Clinical Trials Register

Summary
EudraCT Number:	2021-004807-42
Sponsor's Protocol Code Number:	CA116-001
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-11-18
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2021-004807-42

A.3

Full title of the trial

A Phase 2 Open-label Randomized Study of Farletuzumab Ecteribulin (MORAb-202), a Folate Receptor Alpha-targeting Antibody-Drug Conjugate, versus Investigator's Choice Chemotherapy in Women with Platinum-resistant High-grade Serous (HGS) Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Studio di fase 2 randomizzato in aperto su farletuzumab ecteribulin (MORAb-202), un coniugato anticorpo-farmaco mirato al recettore alfa del folato rispetto alla chemioterapia a scelta dallo sperimentatore in donne affette da carcinoma ovarico, peritoneale primario o delle tube di Falloppio di alto grado resistente al platino (HGS)

A.3.1

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

A Phase 2 Study of MORAb-202 in Platinum-resistant High-grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Studio di fase 2 su MORAb-202 nel carcinoma ovarico sieroso di alto grado, peritoneale primario o delle tube di Falloppio resistente al platino

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CA116-001

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1269-0669

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	BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
B.1.3.4	Country	Belgium
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	Bristol-Myers Squibb International Corporation Belgium
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	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	Head of the GSM-CT
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine - l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.6	E-mail	clinical.trials@bms.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Topotecan
D.2.1.1.2	Name of the Marketing Authorisation holder	medac
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	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	TOPOTECAN
D.3.9.1	CAS number	123948-87-8
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB11191MIG
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	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Paclitaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Bendalis GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Paclitaxel
D.3.2	Product code	[-]
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	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB09583MIG
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	6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.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	MORAb-202
D.3.2	Product code	[BMS-986445]
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	Farletuzumab ecteribulin
D.3.9.2	Current sponsor code	BMS-986445
D.3.9.4	EV Substance Code	SUB215766
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	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.IMP: 4
D.1.2 and D.1.3	IMP Role	Comparator
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	Pegylated Liposomal Doxorubicin
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxter Holding 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	Pegylated Liposomal Doxorubicin
D.3.2	Product code	[-]
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	Doxorubicin
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	doxorubicin, liposomal, pegylated
D.3.9.4	EV Substance Code	SUB33393
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	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
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	MORAb-202
D.3.2	Product code	[BMS-986445]
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	Farletuzumab ecteribulin
D.3.9.2	Current sponsor code	BMS-986445
D.3.9.4	EV Substance Code	SUB215766
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	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.IMP: 6
D.1.2 and D.1.3	IMP Role	Comparator
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	Topotecan
D.2.1.1.2	Name of the Marketing Authorisation holder	medac
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	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	TOPOTECAN
D.3.9.1	CAS number	123948-87-8
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB11191MIG
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	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Platinum-resistant High-grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Carcinoma ovarico, peritoneale primario o delle tube di Falloppio di alto grado resistente al platino

E.1.1.1

Medical condition in easily understood language

Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer

tumore ovarico, peritoneale primario o delle tube di Falloppio

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	PT
E.1.2	Classification code	10033128
E.1.2	Term	Ovarian 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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10016180
E.1.2	Term	Fallopian tube 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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10052171
E.1.2	Term	Peritoneal carcinoma
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

1. To compare objective response rate of MORAb-202 vs Investigator's Choice (IC) chemotherapy (in all randomized participants)
2. To evaluate the proportion of participants with treatment-related adverse events (TRAEs) leading to discontinuation in each arm within 6 months from first dose of study drug administration in all treated
participants

1. Confrontare il tasso di risposta obiettiva (ORR) di MORAb-202 rispetto alla chemioterapia IC (in tutti le partecipanti randomizzate)
2. Valutare la percentuale di partecipanti con eventi avversi correlati al trattamento (TRAE) che portano all’interruzione in ciascun braccio entro 6 mesi dalla somministrazione della prima dose del farmaco dello studio in tutte le partecipanti trattate

E.2.2

Secondary objectives of the trial

1. To evaluate Disease Control Rate (DCR) of MORAb-202 and IC chemotherapy in all randomized participants
2. To evaluate Duration of Response (DoR) of MORAb-202 and IC chemotherapy in all randomized participants
3. To evaluate Progression-Free Survival (PFS) of MORAb-202 and IC chemotherapy in all randomized participants

1. Valutare il tasso di controllo della malattia (DCR) di MORAb-202 e la chemioterapia IC in tutte le partecipanti randomizzate
2. Valutare la durata della risposta (DoR) di MORAb-202 e la chemioterapia IC in tutte le partecipanti randomizzate
3. Valutare la sopravvivenza libera da progressione (PFS) di MORAb-202 e la chemioterapia IC in tutte le partecipanti randomizzate

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Participants must be 18 years old or local age of majority at the time of signing the informed consent
2) Female participants with histologically confirmed diagnosis of HGS ovarian, primary peritoneal, or fallopian tube cancer.
3) Platinum-resistant disease, defined as:
- For participants who had only 1 line of platinum-based therapy: progression between > 1 month and <= 6 months after the last dose of platinum-based therapy of at least 4 cycles.
- For participants who had 2 or 3 lines of platinum-based therapy: progression <= 6 months after the last dose of platinum-based therapy.
4) Participants have received at least 1 but no more than 3 prior lines of systemic therapy and for whom single-agent therapy is appropriate as the next line of therapy. Participants may have been treated with up to 1 line of therapy subsequent to determination of platinum-resistance.
- Participants must have received prior treatment with bevacizumab or must be deemed medically inappropriate or ineligible/intolerant to receive bevacizumab, refused to receive bevacizumab, or been unable to receive bevacizumab due to lack of access.
NOTES:
Neoadjuvant ± adjuvant chemotherapy will be considered 1 line of therapy.
Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered part of the preceding line of therapy.
Therapy changed in the absence of progression will be considered part of the same line.
5) Disease progression per RECIST v1.1 (by Investigator assessment) of at least 1 measurable lesion on or after the most recent therapy.
6) Either formalin-fixed, paraffin-embedded (FFPE) tissue or newly-obtained biopsies must be available for FRa assessment prior to randomization.
7) Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

1. La partecipante deve avere un’età =18 anni o maggiorenne a seconda di dove si svolge lo studio al momento della firma del modulo di consenso informato
2. Partecipanti di sesso femminile con diagnosi istologicamente confermata di carcinoma ovarico HGS, peritoneale primario o delle tube di Falloppio
3. Malattia resistente al platino, definita come:
- Per le partecipanti che hanno ricevuto solo 1 linea di terapia a base di platino: progressione tra >1 mese e <= 6 mesi dopo l’ultima dose di terapia a base di platino di almeno 4 cicli.
- Per le partecipanti che hanno ricevuto 2 o 3 linee di terapia a base di platino: progressione in <=6 mesi dopo l’ultima dose di terapia a base di platino.
4. Le partecipanti hanno ricevuto almeno 1 ma non più di 3 linee precedenti di terapia sistemica, per le quali la terapia con singolo agente è appropriata come linea di terapia successiva. Le partecipanti possono essere state trattate con massimo 1 linea di terapia successiva alla determinazione di resistenza al platino.
- Le partecipanti devono aver ricevuto un precedente trattamento con bevacizumab o essere ritenute clinicamente inappropriate o non idonee/intolleranti a ricevere bevacizumab, aver rifiutato di ricevere bevacizumab o non aver potuto ricevere bevacizumab per mancanza di accesso.
NOTE:
La chemioterapia neoadiuvante ± adiuvante sarà considerata 1 linea di terapia.
La terapia di mantenimento (ad es., bevacizumab, inibitori della poli [adenosina disfosfato-ribosio] polimerasi [PARP]) sarà considerata parte della linea di terapia precedente.
La terapia modificata in assenza di progressione sarà considerata parte della medesima linea.
5. Progressione della malattia secondo i criteri RECIST v1.1 (in base alla valutazione dello sperimentatore) di almeno 1 lesione misurabile durante o dopo la terapia più recente.
6. Prima della randomizzazione, deve essere disponibile del tessuto fissato in formalina e incluso in paraffina o biopsie recentemente ottenute per la valutazione dell’FRa.
7. Stato di validità secondo l’Eastern Cooperative Oncology Group [Gruppo orientale cooperativo di oncologia] pari a 0 oppure 1.

E.4

Principal exclusion criteria

- Clear cell, mucinous, endometrioid or sarcomatous histology, or mixed tumors containing components of any of these histologies, or low grade or borderline ovarian cancer
- Primary platinum-refractory ovarian cancer defined as disease progression within 1 month of the last dose of the first line platinum-containing regimen.
- Pulmonary function test (PFT) abnormalities
- Investigator-assessed current ILD/pneumonitis, or ILD/pneumonitis suspected at Screening or history of ILD/pneumonitis of any severity including ILD/pneumonitis from prior anti-cancer therapy.
- Recent chest radiotherapy received under 6 months before starting study treatment
- Any autoimmune, connective tissue, or inflammatory disorders where there is documented (or suspicion of) pulmonary involvement
- Uncontrolled or significant cardiovascular conditions within 6 months prior
- Uncontrolled medical disorders that, in the opinion of the Investigator or Sponsor, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results
- Prior treatment with an investigational FRa-targeting agent and FRa-targeting ADC
- Evidence of organ dysfunction or any clinically-significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population
- Inadequate liver function evidenced by abnormal levels of total bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) or serum albumin
- Has any prior severe hypersensitivity (>= Grade 3) to monoclonal antibodies or eribulin or contraindication to the receipt of corticosteroids or any of the excipients
- History of allergy or contraindication to IC chemotherapy agent selected if randomized to Arm C
- Participants currently in other interventional trials may not participate in BMS clinical trials until the protocol specific washout period is achieved

- Istologia endometrioide, a cellule chiare, mucinosa o sarcomatosa o tumori misti contenenti componenti di una di queste istologie o carcinoma ovarico di basso grado o borderline.
- Carcinoma ovarico primario refrattario al platino, definito come progressione della malattia entro 1 mese dall’ultima dose del regime contenente platino di prima linea
- Anomalie ai test di funzionalità polmonare: FEV1 <70% o FVC <60% e DLCO <80%.
- ILD/polmonite in corso valutata dallo sperimentatore o ILD/polmonite sospettata allo screening o anamnesi di ILD/polmonite di qualsiasi gravità, compresa l’ILD/polmonite da precedente terapia antitumorale
- Recente radioterapia del torace ricevuta nei 6 mesi precedenti l'inizio del trattamento di studio
- Qualsiasi disturbo autoimmune, del tessuto connettivo o infiammatorio (ad es. artrite reumatoide, sindrome di Sjögren, sarcoidosi, ecc.) con coinvolgimento polmonare documentato (o sospetto).
- Condizioni cardiovascolari incontrollate o significative nei 6 mesi precedenti
- Disturbi medici non controllati che, a giudizio dello sperimentatore o dello sponsor, possono aumentare il rischio associato alla partecipazione allo studio o alla somministrazione del farmaco in studio, compromettere la capacità del partecipante di ricevere la terapia del protocollo o interferire con l'interpretazione dei risultati dello studio
- Trattamento precedente con un agente bersaglio FRa sperimentale e ADC mirato a FRa
- Evidenza di disfunzione d'organo o qualsiasi deviazione clinicamente significativa dalla norma nell'esame obiettivo, nei segni vitali, nell'ECG o nelle determinazioni cliniche di laboratorio oltre ciò che è coerente con la popolazione target
- Funzionalità epatica inadeguata evidenziata da livelli anormali di bilirubina totale, fosfatasi alcalina (ALP), alanina aminotransferasi (ALT) e aspartato aminotransferasi (AST) o albumina sierica
- Presenta una precedente grave ipersensibilità (>= Grado 3) agli anticorpi monoclonali o all'eribulina o controindicazioni alla somministrazione di corticosteroidi o di uno qualsiasi degli eccipienti
- Storia di allergia o controindicazione all'agente chemioterapico IC selezionato se randomizzato al braccio C
- I partecipanti attualmente ad altri studi interventistici non possono partecipare agli studi clinici sulla BMS fino al raggiungimento del periodo di washout specifico del protocollo

E.5 End points

E.5.1

Primary end point(s)

1. Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per Investigator assessment
2. Occurence of TRAEs leading to discontinuation.

1. Tasso di risposta obiettiva (ORR) in base ai criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1, secondo la valutazione dello sperimentatore
2. Eventi avversi correlati al trattamento (TRAE) che portano all’interruzione

E.5.1.1

Timepoint(s) of evaluation of this end point

1 and 2: up to 2 years

1 e 2: fino a 2 anni

E.5.2

Secondary end point(s)

1. Occurrence of the AEs/SAEs, treatment-related AEs/SAEs, AEs leading
to discontinuation, AESIs, deaths and laboratory abnormalities
2. DoR by RECIST v1.1 per investigator Assessment among responders
3. PFS by RECIST v1.1 per Investigator Assessment
4. DCR by RECIST v1.1 per Investigator Assessment

1. Incidenza e gravità degli eventi avversi (EA)/eventi avversi seri (SAE), EA che portano all’interruzione del trattamento, EA/SAE correlati al trattamento che portano all’interruzione del trattamento, EA di particolare interesse (AESI), decessi e anomalie di laboratorio
2. DoR secondo RECIST v1.1 in base alla valutazione dello sperimentatore tra i responder
3. PFS secondo RECIST v1.1 in base alla valutazione dello sperimentatore
4. DCR secondo RECIST v1.1 in base alla valutazione dello sperimentatore

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 2, 3 and 4: up to 2 years

1, 2, 3 e 4: fino a 2 anni

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

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

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Chile

Japan

United States

France

Spain

Italy

Belgium

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 the last participant's last visit

La fine della sperimentazione corrisponde all'ultima visita dell'ultima partecipante

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

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

150

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)

Continuous safety and tumor assessment evaluation will guide the decision to treat a participant with additional cycles of study therapy beyond 2 years, if the participant has a confirmed clinical benefit.

La valutazione continua della sicurezza e della valutazione del tumore guiderà la decisione di trattare una partecipante con cicli aggiuntivi di terapia in studio oltre i 2 anni, se la partecipante ha un beneficio clinico confermato.

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

2023-01-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-11-23

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

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