Clinical Trials Register

Summary
EudraCT Number:	2021-001695-42
Sponsor's Protocol Code Number:	CAN04CLIN004
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-07-02
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

2021-001695-42

A.3

Full title of the trial

A Phase 1/2 study of CAN04, a fully humanised monoclonal antibody against IL1RAP, in combination with different chemotherapy regimens in subjects with advanced solid tumours

Estudio de fase 1/2 de CAN04, un anticuerpo monoclonal totalmente humanizado frente a IL1RAP, en combinación con diferentes pautas de quimioterapia en sujetos con tumores sólidos avanzados

A.3.1

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

A trial to assess the safety and efficacy of multiple doses of the CAN04 antibody in combination with different chemotherapy, in patients with advanced solid tumors.

Estudio para evaluar la seguridad y eficacia de múltiples dosis del anticuerpo CAN04, en combinación con diferentes pautas de quimioterapia, en pacientes con tumores sólidos avanzados.

A.4.1

Sponsor's protocol code number

CAN04CLIN004

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	Cantargia AB
B.1.3.4	Country	Sweden
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	Cantargia AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PPD
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	Fleming House, Phoenix Crescent, Strathclyde Business Park
B.5.3.2	Town/ city	Bellshill
B.5.3.3	Post code	ML4 3NJ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	34900 834 223
B.5.6	E-mail	RegistroEspanolDeEstudiosClinicos@druginfo.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	CAN04
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	Nadunolimab
D.3.9.2	Current sponsor code	CAN04
D.3.9.3	Other descriptive name	FULLY HUMANIZED LOW FUCOSE IGG1Κ MONOCLONAL ANTIBODY TARGETING IL1RAP
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	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	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	CAN04
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	Nadunolimab
D.3.9.2	Current sponsor code	CAN04
D.3.9.3	Other descriptive name	FULLY HUMANIZED LOW FUCOSE IGG1Κ MONOCLONAL ANTIBODY TARGETING IL1RAP
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	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: 3
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	CAN04
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	Nadunolimab
D.3.9.2	Current sponsor code	CAN04
D.3.9.3	Other descriptive name	FULLY HUMANIZED LOW FUCOSE IGG1Κ MONOCLONAL ANTIBODY TARGETING IL1RAP
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	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: 4
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	CAN04
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	Nadunolimab
D.3.9.2	Current sponsor code	CAN04
D.3.9.3	Other descriptive name	FULLY HUMANIZED LOW FUCOSE IGG1Κ MONOCLONAL ANTIBODY TARGETING IL1RAP
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	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

Advanced solid tumors

Tumores sólidos avanzados

E.1.1.1

Medical condition in easily understood language

Phase 1: Any type of locally advanced or metastatic cancer who have no therapeutic alternatives;
Phase 2: Locally advanced or metastatic colorectal cancer (mCRC), NSCLC, or biliary tract cancer (BTC)

Fase 1: cualquier tipo de cancer localmente avanzado que no tenga alternativas terapéuticas;
Fase 2: cáncer colorrectal localmente avanzado o metastásico (CCRm), CPNM o cáncer de vías biliares (CVB)

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10052362
E.1.2	Term	Metastatic colorectal cancer
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.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10055111
E.1.2	Term	Biliary cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase 1: To assess the safety and tolerability of CAN04 in combination with selected standard chemotherapy regimens and to establish MTD and/or RP2D.
Phase 2: To assess the preliminary efficacy of CAN04 in combination with chemotherapy regimens measured as tumour response.

Fase 1: Evaluar la seguridad y la tolerabilidad de CAN04 en combinación con determinadas pautas de quimioterapia de referencia y establecer la DMT y/o la DRF2.
Fase 2: Evaluar la eficacia preliminar de CAN04 en combinación con pautas de quimioterapia determinada mediante la respuesta tumoral

E.2.2

Secondary objectives of the trial

Phase 1
Efficacy: To assess preliminary anti-tumour activity of CAN04 in combination with selected standard chemotherapy regimens.
PK: To characterize the PK profiles of CAN04 after a single dose and at steady state after multiple doses in combination with chemotherapy using a population PK analysis approach.

Phase 2
Safety: To further characterise the safety and tolerability of CAN04 in combination with chemotherapy at the MTD/RP2D.
Efficacy: To assess the preliminary efficacy of CAN04 in combination with chemotherapy regimens measured as additional tumour response, time-to-event endpoints, and change in serum biomarkers.
PK: To characterise the PK profiles of CAN04 after a single dose and at steady state after multiple doses in combination with chemotherapy using a population PK analysis approach.

Fase 1
Eficacia: Evaluar la actividad antitumoral preliminar de CAN04 en combinación con determinadas pautas de quimioterapia de referencia.
FC: Caracterizar los perfiles farmacocinéticos de CAN04 después de una dosis única y en equilibrio después de dosis múltiples en combinación con quimioterapia utilizando un método de análisis FC poblacional.

Fase 2
Seguridad: Definir mejor la seguridad y la tolerabilidad de CAN04 en combinación con quimioterapia en la DMT/DRF2.
Eficacia: Evaluar la eficacia preliminar de CAN04 en combinación con pautas de quimioterapia determinada mediante la respuesta tumoral adicional, criterios de valoración del tiempo hasta el episodio y variación de biomarcadores séricos.
FC: Caracterizar los perfiles FC de CAN04 después de una dosis única y en equilibrio después de dosis múltiples en combinación con quimioterapia utilizando un método de análisis FC poblacional.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

General:
1. Subjects of age
2. ECOG 0-1

Phase I:
1. Subject has histologically or cytologically confirmed diagnosis of locally advanced cancer or metastatic cancer.
2. Subject has a condition where all standard therapeutic options with proven survival benefit have been exhausted, refused by the subject, or are contraindicated. OR Subject has a condition where 1 of the 3 study regimens (mFOLFOX, DTX, or G/C) is considered SoC for the next-line treatment.

Phase II:
1. Subject must have at least 1 measurable lesion as defined by RECIST v1.1.
2. Subjects with histologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of rectum or colon, squamous or non-squamous unresectable stage IIIB or stage IV NSCLC, or non-resectable, recurrent, or metastatic biliay tract cancer amenable for G/C treatment

For a complete list of inclusion criteria, please refer to Protocol, section 4.1.1 Inclusion Criteria

General:
1. Sujeto >= 18 años de edad
2. ECOG 0-1

Fase I:
1. El sujeto debe tener un diagnóstico confirmado histológica o citológicamente de cáncer localmente avanzado o metastásico.
2. El sujeto padece un trastorno para el que se han agotado todas las opciones terapéuticas habituales con un beneficio demostrado en la supervivencia, el sujeto las rechaza o están contraindicadas. O el sujeto padece una enfermedad en la que 1 de las 3 pautas del estudio (mFOLFOX, DTX o G/C) se considera el tratamiento de referencia para la siguiente línea.

Fase II:
1. El sujeto debe tener al menos 1 lesión medible según los criterios RECIST v1.1.
2. El sujeto tiene un diagnóstico confirmado histológica o citológicamente, de adenocarcinoma de colon o recto metastásico o localmente avanzado, un CPNM epidermoide o no epidermoide en estadio IIIB o IV irresecable, o carcinoma de vías biliares irresecable, recurrente o metastásico, tributario de tratamiento con G/C

Para ver la lista completa de criterios de inclusión, referirse al protocolo, sección 4.1.1 Criterios de Inclusión

E.4

Principal exclusion criteria

General Study Exclusion Criteria:
1. Subject has a known or suspected allergy to study drugs (including chemotherapy regimens), any of its components.
2. Subject has another histologically confirmed cancer different from those described in inclusion criteria, except for cervical carcinoma in situ,
superficial non-invasive bladder tumour, curatively treated stage I non-melanoma skin cancer, or prostate cancer subjects curatively treated with surgery or radiation and not receiving systemic or androgen deprivation therapy.
3. Subject has uncontrolled or significant heart failure defined as New York Heart Association Classification III or IV.
4. Subjects to receive mFOLFOX or DTX: having peripheral sensory neuropathy Grade ≥2.
5. Subject has QT interval corrected using Fridericia’s formula (QTcF) >480 msec at screening.
6. Subjects to receive DTX and CAN04: if they have liver metastases and aspartate aminotransferase (AST) and/or ALT >1.5 × upper limit of normal (ULN) concomitant with alkaline phosphatase >2.5 × ULN.
7. Subject has uncontrolled brain metastases. Subjects are allowed to be enrolled if brain metastasis has been previously treated with surgery, and/or stereotactic radiosurgery and are considered controlled (controlled by the dose ≤10 mg/day of prednisone or equivalent) at the time of the first dose of CAN04. For asymptomatic subjects, brain imaging during screening is not required.
8. Subject has an active severe infection requiring parenteral antibiotics at the time of enrolment or subjects currently receiving oral antibiotics as a continuation of a previous course of parenteral antibiotics. Subjects can be enrolled when antibiotic treatment is complete and if there are no signs of residual infection.
9. Subject has a history of autoimmune disease requiring systemic immunosuppressive therapy (daily prednisone equivalent doses >10 mg/day).
10. Subject is expected to require any other form of systemic or localised anti-neoplastic therapy while on study (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
11. Subject has had an allogeneic tissue/solid organ transplant.

For a complete list of exclusion criteria, including Dose Escalation Phase (Phase 1) and Phase 2 please refer to Protocol, section 4.1.2 Study Exclusion Criteria

Criterios de exclusión del estudio generales:
1. El sujeto tiene alergia conocida o sospecha de alergia a los fármacos del estudio (incluyendo los regímenes de quimioterápia), a cualquiera de sus componentes
2. El sujeto tiene otro cáncer confirmado histológicamente diferente de los descritos en los criterios de inclusión, excepto carcinoma cervicouterino in situ, tumor vesical superficial no invasivo, cáncer de piel distinto del melanoma en estadio I tratado con intención curativa o cáncer de próstata tratado con intención curativa con cirugía o radioterapia y no recibe tratamiento sistémico o de privación androgénica.
3. El sujeto tiene una insuficiencia cardiaca no controlada o significativa, definida por la Clasificación de la Asociación del Corazón de Nueva York como III o IV
4. Sujetos que vayan a recibir mFOLFOX o DTX: presencia de neuropatía sensitiva periférica de grado ≥2
5. Sujetos que en la selección tenga un intervalo de QT corregida utilizado la fórmula de Friderica (QTcF) >480 msec
6. Sujetos que vayan a recibir DTX y CAN04: si las metástasis hepáticas y valores de aspartato aminotransferasa (AST) y/o ALT >1,5 veces el límite superior de la normalidad (LSN) concomitantes con valores de fosfatasa alcalina >2,5 x LSN
7. El sujeto tiene metástasis cerebrales no controladas. Se permite la inclusión de estos sujetos si las metástasis cerebrales se han tratado previamente con cirugía y/o radiocirugía estereotáctica y se considera que están controladas (controladas con la dosis ≤10 mg/día de prednisona o equivalente) en el momento de la Primera dosis de CAN04. Para sujetos asintomáticos, no se requiere imágenes cerebrales durante la selección.
8. El sujeto tiene una infección activa grave que requiere antibióticos parenterales en el momento de la inclusión o los sujetos que actualmente reciben antibióticos orales como continuación de un curso anterior de antibióticos parenterales. Los sujetos pueden ser incluidos cuando se complete el tratamiento con antibióticos y si no hay signos de infección residual.
9. El sujeto tiene antecedentes de enfermedad autoinmunitaria que requiere tratamiento inmunodepresor sistémico (dosis diaria equivalente de prednisona >10 mg/día)
10. Se prevé que el sujeto va a necesitar cualquier otra forma de tratamiento antineoplásico sistémico o localizado durante el estudio (incluido el tratamiento de mantenimiento con otro fármaco, radioterapia y/o resección quirúrgica)
11. El sujeto ha recibido un alotrasplante de tejidos u órgano sólido.

Para ver la lista completa de criterios de exclusión, incluyendo la Fase de Escalado de Dosis (Fase 1) y la Fase 2, referirse al protocolo, sección 4.1.2 Criterios de exclusión

E.5 End points

E.5.1

Primary end point(s)

Phase 1
• Nature, grade, and frequency of DLTs
• Frequency, duration, and severity (according to CTCAE v5.0) of AEs
• Changes in vital signs, serum chemistry, and haematology
• Treatment modifications measured as a percentage of relative dose intensity
• Percentage of subjects discontinued from all or part of study treatment and reasons for discontinuations

Phase 2
ORR defined as the percentage of subjects with PR or CR based on RECIST v1.1

Fase 1
- Naturaleza, grado y frecuencia de TLD.
- Frecuencia, duración e intensidad (según los CTCAE v5.0) de los acontecimientos adversos (AA).
- Variaciones de las constantes vitales, la bioquímica sérica y la hematología.
- Modificaciones del tratamiento expresadas en porcentaje de la intensidad relativa de la dosis.
- Porcentaje de sujetos que suspenden el tratamiento del estudio de manera total o parcial y motivos de la suspensión.

Fase 2
TRG, definida como el porcentaje de sujetos con respuesta parcial (RP) o respuesta completa (RC) conforme a los criterios RECIST v1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

Throughout the study

A lo largo del estudio

E.5.2

Secondary end point(s)

Phase 1
Efficacy:
• ORR defined as the percentage of subjects with PR or CR based on RECIST v1.1
• iORR defined as the percentage of subjects with iPR or iCR based on iRECIST
• PFS per RECIST v1.1, measured from the start of study treatment until disease progression or death from any cause
• iPFS by iRECIST
• DCR measured as a percentage of subjects with CR + PR + SD ≥16 weeks
• iDCR measured as a percentage of subjects with iCR + iPR + iUPD/iSD ≥16 weeks
• DOR defined as the time from response to progression/death
• Change from baseline upon treatment in serum biomarkers: CEA and CA19-9 (CEA for subjects with CRC; CEA and CA19-9 for subjects with BTC)
• Changes from baseline upon treatment in ECOG PS and body weight

PK:
• Serum PK parameters of CAN04 and potential covariates that impact the PK parameters

Phase 2
Safety:
• Frequency, duration, and severity (according to CTCAE v5.0) of AEs
• Changes in vital signs, serum chemistry, and haematology
• Treatment modifications measured as a percentage of relative dose intensity
• Percentage of subjects discontinued from all or part of study treatment and respective reason for discontinuation

Efficacy:
• iORR defined as the percentage of subjects with iPR or iCR based on iRECIST
• PFS per RECIST v1.1, measured from the start of study treatment until disease progression or death from any cause
• iPFS per iRECIST
• OS measured from the start of treatment until death from any cause
• DCR measured as a percentage of subjects with CR + PR + SD ≥16 weeks
• iDCR measured as a percentage of subjects with iCR + iPR + iUPD/iSD ≥16weeks
• DOR defined as the time from response to progression or death
• Change from baseline upon treatment in serum biomarkers: CEA and CA19-9 (CEA for subjects with CRC. CEA and CA19-9 for subjects with BTC)
• Changes from baseline upon treatment in ECOG PS and body weight

PK:
• Serum PK parameters of CAN04 and potential covariates that impact the PK parameters

Fase 1
Eficacia:
•TRG, definida como el porcentaje de sujetos con RP o RC conforme a los criterios RECIST 1.1.
•iTRG, definida como el porcentaje de pacientes con iRP o iRC conforme a los criterios iRECIST
•SLP, medida desde el comienzo del tratamiento del estudio hasta la progresión de la enfermedad o la muerte por cualquier causa;
•iSLP según iRECIST
•TCE medida como el porcentaje de sujetos con RC + RP + EE ≥16 semanas
• iTCE medida como el porcentaje de sujetos con iRC + iRP + iPES/ iEE ≥16 semanas
•DR definido como el tiempo desde la respuesta a la progresión/ muerte
•Variación con respecto al momento basal de los biomarcadores séricos: CEA y CA 19-9 (CEA para sujetos con CCR ; CEA y CA19-9 para sujetos con CVB)
•Variaciones del EF del ECOG y el peso corporal durante el tratamiento con respecto al momento basal

FC:
Parámetros FC séricos de CAN04 y posibles covariables que influyen en los parámetros FC

Fase 2
Seguridad:
Frecuencia, duración e intensidad (según Clos TCAE v5.0) de AA
Variaciones de las constantes vitales, la bioquímica sérica y la hematología;
Modificaciones del tratamiento expresadas en porcentaje de la intensidad relativa de la dosis,
Porcentaje de sujetos que suspendan el tratamiento del estudio de manera total o parcial y el correspondiente motivo de la suspensión.

Eficacia:
•iTRG, definida como el porcentaje de pacientes con iRP o iRC conforme a los criterios iRECIST
•SLP según RECIST v1.1, medida desde el comienzo del tratamiento del estudio hasta la progresión de la enfermedad o la muerte por cualquier causa;
•iSLP según iRECIST
SG medida desde el inicio del tratamiento hasta la muerte por cualquier causa
•TCE medida como el porcentaje de sujetos con RC + RP + EE ≥16 semanas
• iTCE medida como el porcentaje de sujetos con iRC + iRP + iPES/ iEE ≥16 semanas
•DR definido como el tiempo desde la respuesta a la progresión/ muerte
•Variación con respecto al momento basal de los biomarcadores séricos: CEA y CA 19-9 (CEA para sujetos con CCR ; CEA y CA19-9 para sujetos con CVB)
•Variaciones del EF del ECOG y el peso corporal durante el tratamiento con respecto al momento basal

FC:
Parámetros FC séricos de CAN04 y posibles covariables que influyen en los parámetros FC

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the study

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

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarkers: To assess disease-related, genetic, inflammatory, immune, or microenvironment-related parameters related to CAN04, in the circulation and in tumour tissue.
Immunogenicity: To assess ADA formation against CAN04.

Biomarcadores: para evaluar parametros relacionados con la enfermedad, genéticos, inflamatorios, inmunitarios o relacionados con el microambiente relacionados con CAN04 en la circulación y en el tejido tumoral.
Inmunogenicidad: evaluación de la formación de AAF contra CAN04

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 study.

Estudio de 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

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

CAN04 en combinación con 3 SoC

CAN04 in combination with 3 SoC

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

Israel

Belgium

France

Latvia

Lithuania

Poland

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 the study is defined as the date on which the last subject completes the last visit of Phase 2 of the study.

Se define el final del estudio como la fecha en la que el último sujeto completa la última visita de la Fase 2 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:

140

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

140

F.4.2.2

In the whole clinical trial

165

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 is responsible for ensuring that consideration has been given to the post-study care of the subject’s medical condition. Post-study treatment (including continued chemotherapy administration after CAN04 discontinuation) is not provided or reimbursed as part of this study. Only the post-study treatment given immediately after CAN04 discontinuation will be collected in the eCRF.

El investigador es responsable de garantizar que se haya tenido en cuenta la atención posterior al estudio de la condición médica del sujeto. El tratamiento después del estudio (incluyendo la
administración continuada de quimioterápia después de suspender CAN04) no será proporcionada o reembolsada como parte de este estudio. Solamente el tratamiento después del estudio inmediatamente después de la interrupción de CAN04 se recogerán en el eCRD.

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

2021-09-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-08-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-06-23

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