Clinical Trials Register

Summary
EudraCT Number:	2021-006692-42
Sponsor's Protocol Code Number:	GCT1053-01
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:	2022-07-11
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

2021-006692-42

A.3

Full title of the trial

First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate the safety of GEN1053 as monotherapy and in combination with an immunomodulator in subjects with malignant solid tumors

Primer ensayo clínico en seres humanos, abierto, de escalada de dosis con cohortes de ampliación para evaluar la seguridad de GEN1053 en monoterapia y en combinación con un inmunomodulador en pacientes con tumores sólidos malignos

A.3.1

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

A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy and in Combination

Estudio para evaluar la seguridad, la tolerabilidad y el efecto preliminar del anticuerpo GEN1053 en tumores sólidos malignos como monoterapia y en combinación

A.4.1

Sponsor's protocol code number

GCT1053-01

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	Genmab B.V.
B.1.3.4	Country	Netherlands
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	Genmab B.V.
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genmab B.V.
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Uppsalalaan 15
B.5.3.2	Town/ city	Utrect
B.5.3.3	Post code	3584 CT
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+34917567825
B.5.6	E-mail	clinicaltrials@genmab.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	HexaBody®CD-27
D.3.2	Product code	GEN1053
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	GEN1053-DS
D.3.9.1	CAS number	2733575-82-9
D.3.9.2	Current sponsor code	GEN1053
D.3.9.3	Other descriptive name	HexaBody®CD-27
D.3.9.4	EV Substance Code	SUB269328
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	20
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

Malignant Solid Tumors, per protocol GCT1053-01

Tumores sólidos malignos, por protocolo GCT1053-01

E.1.1.1

Medical condition in easily understood language

Solid Tumor

Tumor sólido

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	10065147
E.1.2	Term	Malignant solid tumor
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

•Determine MTD/MAD/RP2Ds of GEN1053 as monotherapy and in combination with immunomodulator
•Establish initial safety profile of GEN1053 as monotherapy and in combination with immunomodulator

•Determinar la DMT/DMA/DRF2 de GEN1053 en monoterapia y en combinación con IM
• Establecer el perfil de seguridad inicial de GEN1053 en monoterapia y en combinación con IM

E.2.2

Secondary objectives of the trial

•Establish pharmacokinetic (PK) profile of GEN1053 as monotherapy and in combination with immunomodulator
•Evaluate immunogenicity of GEN1053 as monotherapy and in combination with immunomodulator
•Evaluate antitumor activity of GEN1053 as monotherapy and in combination with immunomodulator

• Establecer el perfil farmacocinético (FC) de GEN1053 en monoterapia y en combinación con inmunomodulador
• Evaluar la inmunogenicidad de GEN1053 en monoterapia y en combinación con Inmunomodulador
• Evaluar la actividad antitumoral de GEN1053 en monoterapia y en combinación con inmunomodulador

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

For both the Dose Escalation and Expansion parts:
Subject must:
•Be ≥18 years of age.
•Have measurable disease according to RECIST 1.1
•Provide all pre-baseline scans since failure of last prior therapy (ie documented radiographic PD), if available
•Have Eastern Cooperative Oncology Group performance status ≤1.
•Have organ and bone marrow function as follows:
Bone marrow / hematological function:
▪Absolute neutrophil count (ANC) ≥1.5×109/L
▪Hemoglobin ≥9.0 g/dL
▪Platelet count ≥150×109/L
Liver function:
▪Total bilirubin ≤ upper limit of normal (ULN)
▪Alanine aminotransferase ≤1.5×ULN
▪Aspartate aminotransferase ≤1.5×ULN
▪Albumin ≥30 g/L
Coagulation status:
▪Prothrombin time (PT)/International normalized ratio ≤1.5
▪Activated partial thromboplastin time (aPTT) ≤1.5×ULN
Renal function: Glomerular filtration rate ≥45 mL/min/1.73 m², according to the abbreviated Modification of Diet in Renal Disease equation

For Monotherapy Dose Escalation (phase 1a) and Combination therapy Dose Escalation (phase 1b) only:
•Subjects with histologically or cytologically confirmed non-CNS solid tumors that are metastatic or advanced.
•Subjects for whom there is no available standard therapy likely to confer clinical benefit, or who are not candidates for or refuse such available therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1053 or GEN1053+IM may be beneficial.
•Fresh biopsies mandatory for all patients in Monotherapy Dose Escalation and Combination therapy Dose Escalation

For the Expansion part Only:
•Subjects with histologically or cytologically confirmed diagnosis of recurrent, unresectable or metastatic HNSCC or metastatic NSCLC, who do not have any further available standard therapy or are not candidates for or refuse standard therapy (if subjects had access), and for whom experimental therapy with GEN1053 or GEN1053+IM may be beneficial, in the opinion of the investigator.

Tanto para la parte de aumento gradual de la dosis como para la parte de expansión
El participante debe:
• Tener ≥18 años.
• Presentar una enfermedad medible según RECIST 1.1.
• Proporcionar todas las exploraciones previas al inicio desde el fracaso del último tratamiento anterior (es decir, EP radiográfica documentada), si está disponible.
• Presentar estado funcional según el Grupo Oncológico Cooperativo del Este ≤1.
• Presentar función orgánica y de la médula ósea como sigue:
○ Función hematológica/de la médula ósea:
▪ Cifra absoluta de neutrófilos (CAN) ≥1,5 × 109/l
▪ Hemoglobina ≥9,0 g/dl
▪ Cifra de trombocitos ≥150 × 109/l
○ Función hepática:
▪ Bilirrubina total ≤ límite superior de la normalidad (LSN)
▪ Alanina aminotransferasa ≤1,5 × LSN
▪ Aspartato aminotransferasa ≤1,5 × LSN
▪ Albúmina ≥30 g/l
○ Estado de coagulación:
▪ Tiempo de protrombina (TP)/índice internacional normalizado ≤1,5
▪ Tiempo de tromboplastina parcial activada (TTPa) ≤1,5 × LSN
○ Función renal:
Tasa de filtración glomerular ≥45 ml/min/1,73 m², según la ecuación abreviada de modificación de la dieta en la enfermedad renal

Solamente para el aumento gradual de la dosis en monoterapia (fase Ia) y el aumento gradual de la dosis del tratamiento combinado (fase Ib):
• Participantes con tumores sólidos avanzados o metastásicos confirmados histológica o citológicamente con localización distinta del SNC.
• Pacientes para los que no existe ningún tratamiento estándar disponible que pueda conferir un beneficio clínico, o que no son candidatos o rechazan dicho tratamiento disponible y para los que, en opinión del investigador, el tratamiento experimental con GEN1053 o GEN1053+IM podría ser beneficioso.
• Biopsias para el aumento gradual de la dosis en monoterapia y para el aumento gradual de la dosis del tratamiento combinado

Solo para la parte de expansión:
• Los participantes con diagnóstico confirmado histológica o citológicamente de CECC recurrente, irresecable o metastásico, que no tengan ningún tratamiento estándar disponible o no sean candidatos o rechacen el tratamiento estándar (si los participantes tenían acceso) y para los que el tratamiento experimental con GEN1053 (CECC) o GEN1053+IM

E.4

Principal exclusion criteria

•Has uncontrolled intercurrent illness, including but not limited to:
-Ongoing or active infection requiring IV treatment with anti-infective therapy administered less than 2 weeks prior to first dose.
-Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.
-Uncontrolled hypertension defined as systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, despite optimal medical management.
-Ongoing or recent (within 1 year) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs.
-History of grade 3 or higher irAEs that led to treatment discontinuation of a CPI.
-History of chronic liver disease or evidence of hepatic cirrhosis.
-Evidence of interstitial lung disease.
-Ongoing pneumonitis or history of non-infectious pneumonitis that has required steroids.
-Known platelet function defects.
•Prior therapy:
-Radiotherapy within 14 days prior to first GEN1053 administration. Palliative radiotherapy will be allowed.
-Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1053 administration.
-Subject with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment. Inhaled or topical steroids, and adrenal or pituitary replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Presentar una enfermedad intercurrente no controlada, incluidas, entre otras:
○ Infección en curso o activa que requiera tratamiento i.v. con un tratamiento antiinfeccioso administrado menos de 2 semanas antes de la primera dosis.
○ Insuficiencia cardíaca congestiva sintomática (de grado III o IV según la clasificación de la New York Heart Association), angina de pecho inestable o arritmia cardíaca.
○ Hipertensión no controlada definida como presión arterial sistólica ≥160 mmHg y/o presión arterial diastólica ≥100 mmHg, a pesar de un tratamiento médico óptimo.
○ Indicios recientes o en curso (en el plazo de 1 año antes de la selección) de enfermedad autoinmunitaria significativa que requiriera tratamiento con inmunodepresores sistémicos, lo que podría sugerir riesgo de AAri.
○ Antecedentes de AAri de grado 3 o superior que provocaron la interrupción del tratamiento de un IPC.
○ Antecedentes de enfermedad hepática crónica o indicios de cirrosis hepática.
○ Signos de enfermedad pulmonar intersticial.
○ Neumonitis en curso o antecedentes de neumonitis no infecciosa que haya necesitado corticoesteroides.
○ Defectos conocidos de la función plaquetaria.
• Tratamiento anterior:
○ Radioterapia en los 14 días previos a la primera administración de GEN1053. Se permitirá la radioterapia paliativa.
○ Tratamiento con un agente antineoplásico (en el plazo de 28 días o después de al menos 5 semividas del fármaco, lo que sea más corto), antes de la administración de GEN1053.
○ Afección que requiera tratamiento sistémico con corticoesteroides (>10 mg al día de equivalente de prednisona) u otros medicamentos inmunodepresores en los 14 días anteriores al primer tratamiento. Se permiten los corticoesteroides inhalados o tópicos y los corticoesteroides de sustitución suprarrenal o hipofisaria equivalentes a >10 mg al día de prednisona, en ausencia de enfermedad autoinmunitaria activa.

E.5 End points

E.5.1

Primary end point(s)

•Dose-limiting toxicities (DLTs), (Dose Escalation parts only)
•Adverse events (AEs) and safety laboratory parameters

•Toxicidades limitantes de dosis (DLT), (solo para la parte de escalada de de dosis)
•Eventos adversos (EA) y parámetros de laboratorio de seguridad

E.5.1.1

Timepoint(s) of evaluation of this end point

Assessments will be performed at regular intervals during the trial.
A final safety follow-up visits will be conducted 30 days and 60 days after the subject receives the last dose of IMP. Thereafter, survival status will be assessed by contacting subjects every 12 weeks after last dose and continuing until the subject dies or withdraws from the trial.

Las evaluaciones se realizarán a intervalos regulares durante el ensayo.
Se realizarán visitas finales de seguimiento de seguridad 30 días y 60 días después de que el sujeto reciba la última dosis de IMP. Posteriormente, el estado de supervivencia se evaluará contactando a los sujetos cada 12 semanas después de la última dosis y continuando hasta que el sujeto muera o se retire del ensayo.

E.5.2

Secondary end point(s)

•PK parameters: clearance, volume of distribution, maximum concentration, time of Cmax, predose trough concentrations, half-life, area under the concentration-time curve
•Anti-drug antibody response of GEN1053 and in combination with immunomodulator
Antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1:
•Objective response rate (ORR)
•Disease control rate (DCR)
•Duration of response (DOR)

•Parámetros farmacocinéticos: aclaramiento, volumen de distribución, concentración máxima, tiempo de Cmax, concentraciones mínimas previas a la dosis, vida media, área bajo la curva de concentración-tiempo
•Respuesta de anticuerpos antidrogas de GEN1053 y en combinación con inmunomodulador
Actividad antitumoral según Response Evaluation Criteria in Solid Tumors (RECIST) 1.1:
• Tasa de respuesta objetiva (ORR)
•Tasa de control de enfermedades (DCR)
•Duración de la respuesta (DOR)

E.5.2.1

Timepoint(s) of evaluation of this end point

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

E.6.11

Pharmacogenomic

Yes

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

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

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

United States

France

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

The end of trial is defined as when the last subject dies or withdraws from the trial globally. However, the maximum global trial duration is 5 years after the last subject’s first treatment .

El final del ensayo se define como cuando el último sujeto muere o se retira del ensayo globalmente. Sin embargo, la duración máxima del ensayo global es de 5 años después del primer tratamiento del último sujeto.

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:

113

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

170

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)

Post trial treatment is at the discretion of the patient's doctor per standard of care per country. The sponsor will make their best effort to provision post-trial access to to GEN1053 and immunomodulator for those ongoing subjects with a potential treatment benefit, in accordance with local laws and requirements.

El tratamiento posterior al ensayo queda a discreción del médico del paciente según el estándar de atención por país. El promotor hará todo lo posible para proporcionar acceso posterior al ensayo a GEN1053 e inmunomodulador para aquellos sujetos en curso con un posible beneficio de tratamiento, de acuerdo con las leyes y los requisitos locales.

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

2022-08-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-15

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

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