzione d’organo accettabile, come evidenziato dai seguenti dati di laboratorio durante il periodo di screening:
a. Aspartato aminotransferasi (AST) e alanina aminotransferasi (ALT) = 2,5 x livello superiore dell’intervallo di normalità (ULN)
b. Bilirubina sierica totale =1,5 x ULN
c. Per i soggetti con metastasi epatiche: Bilirubina totale =3,0 x ULN, AST/ALT =5 x ULN
d. Conta assoluta dei neutrofili (ANC) =1500 cellule/mm3 (1,5 x 109/l)
e. Conta piastrinica =100.000 cellule/mm3 (100 x 109/l)
f. Livelli di creatinina sierica =1,5 ULN oppure MDRD =60 ml/min (equazione CKD EPI per il calcolo della creatinina)
g. Emoglobina =9 g/dl
10. Nessun trattamento chemioterapico almeno entro le 3 settimane precedenti alla prima dose di trattamento dello studio.
11. Funzione cardiaca adeguata o normale funzione cardiaca con frazione di eiezione ventricolare sinistra (LVEF) =50% allo screening.

E.4

Principal exclusion criteria

1.Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.
2.Known mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1, RET, NTRK, KRAS and BRAF.
3.Use or intended use of any other investigational product, including herbal medication through Study Treatment Termination.
4.Active uncontrolled systemic bacterial, viral, or fungal infection or clinically significant, active disease process, which in the opinion of the investigator makes the risk:benefit unfavorable for the participation of the trial. Screening for chronic conditions is not required.
5.Life-threatening illness, significant organ system dysfunction or comorbid conditions, or other reasons that, in the investigator's opinion, could compromise the subject's safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of APL-101.
6.History of, or currently, or at risk for, cardiac disease (e.g., long QT syndrome [> 450 msec QTcF or concurrent treatment with any medication that prolongs QT interval). 7.History of human immunodeficiency virus (HIV), or historical seropositive results consistent with active infection for hepatitis C virus (HCV) or hepatitis B virus (HBV) with high viral loads not actively managed with antiviral therapy. If history is unclear, a test at Screening will be required.
8.Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments.
9.Unable to swallow orally administered medication whole.
10.Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
11.Women who are breastfeeding.
12.Subjects with complications from prior radiation therapy will not be eligible until AEs return to baseline or = Grade 1.
13.Pregnant or breastfeeding woman.

1. Ipersensibilità ad APL-101, eccipienti del prodotto farmaceutico o altri componenti del regime di trattamento dello studio.
2. Nota mutazione/riarrangiamento genico di EGFR (eccetto per la Coorte C), ALK, ROS1, RET, NTRK, KRAS e BRAF.
3. Uso o uso previsto di qualsiasi altro prodotto sperimentale, anche medicinali a base di erbe, fino alla conclusione del trattamento dello studio.
4. Infezione sistemica attiva non controllata di natura batterica, virale o micotica o processo patologico attivo, clinicamente significativo che, secondo l’opinione dello sperimentatore, rende sfavorevole il rapporto rischio-beneficio per la partecipazione alla sperimentazione. Non è richiesto lo screening delle condizioni croniche.
5. Malattia potenzialmente letale, disfunzione del sistema d’organo significativa o condizioni di comorbilità, o altri motivi che, a giudizio dello sperimentatore, potrebbero compromettere la sicurezza del soggetto o l’integrità degli esiti dello studio, oppure interferire con l’assorbimento o il metabolismo di APL-101.
6. Anamnesi o attuale rischio di malattia cardiaca (ad es. sindrome del QT lungo [intervallo QT corretto con la formula di Fridericia (QTcF) >450 msec o trattamento concomitante con qualsiasi farmaco che prolunga l’intervallo QT).
7. Anamnesi del virus dell’immunodeficienza umana (HIV) o anamnesi di sieropositività coerenti con infezione attiva da virus dell’epatite C (HCV) o virus dell’epatite B (HBV), con carichi virali elevati non attivamente gestiti con terapia antivirale. Se la storia medica non è chiara, sarà necessario un test allo screening.
8. Nota malattia mentale significativa o altre condizioni quali abuso attivo di alcol o altre sostanze che, a giudizio dello sperimentatore, predispongono il soggetto ad un alto rischio di mancata aderenza al trattamento o alle valutazioni del protocollo.
9. Impossibilità di deglutire l’intero farmaco somministrato per via orale.
10. Compromissione della funzione gastrointestinale o malattia gastrointestinale che potrebbe interferire in modo significativo con l’assorbimento del farmaco (ad es. morbo di Crohn, colite ulcerosa, malattia infiammatoria intestinale attiva, nausea incontrollata, vomito, diarrea o sindrome da malassorbimento).
11. Donne che allattano.
12. I soggetti con complicanze derivanti da precedente radioterapia non saranno idonei finché gli EA non torneranno al livello basale o a un Grado =1.

E.5 End points

E.5.1

Primary end point(s)

Phase 1 Primary Endpoint
• Estimate the maximum tolerated dose (MTD) and the incidence of DLTs in Cycle 1, sustained Grade 2 adverse events, dose reductions, dose interruptions and any occurrences of delayed toxicities and other AEs to determine the RP2D dosing of APL-101.
Phase 2 Primary Endpoint
• Objective response rate (ORR = CR + PR) and median duration of response (DOR) per investigator assessment based on RECIST v1.1. (or relevant criteria per tumor type).

Obiettivo primario della fase 1
• Valutare la dose massima tollerata (MTD) e l'incidenza di DLTs nel Ciclo 1, eventi avversi di Grado 2 sostenuti, riduzioni della dose, interruzioni della dose and qualsiasi occorrenza di tossicità ritardata e altri AEs per determinare la dose RP2D di APL-101.

Obiettivo primario della fase 2
• Tasso di risposta obiettiva (ORR = CR + PR) e durata mediana della risposta (DOR) per valutazione dello sperimentatore basata su RECIST v1.1. (o criteri pertinenti per tipo di tumore).

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoints are described within the text in section E.5.1

I punti temporali sono descritti all'interno del testo nella sezione E.5.1

E.5.2

Secondary end point(s)

Phase 1/2 Secondary Endpoint(s)
• Incidence of SAEs and AEs by relationship and severity grade, and incidence of SAEs/AEs leading to dose reduction, interruption or discontinuation of study treatment.
• Pharmacokinetic parameters: Cmax, Cmin, AUC0-t, AUC0-¿, Tmax, elimination T½, and other secondary PK parameters of APL-101 in all subjects during Cycle 1, and APL-101 metabolites if applicable.
• Antitumor activity by clinical benefit rate (CR + PR + SD = 4 cycles) per RECIST v1.1. (or relevant criteria per tumor type).
• Median time to progression (TTP).
• Progression free survival (PFS) and overall survival (OS) at 6, 12, 18 and 24 months.

Obiettivi secondari della fase 1/2
• Valutare l’incidenza degli eventi avversi seri (SAE) e degli eventi avversi (EA) in base al rapporto e al livello di gravità, e incidenza di SAE/AE che portano ad una riduzione della dose, interruzione o discontinuazione del trattamento.
• Determinare i parametri farmacocinetici: Cmax, Cmin, AUC0-t, AUC0-¿, Tmax, T½ di eliminazione e parametri PK secondari di APL-101 in tutti i soggetti durante il Ciclo 1, e se possibile i metaboliti di APL-101.
• Valutare l'attività antitumorale in base a tasso di beneficio clinico (CBR: CR + PR + SD = 4 cicli), secondo i Criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1 (o i criteri di valutazione rilevanti per tipo di tumore).
• Tempo mediano di progressione (TTP)
• Sopravvivenza libera da progressione (PFS) e sopravvivenza globale (OS) a 6, 12, 18 e 24 mesi.

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoints are described within the text in section E.5.2

I punti temporali sono descritti all'interno del testo nella sezione E.5.2

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

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

Yes

E.6.10

Pharmacogenetic

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Therapeutic exploratory phase II

Fase II terapeutica esplorativa

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

Yes

E.8.1.7.1

Other trial design description

studio in aperto

open study

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

Information not present in EudraCT

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

Hong Kong

Russian Federation

Singapore

Taiwan

Ukraine

United States

Belgium

Finland

France

Germany

Hungary

Italy

Spain

United Kingdom

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

6-months post last subject treatment

6 mesi dopo il trattamento dell'ultimo soggetto

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:

121

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

201

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

nessuno

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

2020-06-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-08

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