Clinical Trials Register

Summary
EudraCT Number:	2020-005170-10
Sponsor's Protocol Code Number:	COMBI-TED
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-08-02
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

Spain - AEMPS

A.2

EudraCT number

2020-005170-10

A.3

Full title of the trial

A multicenter, Phase II, open label, randomized trial evaluating the efficacy of Tedopi plus docetaxel or Tedopi plus nivolumab as second-line therapy in metastatic non-smallcell lung cancer progressing after first-line chemo-immunotherapy (Combi-TED)

Ensayo multicéntrico, de fase II, abierto y aleatorizado para evaluar la
eficacia de Tedopi y docetaxel o Tedopi y nivolumab como tratamiento de
segunda línea en el cáncer de pulmón de células no pequeñas metastásico y
en progresión tras el tratamiento de primera línea con
quimioinmunoterapia (Combi-TED)

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

COMBI-TED

A.4.1

Sponsor's protocol code number

COMBI-TED

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 RICERCA TRASLAZIONALE (FORT)
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	OSE Immunotherapeutics
B.4.2	Country	France
B.4.1	Name of organisation providing support	Bristol Myer Squibb International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Clinical Research Technology
B.5.2	Functional name of contact point	Paola Schiavo
B.5.3	Address:
B.5.3.1	Street Address	Via San Leonardo trav. Migliaro
B.5.3.2	Town/ city	Salerno
B.5.3.3	Post code	84131
B.5.3.4	Country	Italy
B.5.6	E-mail	combi-ted@cr-technology.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	TEDOPI
D.3.2	Product code	OSE2101
D.3.4	Pharmaceutical form	Emulsion for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	TEDOPI
D.3.9.3	Other descriptive name	OSE2101
D.3.9.4	EV Substance Code	SUB191632
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	5
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	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	OPDIVO
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL-MYERS SQUIBB PHARMA EEIG
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	NIVOLUMAB
D.3.2	Product code	BMS-936558
D.3.4	Pharmaceutical form	Concentrate for solution for injection/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	Nivolumab
D.3.9.1	CAS number	946414-94-4
D.3.9.2	Current sponsor code	BMS-936558
D.3.9.3	Other descriptive name	MDX1106, ONO-4538
D.3.9.4	EV Substance Code	SUB32944
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	10
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	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

metastatic non-small-cell lung cancer

cáncer de pulmón de células no pequeñas metastásico

E.1.1.1

Medical condition in easily understood language

metastatic non-small-cell lung cancer

cáncer de pulmón de células no pequeñas metastásico

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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

To assess 1-year survival rate in patients treated with Tedopi plus docetaxel (arm A) or Tedopi plus nivolumab (arm B) or docetaxel as single agent (arm C) in subjects with advanced NSCLC progressing on first-line chemoimmunotherapy.

Evaluar la supervivencia global (SG) a un año en pacientes tratados con
Tedopi más docetaxel (brazo A) y Tedopi más nivolumab (brazo B) o docetaxel como agente único (brazo C).

E.2.2

Secondary objectives of the trial

• To assess Overall Survival (OS)
• To assess Progression-free survival (PFS)
• To assess Objective Response Rate (ORR)
• To assess treatment safety
Exploratory
• To assess correlation of ORR, PFS and OS with biomarkers in tumor tissue or blood.

• Evaluación de la SG (OS, por sus siglas en inglés) general.
• Evaluación de la supervivencia sin progresión (SSP, o PFS
Progression-free survival).
• Evaluación de la tasa de respuesta objetiva (TRO, o ORR por sus siglas
en inglés).
• Evaluación de la seguridad del tratamiento.
• Evaluar la correlación entre la TRO, la SSP, la SG y los biomarcadores en sangre y tejido tumoral.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female patients willing and able to give written informed consent;
2. Histological or cytological confirmed diagnosis of HLA-A2+ NSCLC with no evidence of
EGFR mutations or ALK or ROS1 rearrangement;
3. Evidence of disease progression at the end of at least 4 cycles of chemo-
immunotherapy or 2 cycles of chemo-immunotherapy followed by 2 cycles
of immunotherapy (CheckMate9LA regimen) and eligible for treatment
with docetaxel. Any chemotherapy is allowed, including chemotherapy
containing platinum salts. This criterion implies that patients with
immunotherapy primary resistance are excluded;
4. Patients must have experienced progressive disease (PD), either during or within 3
months of discontinuing treatment with anti-PD-(L)1-based therapy, occurring after
previous clear benefit (any complete –CR- or partial response -PR), or after previous
stable disease (SD);
5. Performance status 0-1 (ECOG);
6. Patient compliance to trial procedures;
7. Age > or = 18 years;

1. Pacientes masculinos y femeninos dispuestos y capaces de dar su
consentimiento informado por escrito;
2. Diagnóstico histológico o citológico confirmado de CPCNP HLA-A2+
sin evidencia de mutaciones del EGFR o reordenamientos de ALK o ROS1;
3. Evidencia de progresión de la enfermedad al final de al menos 4 ciclos
de quimioinmunoterapia o 2 ciclos de quimioinmunoterapia seguidos
de 2 ciclos de inmunoterapia (régimen CheckMate9LA), y apto para el
tratamiento con docetaxel. Se permite cualquier quimioterapia,
incluida la que contiene sales de platino. Este criterio significa que se
excluyen los pacientes con resistencia primaria a la inmunoterapia;
4. Los pacientes deben haber experimentado una progresión de la
enfermedad (PE), durante o dentro de los 3 meses siguientes a la
interrupción del tratamiento con anti-PD-(L)1, que se produzca
después de un claro beneficio (respuesta completa -CR- o respuesta
parcial -PR-), o después de una enfermedad estable (EE);
5. Estado de rendimiento 0-1 (ECOG);
6. El paciente respeta los procedimientos del estudio;
7. Edad> o = 18 años;

E.4

Principal exclusion criteria

1. Patient positive for actionable EGFR mutations or ALK or ROS1 rearrangement;
2. No previous chemoimmunotherapy for metastatic disease or evidence of disease
progression during the first 4 cycles of chemoimmunotherapy (primary resistance).
Patients with adjuvant resistance (documented loco-regionally and/or systemic relapse of
their disease occurring <6 months after the last dose of anti-PD-(L)1-based systemic
adjuvant therapy) are excluded;
3. Patients with intervening systemic therapy following prior anti-PD-(L)1-based
therapy;
4. Symptomatic brain metastases. Asymptomatic brain metastases are allowed if not
requiring corticosteroids use at a dose >10mg daily prednisone (or equivalent);
5. Diagnosis of any other malignancy during the last 3 years, except for in situ
carcinoma of cervix uteri and cutaneous squamous cell carcinoma or other local tumors
considered cured;
6. Pregnancy or lactating;

1. Paciente positivo para mutaciones del EGFR o reordenamiento ALK o
ROS1.
2. Sin quimioinmunoterapia previa para la enfermedad metastásica o
evidencia de progresión de la enfermedad durante los primeros 4 ciclos
de quimioinmunoterapia (resistencia primaria). Se excluyen los
pacientes con resistencia adyuvante (recidiva documentada de la
enfermedad locorregional y/o sistémica que se produce < 6 meses
después de la última dosis de tratamiento sistémico adyuvante basado
en anti-PD-(L)1).
3. Pacientes en terapia sistémica intermedia después de una terapia
previa con anti-PD- (L) 1.
4. Metástasis cerebrales sintomáticas. Las metástasis cerebrales
asintomáticas están permitidas si no requieren corticosteroides. 5. Diagnóstico de cualquier otro tumor maligno en los últimos 3 años,
excepto el carcinoma in situ de cuello uterino y el carcinoma
escamocelular cutáneo u otros tumores locales considerados curados
(por ejemplo, carcinoma de próstata localizado y presuntamente
curado).
6. Embarazo o lactancia.

E.5 End points

E.5.1

Primary end point(s)

1-year Survival Rate

Tasa de supervivencia a un año

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year

1 año

E.5.2

Secondary end point(s)

• Overall Survival (OS) (1 and 2-year OS)
• Progression-free survival (PFS) (1 and 2-year PFS)
• Objective Response rate (ORR)
• Safety
Exploratory
• Correlation of ORR, PFS and OS with tumor biomarkers

• Supervivencia global (SG) (mediana, SG a 1 y 2 años)
• Supervivencia sin progresión (SSP) (SSP a 1 y 2 años)
• Tasa de respuesta objetiva (TRO)
• Seguridad
Exploratorio
• Correlación entre TRO, SSP, SG y biomarcadores en sangre y tejido
tumoral.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 and 2 years
1 and 2 years
Every 8 weeks
Every 3 weeks
Exploratory: 48 months

1 y 2 años
1 y 2 años
Cada 8 semanas
Cada 3 semanas
Exploratorio: 48 meses

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

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

E.8.1.1

Randomised

Yes

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

Última visita del último paciente

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 months

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

105

F.4.2.2

In the whole clinical trial

105

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)

A safety follow up will be performed 30 days since last dose. A contact follow up will be performed every 3 months until the study termination.

Se realizará un seguimiento de seguridad 30 días después de la última dosis. Se realizará un seguimiento de contacto cada 3 meses hasta la finalización del estudio.

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

2022-08-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-29

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

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