Clinical Trials Register

Summary
EudraCT Number:	2019-003474-35
Sponsor's Protocol Code Number:	16-214-05
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-12-02
Trial results	View 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

Spain - AEMPS

A.2

EudraCT number

2019-003474-35

A.3

Full title of the trial

A Phase 1/2, Open-label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of NKTR-214 in Combination with Pembrolizumab in Patients with Locally Advanced or Metastatic Solid Tumors

Estudio de fase 1/2, abierto y multicéntrico para investigar la seguridad y la eficacia preliminar del NKTR-214 en combinación con pembrolizumab en pacientes con tumores sólidos localmente avanzados o metastásicos

A.3.1

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

A study to investigate the use of the study drug NKTR-214 in combination with Pembrolizumab for solid tumours.

Un estudio para investigar el uso del fármaco en investigación NKTR-214 en combinación con Pembrolizumab para tratar tumores sólidos.

A.3.2

Name or abbreviated title of the trial where available

PROPEL

A.4.1

Sponsor's protocol code number

16-214-05

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03138889

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	Nektar Therapeutics
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	Nektar Therapeutics
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	Nektar Therapeutics
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	455 Mission Bay Boulevard South
B.5.3.2	Town/ city	San Francisco
B.5.3.3	Post code	CA 94158
B.5.3.4	Country	United States
B.5.6	E-mail	studyinquiry@nektar.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	bempegaldesleukin
D.3.2	Product code	NKTR-214
D.3.4	Pharmaceutical form	Lyophilisate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	bempegaldesleukin
D.3.9.2	Current sponsor code	NKTR-214
D.3.9.3	Other descriptive name	BEMPEGALDESLEUKIN
D.3.9.4	EV Substance Code	SUB196365
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	1
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)	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 25 mg/mL concentrate for solution for infusion.
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Pembrolizumab
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEMBROLIZUMAB
D.3.9.3	Other descriptive name	PEMBROLIZUMAB
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)	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

Patients with with locally advanced or metastatic solid tumors.

Pacientes con tumores sólidos localmente avanzados o metastásicos

E.1.1.1

Medical condition in easily understood language

Patients with a solid tumor cancer that has grown or spread

Pacientes con un tumor sólido que haya crecido o se haya expandido.

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	10065143
E.1.2	Term	Malignant solid tumour
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To determine the ORR by RECIST 1.1 of NKTR-214 plus pembrolizumab in patients with untreated metastatic NSCLC.

• Determinar la TRO según los criterios RECIST 1.1 de NKTR-214 más pembrolizumab en pacientes con CPNM metastásico no tratado.

E.2.2

Secondary objectives of the trial

• To evaluate safety and tolerability of NKTR-214 plus pembrolizumab in patients with untreated NSCLC (Dose Expansion only).
• To assess the preliminary efficacy of NKTR-214 in combination with pembrolizumab:
- objective response rate (ORR) by RECIST 1.1
- duration of response (DOR) by RECIST 1.1
- clinical benefit rate (CBR) by RECIST 1.1
- time to response (TTR) by RECIST 1.1
- progression-free survival (PFS) by RECIST 1.1
- overall survival (OS)
• To assess the association between efficacy measures and PD-L1 expression in tumors.

• Evaluar la seguridad y tolerabilidad de NKTR-214 más pembrolizumab en pacientes con CPNM no tratado (solo expansión de la dosis).
• Evaluar la eficacia preliminar de NKTR-214 en combinación con pembrolizumab:ç- tasa de respuesta objetiva (TRO) según los criterios RECIST 1.1
- duración de la respuesta (DR) según los criterios RECIST 1.1
- tasa de beneficio clínico (TBC) según los criterios RECIST 1.1
- tiempo hasta la respuesta (TTR) según los criterios RECIST 1.1
- supervivencia sin progresión (SSP) según los criterios RECIST 1.1
- supervivencia global (SG)
• Evaluar la asociación entre las medidas de eficacia y la expresión de PD-L1 en tumores.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Provide written, informed consent to participate in the study and follow the study procedures.
• Age 18 years or older at the time of signing the informed consent form (ICF).
• Life expectancy > 12 weeks as determined by the Investigator.
• Patients may have received no more than one prior line of systemic therapy for locally advanced or metastatic cancer.
• Prior IL-2 therapy is allowed for patients in the dose optimization cohorts, but not in the dose expansion cohort.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Oxygen saturation ≥ 92% on room air for all indications; oxygen saturation ≥ 90% on room air for lung cancer considered to be due to lung metastasis.
• Measurable disease per RECIST 1.1.
• Patients with hypertension must be on ≤ 2 antihypertensive medications and without change for the 14 days prior to randomization. Screening blood pressure must be systolic < 150 mm Hg and < 90 mm Hg for diastolic blood pressure.
• A brain MRI at Screening is required for all patients with metastatic NSCLC, and for patients with other tumor types who have known brain metastasis.
• Patients with brain metastases are eligible if all the criteria below are fulfilled:
- Brain metastases must be treated at least 2 weeks prior to study treatment initiation. Treatment may include stereotactic radiosurgery, whole brain radiotherapy, or neurosurgical resection.
- Brain imaging after treatment and within the screening period must demonstrate no new or progressing brain metastases.
- No requirement for systemic corticosteroids >10 mg/day prednisone equivalents. Stable doses of anticonvulsants are allowed.
- No clinically significant symptoms associated with brain metastases.
• Tumor tissue sample is required for all patients. Acceptable samples include archival tissue obtained no more than 12 months prior to enrollment if the patient has not received systemic treatment between the time of biopsy/resection and enrollment. Otherwise, a fresh tumor biopsy taken during screening is required.
Dose Expansion Cohort (Cohort 2)
1L Non- Small Cell Lung Cancer (Cohorts 2.1, 2.2, and 2.3)
• Histologically or cytologically confirmed diagnosis of NSCLC.
• Patients must have tumor tissue samples available and sent to a central laboratory for PD-L1 testing using an FDA-approved test or validated assay. Approximately 20 patients will be enrolled in each subgroup of PD-L1 negative (PD-L1 < 1%; Cohort 2.1), PD-L1 low/intermediate (PD-L1 1% to 49%; Cohort 2.2) or PD-L1 highly positive (PD-L1 ≥ 50%; Cohort 2.3).
• Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations are excluded.
• Must not have received anti-cancer therapy for advanced or metastatic lung cancer.
• Must not have progressed on or within 6 months of completing adjuvant PD-L1 therapy.

• Proporcionar el consentimiento informado por escrito para participar en el estudio y seguir los procedimientos del estudio.
• Edad igual o superior a 18 años en el momento de firmar el formulario de consentimiento informado (FCI).
• Esperanza de vida > 12 semanas según lo determinado por el investigador.
• Los pacientes no pueden haber recibido más de una línea previa de tratamiento sistémico para el cáncer localmente avanzado o metastásico.
• Se permite el tratamiento previo con IL-2 en los pacientes de las cohortes de optimización de la dosis, pero no en la cohorte de ampliación de la dosis.
• Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1.
• Saturación de oxígeno ≥ 92 % en aire ambiente para todas las indicaciones; saturación de oxígeno ≥ 90 % en aire ambiente para el cáncer de pulmón debida a metástasis pulmonares.
• Enfermedad mensurable según RECIST 1.1.
• Los pacientes con hipertensión deben recibir ≤ 2 medicamentos antihipertensivos y sin cambios durante los 14 días previos a la aleatorización. La presión arterial en la selección debe ser sistólica < 150 mm Hg y < 90 mm Hg para la presión arterial diastólica.
• Se requiere una RM cerebral en la selección para todos los pacientes con CPNM metastásico y para los pacientes con otros tipos de tumores que tengan metástasis cerebrales conocidas.
• Los pacientes con metástasis cerebrales pueden ser seleccionados si cumplen todos y cada uno de los criterios siguientes:
- Las metástasis cerebrales deben tratarse al menos 2 semanas antes del inicio del tratamiento del estudio. El tratamiento puede incluir radiocirugía estereotáctica, radioterapia de cerebro completo o resección neuroquirúrgica.
- La obtención de imágenes cerebrales después del tratamiento y en el período de selección no debe contener metástasis cerebrales nuevas o en progresión.
- Sin necesidad de corticosteroides sistémicos > 10 mg/día de equivalentes de prednisona. Se permiten dosis estables de anticonvulsivos.
- Sin síntomas clínicamente significativos asociados a metástasis cerebrales
• Se requiere una muestra de tejido tumoral para todos los pacientes. Las muestras aceptables incluyen tejido de archivo obtenido no más de 12 meses antes de la inscripción si el paciente no ha recibido tratamiento sistémico entre el momento de la biopsia/resección y la inscripción. De lo contrario, se requiere una nueva biopsia tumoral obtenida durante la selección.
Cohorte de ampliación de la dosis (cohorte 2)
• Diagnóstico de CPNM confirmado histológica o citológicamente.
• Los pacientes deben disponer de muestras de tejido tumoral y enviarse a un laboratorio central para el análisis de PD-L1 mediante una prueba aprobada por la FDA o un ensayo validado. Se inscribirán aproximadamente 20 pacientes en cada subgrupo de PD-L1 negativo (PD-L1 < 1%; cohorte 2.1), PD-L1 bajo/intermedio (PD-L1 1% al 49%; cohorte 2.2) o PD-L1 muy positivo (PD-L1 ≥ 50%; cohorte 2.3).
• Se excluyen los pacientes con aberraciones genómicas del receptor del factor de crecimiento epidérmico (EGFR) o de la cinasa del linfoma anaplásico (ALK).
• No debe haber recibido tratamiento antineoplásico para el cáncer de pulmón avanzado o metastásico.
• No debe haber progresado durante o en los 6 meses posteriores a la finalización del tratamiento adyuvante con PD-L1.

E.4

Principal exclusion criteria

1. Use of an investigational agent or an investigational device within 28 days prior to enrollment.
2. Women who are pregnant or breastfeeding.
3. Patients who have an active, known or suspected autoimmune disease. Exceptions include patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, autoimmune conditions not expected to recur, or with Medical Monitor approval.
4. History of allergy or hypersensitivity to study drug components.
5. Prior malignancy within the previous 3 years. Exceptions include non-melanoma skin cancer and carcinoma in situ of bladder, breast, cervix, colon, prostate, stomach, and melanoma treated with curative intent, with minimal risk of recurrence or requiring therapy during study participation. Patients with prostate cancer are allowed if one of the following criteria is met:
Stage T2N0M0 or lower; Gleason score ≤ 3+4, and prostate-specific antigen (PSA) below lower limit of normal by local laboratory.
6. Patients in the dose expansion cohort must not have received prior IL-2 therapy.
7. Chronic systemic corticosteroid at >10 mg prednisone or equivalent or other immunosuppressive agents. Patient on inhaled steroids for asthma or local steroid injections are allowed.
8. Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
9. Surgery or radiotherapy within 14 days of enrollment. Patients who had surgery or radiotherapy outside of 14 days must have recovered from associated complications and toxicities.
10. Chemotherapy or biological therapy within 28 days of enrollment. Targeted therapy (e.g., tyrosine kinase inhibitors) within 14 days of enrollment.
11. Prior treatment with immune checkpoint inhibitor.
12. Active infection requiring systemic therapy.
13. Known hepatitis B virus (HBV) infection (e.g., positive hepatitis B surface antigen [HBsAg]) or hepatitis C virus (HCV) infection (e.g., positive HCV ribonucleic acid [RNA]).
14. Known immunodeficiency or active human immunodeficiency virus (HIV-1/2 antibodies).
15. Prolonged Fridericia’s corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening.
16. History of unstable or deteriorating cardiac disease or cerebrovascular disease within the 2 years prior to screening including but not limited to the following:
a. Unstable angina or myocardial infarction.
b. Congestive heart failure (New York Heart Association [NYHA] Class III or IV).
c. Uncontrolled clinically significant arrhythmias.
d. Cerebrovascular accident or transient ischemic attack
17. Current drug or alcohol abuse.
18. Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator, would preclude the patient from adhering to the protocol or would increase the risk of adverse events while participating in study.

1. Uso de un agente o dispositivo experimental en un período inferior a 28 días antes del inicio de la participación.
2. Mujeres embarazadas o en período de lactancia.
3. Pacientes que tengan sospecha de una enfermedad autoinmunitaria activa o que padezcan una enfermedad autoinmunitaria activa conocida. Entre las excepciones se encuentran pacientes con diabetes mellitus tipo I, hipotiroidismo que solamente requiera sustitución hormonal, trastornos cutáneos (como vitíligo, soriasis o alopecia) que no requieran tratamiento sistémico, enfermedades autoinmunes de las que no se espere recurrencia o aquellas que tengan la aprobación del monitor médico.
4. Antecedentes de alergia o hipersensibilidad a los componentes del medicamento del estudio.
5. Malignidad en los últimos 3 años. Entre las excepciones se incluye cáncer de piel no melanoma y carcinoma in situ de vejiga, pecho, cérvix, colon, próstata, estómago y melanoma tratado con intención curativa, con mímimo riesgo de recurrencia o que requiera tratamiento durante el período de participación en el estudio. Los pacientes con cáncer de próstata pueden participar si se cumple uno de los siguientes criterios: estadio T2N0M0 o menor; puntuación de Gleason ≤ 3+4 y antígeno prostático específico (PSA) por debajo del límite normal determinado en el laboratorio local.
6. Los pacientes de la cohorte de la dosis de expansión no pueden haber recibido tratamiento con IL-2 anteriormente.
7. Corticosteroide sistémico crónico a > 10 mg de prednisona o equivalente u otros agentes inmunosupresores. Se les permite participar a los pacientes que inhalen esteroides para el asma o que se inyecten esteroides de manera local.
8. Evidencia de enfermedad pulmonar intersticial clínicamente importante o neumonitis no infecciosa activa.
9. Cirugía o radioterapia en los 14 días anteriores al día de inicio de la participación en el estudio. Aquellos pacientes que hayan sido sometidos a cirugía o radioterapia en un período superior a los 14 días mencionados tienen que haberse recuperado de las complicaciones y toxicidades asociadas.
10. Quimioterapia o terapia biológica en los 28 días anteriores al día de inicio de la participación en el estudio. Terapia dirigida (por ejemplo, inhibidores de la tirosina cinasa) en los 14 días anteriores al día de inicio de la participación en el estudio.
11. Tratamiento anterior con inhibidor inmune de control.
12. Infección activa que precise tratamiento sistémico.
13. Infección conocida de virus de la hepatitis B (VHB) (por ejemplo, antígeno de superficie de la hepatitis B positiva [HBsAg]) o infección de virus de la hepatitis C (VHC) (por ejemplo, ácido ribonucleico [ARN] positivo del VHC).
14. Inmunodeficiencia conocida o virus de inmunodeficiencia humano activo (anticuerpos contra el VIH 1/2).
15. Prolongación del intervalo QT con corrección de Fridericia (QTcF) > 450 ms en hombres y > 470 ms en mujeres en la selección.
16. Antecedentes de cardiopatía inestable o deteriorante o enfermedad cerebrovascular en los 2 años previos a la selección incluyendo, entre otros, los siguientes:
a. Angina de pecho inestable o infarto de miocardio.
b. Insuficiencia cardíaca congestiva de las clases III o IV según la Asociación de Cardiología de Nueva York (New York Heart Association, NYHA).
c. Arritmias clínicamente importantes no controladas.
d. Accidente cerebrovascular o ataque isquémico transitorio.
17. Toxicomanía o alcoholismo en la actualidad.
18. Cualquier trastorno médico, emocional, psiquiátrico o logístico que, según criterio del investigador, impida al paciente cumplir el protocolo o aumente el riesgo de que se produzcan eventos adversos durante la participación en el estudio.

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint :
- ORR by RECIST 1.1 of NKTR-214 plus pembrolizumab in patients with untreated metastatic NSCLC

Criterios principales:
- Tasa de respuesta objetiva (TRO) de NKTR-214 con pembrolizumab en pacientes con tumores sólidos localmente avanzados o metastásicos.

E.5.1.1

Timepoint(s) of evaluation of this end point

Screening then every 9 weeks (± 7 days) from Cycle 1 Day 1, EOT (unless scan done within 4 weeks) and at the 90-day long-term follow-up visits

Las mediciones tumorales se realizarán cada 9 semanas ± 7 días desde el día 1 del ciclo 1, en el FdT (a menos que se haya hecho un scan en las 4 semanas anteriores) y en las consultas de seguimiento a largo plazo a los 90 días.

E.5.2

Secondary end point(s)

Efficacy endpoints : Tumor response evaluation :
- duration of response (DOR) by RECIST 1.1
- clinical benefit rate (CBR) by RECIST 1.1
- time to response (TTR) by RECIST 1.1
- progression-free survival (PFS) by RECIST 1.1
- overall survival (OS)
Secondary Safety endpoints :
incidence of adverse events (AEs), including serious AEs (SAEs)
- clinical laboratory tests (blood and urine sampling)
- vital signs
- electrocardiograms (ECG) and echocardiograms (ECHO) or multigated acquisition (MUGA)
- physical examination

Criterios de eficacia: evaluación de respuesta tumoral:
- duración de la respuesta (DR) según RECIST 1.1
- tasa de beneficio clínico (TBC) según RECIST 1.1
- tiempo transcurrido hasta la respuesta (TTR) según RECIST 1.1
- supervivencia sin progresión (SSP)
- supervivencia global (SG)
Criterios secundarios de seguridad:
- Incidencia de acontecimientos adversos (AA), incluidos los AA graves (AAG)
- Pruebas analíticas (muestras de sangre y orina)
- Constantes vitales
- Electrocardiogramas (ECg) y ecocardiogramas (eco) o ventriculografía isotópica
- Exploración física

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy: screening then every 9 weeks (± 7 days) from Cycle 1 Day 1, EOT (unless scan done within 4 weeks) and at the 90-day long-term follow-up visits
Safety: Throughout the study

Eficacia: Las mediciones tumorales se realizarán cada 9 semanas ± 7 días, en el FdT y en las consultas de seguimiento a largo plazo a los 90 días.
Seguridad: A lo largo del estudio

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

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)

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

Phase 1/2

Fase 1/2

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

Australia

Belgium

France

Germany

Hungary

Israel

Italy

Netherlands

Russian Federation

Spain

United Kingdom

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

End of study is defined as no more than 3 years after the last patient received their first dose of NKTR-214, lost to follow-up, or Sponsor decision to terminate the study, whichever comes first. Survival data may be collected beyond end of study.

El final del estudio se define como no más de 3 años tras la última dosis de NKTR-214 del último paciente, la pérdida de seguimiento o la decisión del Promotor de terminar el estudio, lo que ocurra primero. Los datos de supervivencia deberán recogerse después del fin del estudio.

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)

The investigator will treat the subject as per institution best practice. Treatment with NKTR-214 may continue beyond progression if there is clinical benefit as determined by the Investigator.

El investigador tratará al paciente siguiendo la mejor práctica del centro. El tratamiento con NKTR-214 continuará después de la progresión si el investigador determina que hay beneficio clínico.

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

2020-02-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-02-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-07-05

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