Clinical Trials Register

Summary
EudraCT Number:	2018-001534-17
Sponsor's Protocol Code Number:	MS201943-0029
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-02-17
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-001534-17

A.3

Full title of the trial

A Phase Ib Safety Run-in and Randomized Phase II, Open-label Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of M6620 in Combination with Avelumab and Carboplatin in Comparison to Standard of Care Therapy in Participants with PARPi-resistant Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer.

Studio in aperto con una fase Ib di run-in di sicurezza e una fase II randomizzata per valutare l’efficacia, la sicurezza, la tollerabilità e la farmacocinetica di M6620 in combinazione con avelumab e carboplatino rispetto alla terapia standard in partecipanti con carcinoma ovarico ricorrente, carcinoma peritoneale primitivo o carcinoma delle tube di Falloppio resistenti ai PARPi

A.3.1

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

M6620 in Combination with Avelumab and Carboplatin versus standard chemotherapy in Subjects with PARPi-resistant Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer.

M6620 in combinazione con avelumab e carboplatino rispetto alla terapia standard in partecipanti con carcinoma ovarico ricorrente, carcinoma peritoneale primitivo o carcinoma delle tube di Falloppio resistenti ai PARPi

A.3.2

Name or abbreviated title of the trial where available

Phase Ib/II Study of Carboplatin+M6620+ Avelumab in PARPi-resistant Ovarian Cancer

Studio di fase Ib/II su carboplatino + M6620 + avelumab nel carcinoma ovarico resistente ai PARPi

A.4.1

Sponsor's protocol code number

MS201943-0029

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	MERCK KGAA
B.1.3.4	Country	Germany
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	Merck KGaA
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck KGaA
B.5.2	Functional name of contact point	Communication Centre Merck KGaA
B.5.3	Address:
B.5.3.1	Street Address	Frankfurter Strasse 250
B.5.3.2	Town/ city	Darmstadt
B.5.3.3	Post code	64293
B.5.3.4	Country	Germany
B.5.4	Telephone number	+496151725200
B.5.5	Fax number	+496151722000
B.5.6	E-mail	service@merckgroup.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	Yes
D.2.1.1.1	Trade name	Bavencio
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Europe 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	Avelumab
D.3.2	Product code	[MSB0010718C]
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	Avelumab
D.3.9.2	Current sponsor code	Avelumab
D.3.9.4	EV Substance Code	SUB180078
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	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: 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	.
D.3.2	Product code	[M6620]
D.3.4	Pharmaceutical form	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.3.9.2	Current sponsor code	M6620
D.3.9.4	EV Substance Code	SUB193628
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	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	Yes
D.2.1.1.1	Trade name	Carboplatin
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	Carboplatino
D.3.2	Product code	[.]
D.3.4	Pharmaceutical form	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	Carboplatino
D.3.9.1	CAS number	41575-94-4
D.3.9.2	Current sponsor code	.
D.3.9.4	EV Substance Code	SUB06614MIG
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	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: 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	Paclitaxel
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 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: 5
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	Avastin 25 mg/ml concentrate for solution for infusion.
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH (EU/1/04/300/001)
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	Avastin
D.3.2	Product code	[.]
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	Bevacizumab
D.3.9.1	CAS number	216974-75-3
D.3.9.2	Current sponsor code	.
D.3.9.4	EV Substance Code	SUB16402MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	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	Gemzar - Gemcitabine
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	.
D.3.2	Product code	[.]
D.3.4	Pharmaceutical form	Powder 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	Gemcitabina
D.3.9.1	CAS number	95058-81-4
D.3.9.2	Current sponsor code	.
D.3.9.4	EV Substance Code	SUB02324MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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: 7
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	Caelyx
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
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	Caelyx 2 mg/ml concentrate for solution for infusion
D.3.2	Product code	[.]
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	DOXORUBICIN
D.3.9.2	Current sponsor code	.
D.3.9.4	EV Substance Code	SUB126795
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.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

PARPi-resistant Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

carcinoma ovarico ricorrente, carcinoma peritoneale primitivo o carcinoma delle tube
di Falloppio resistenti ai PARPi

E.1.1.1

Medical condition in easily understood language

Gynaecologic cancers

Tumori ginecologici

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	10038977
E.1.2	Term	Retroperitoneal 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.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part A: To evaluate a safe, tolerable RP2D of carboplatin + M6620 in combination with avelumab in participants with PARPi-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer.
Part B: To evaluate antitumor activity of carboplatin + M6620 in combination with avelumab compared with the standard of care treatment in participants with PARPi-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer.

Parte A: Valutare una RP2D sicura e tollerabile di carboplatino + M6620 in combinazione con avelumab in partecipanti con carcinoma ovarico ricorrente, carcinoma peritoneale primitivo o carcinoma delle tube di Falloppio resistenti ai PARPi.
Parte B: l’attività antitumorale di carboplatino + M6620 in combinazione con avelumab rispetto alla terapia standard in partecipanti con carcinoma ovarico ricorrente, carcinoma peritoneale primitivo o carcinoma delle tube di Falloppio resistenti ai PARPi.

E.2.2

Secondary objectives of the trial

Part A: To evaluate the safety and tolerability of carboplatin + M6620 at the RP2D when used in combination with avel in participants with PARPi-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer.
To evaluate the antitumor activity of carboplatin + M6620 at the RP2D in combination with avel in participants with PARPi-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer.
To characterize the pharmacokinetic (PK) profiles of avel and M6620 when given in combination with carbo.
Part B: To evaluate the safety and tolerability of carboplatin + M6620 at the RP2D in combination with avel.
To further evaluate antitumor activity of carbo + M6620 in combination with avelumab compared with the standard of care treatment.
To characterize the PK of avel and M6620 when given in combination with carboplatin.
To characterize the immunogenicity of avel in combination with M6620+carbo.

Part A: la sicur e la tollerab di carboplatino + M6620 alla RP2D in combinaz con avelumab in partecip con carcin ovarico ricorr, carcin peritoneale primit o carcin delle tube di Falloppio resist ai PARPi
Valutare l’attiv antitum di carboplatino + M6620 alla RP2D in combinaz con avelumab in partecip con carcin ovarico ricorr, carcin peritoneale primit o carcin delle tube di Falloppio resist ai PARPi
Caratterizz i profili farmacocinetici (PK) di avelumab e M6620 quando somministr in combinaz con carboplatino
Part B: Valut la sicurez e la tollerab di carboplatino + M6620 alla RP2D in combinaz con avelumab in partecip con carcin ovarico ricorr, carcin peritoneale primit o carcin delle tube di Falloppio resist ai PARPi
Valut ulteriorm l’attiv antitum di carboplatino +M6620 in combinaz con avelumab rispetto alla terap standard
Caratterizz la PK di avelumab e M6620 quando somministr in combinaz con carboplatino
Caratterizz l’immunogenicità di avelumab in combinaz con M6620 + carboplatino

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female participants with recurrent epithelial ovarian cancer who have disease progression following maintenance treatment with a PARPi as defined below:
1.1 Participant must have histologically diagnosed epithelial ovarian, primary peritoneal, or fallopian tube cancer, with nonmucinous histology
1.2 Participants must have completed at least 2 previous courses of platinum containing therapy (eg, carboplatin or cisplatin) and had documented response (complete response [CR] or partial response [PR]) to the last platinum-based treatment prior to treatment with a PARPi
1.3 Participant has received the last dose of platinum-containing treatment at least 6 months prior to study enrollment
1.4 Participant has documented disease progression (radiological) after at least 4 months of maintenance treatment with PARPi following a response to platinum-based chemotherapy.
2. Confirmed BRCA 1/2 mutation status or agree to its testing on samples collected in the study.
3. Available formalin-fixed, paraffin-embedded (FFPE) tumor biopsies.
3.1 Part A: Optional – Two (2) paired on-treatment biopsies on Day 2 of Cycle 1 (first biopsy) and Day 2 of Cycle 1 or Cycle 2 (second biopsy), before and after M6620 administration, respectively, if assessed as feasible at low risk by the interventional radiologist.
3.2 Part B: Histological tissue specimen (tissue block or 8 to 10 unstained slides) must be available. An archival tumor biopsy is acceptable if obtained after the last progression on PARPi treatment and is less than 6 months old. Otherwise, participants must be willing to undergo mandatory biopsy during the Screening Period to obtain sufficient tissue for histological assessment. Participants need to have an attempted biopsy. However, participants who have measurable disease documented by a radiologist as not feasible or safe to be biopsied are eligible to enter the study.
4. Measurable disease according to RECIST v1.1.

1. Le partecipanti di sesso femminile con recidiva di carcinoma ovarico epiteliale che hanno manifestato una progressione di malattia dopo il trattamento di mantenimento con un PARPi come definito di seguito:
1.1 La partecipante deve presentare un carcinoma ovarico epiteliale, un carcinoma peritoneale primitivo o un carcinoma delle tube di Falloppio istologicamente diagnosticato e non mucinoso 1.2 Le partecipanti devono aver completato almeno 2 precedenti periodi di terapia a base di platino (ad es. carboplatino o cisplatino) e presentare una risposta documentata (risposta completa [CR] o risposta parziale [PR]) all’ultimo trattamento a base di platino prima del trattamento con un PARPi 1.3 La partecipante ha ricevuto l’ultima dose di trattamento contenente platino almeno 6 mesi prima dell’arruolamento nello studio
1.4 La partecipante ha una progressione della malattia documentata (radiologicamente) dopo almeno 4 mesi del trattamento di mantenimento con PARPi a seguito di una risposta alla chemioterapia a base di platino.
2. Stato di mutazione BRCA 1/2 confermato o consenso a effettuare tale test sui campioni raccolti durante lo studio.
3. Biopsie tumorali disponibili fissate in formalina e incluse in paraffina (FFPE).
3.1 Parte A: Opzionale – Due (2) coppie di biopsie prelevate durante il trattamento il Giorno 2 del Ciclo 1 (prima biopsia) e il Giorno 2 del Ciclo 1 o Ciclo 2 (seconda biopsia), prima e dopo la somministrazione di M6620, rispettivamente, se valutate fattibili a basso rischio da parte del radiologo interventista.
3.2 Parte B: Devono essere disponibili campioni di tessuto istologico (blocco di tessuto o da 8 a 10 vetrini non colorati). Una biopsia tumorale d’archivio è accettabile se ottenuta dopo l’ultima progressione durante il trattamento con PARPi e risale a meno di 6 mesi precedenti. In caso contrario, le partecipanti devono essere disposte a sottoporsi a una biopsia obbligatoria durante il periodo di screening per ottenere una quantità sufficiente di tessuto per la valutazione istologica. Le partecipanti devono sottoporsi a un tentativo di biopsia. Tuttavia, le partecipanti che presentano una malattia misurabile documentata da un radiologo come non fattibile o sicura per essere sottoposta a biopsia sono idonee a partecipare allo studio.
4. Malattia misurabile in base ai criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1.

E.4

Principal exclusion criteria

1. Treatment with a nonpermitted drug/intervention as listed below:
1.1. Concurrent anticancer treatment (e.g., cytoreductive therapy, radiotherapy, immune therapy, cytokine therapy, monoclonal antibody, or targeted small molecule therapy) or any study intervention within 4 weeks prior to start of study intervention, or not recovered from AEs related to such therapies
1.2. History of prior dose reductions or dose interruptions while receiving cisplatin or carboplatin due to toxicity from the platinum or intolerance to either agent, unless discussed with and approved by the Sponsor Medical Monitor
1.3. Prior treatment with a PD-1/PD-L1 targeting agent
2. Current use of the following medications at the time of enrollment:
2.1. Immunotherapy or immunosuppressive drugs at the time of enrollment (e.g., chemotherapy or systemic corticosteroids) EXCEPT for (a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra articular injection), (2) systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent, (3) steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
2.2. Growth factors EXCEPT where indicated for treatment of study intervention related myelosuppression and for prophylaxis of repeat myelosuppression after initial occurrence
2.3. Herbal remedies with immunostimulating properties (e.g., mistletoe extract) or known to potentially interfere with major organ function (e.g., hypericin)
2.4. Other DNA damage repair inhibitors (except PARPi) (e.g., inhibitors of ATR, ataxia telangiectasia mutated [ATM] kinase, DNA-dependent protein kinase [DNA-PK], or Wee kinases).

1. Terapia concomitante con un farmaco/intervento non permesso come elencato di seguito:
1.1. Trattamento antitumorale concomitante (ad esempio, terapia citoriduttiva, radioterapia, immunoterapia, terapia a base di citochine, anticorpi monoclonali o terapia mirata con piccole molecole) o qualsiasi intervento dello studio entro 4 settimane prima dell’avvio dell’intervento dello studio, o mancata ripresa da EA correlati a tali terapie
1.2. Anamnesi di precedenti riduzioni della dose o interruzioni della dose durante il trattamento con cisplatino o carboplatino a causa di tossicità correlata al platino o intolleranza a qualsiasi agente, a meno che non discusso e approvato dal responsabile del monitoraggio medico dello sponsor
1.3. Precedente trattamento con un agente che agisce contro PD-1/PD-L1
2. Attuale uso dei seguenti farmaci al momento dell’arruolamento:
2.1. Farmaci immunoterapici o immunosoppressivi al momento dell’arruolamento (ad esempio, chemioterapici o corticosteroidi sistemici), ESCLUSI i seguenti: (a) steroidi intranasali, inalatori, topici o iniezione locale di steroidi (per esempio, iniezione intra-articolare); (2) corticosteroidi sistemici a dosi fisiologiche =10 mg/giorno di prednisone o equivalente; (3) steroidi come premedicazione per reazioni di ipersensibilità (per esempio, premedicazione per tomografia computerizzata [TAC])
2.2. I fattori di crescita ECCETTO ove indicato per il trattamento di mielosoppressione correlata all’intervento dello studio e per la profilassi di mielosoppressione ripetuta dopo la manifestazione iniziale
2.3. Trattamenti a base di erbe con proprietà immunostimolanti (ad es. estratto di vischio) o noti per interferire potenzialmente con le funzioni degli organi principali (ad es. ipericina)
2.4. Altri inibitori di riparazione del DNA danneggiato (ad eccezione PARPi) (ad es., gli inibitori di ATR, chinasi dell’atassia teleangectasia [ATM] mutata, protein chinasi DNA-dipendente [DNA-PK], o chinasi Wee).

E.5 End points

E.5.1

Primary end point(s)

Part A: Occurrence of dose-limiting toxicities (DLTs) during the DLT observation period.
Part B: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors
version (RECIST) v1.1

Parte A: Comparsa di tossicità dose-limitanti (DLT) durante il periodo di osservazione delle DLT
Parte B: Sopravvivenza libera da progressione (PFS) in base ai criteri di valutazione della risposta nei tumori solidi (RECIST) v1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

Part A: Up to 3 weeks.
Part B: Up to 3 years.

Parte A: Fino a 3 settimane
Parte B: Fino a 3 anni

E.5.2

Secondary end point(s)

Part A:
-Occurrence of treatment-emergent adverse events (TEAEs) and treatment-related adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).
-Confirmed best overall response (BOR).
-Progression-free survival (PFS) from date of first dose of study intervention until progressive disease (PD) or death.
- Duration of response (DOR) as assessed from complete response (CR) or partial response (PR) until PD, death, or last tumor assessment.
-Time to progression (TTP) from first dose of study intervention until PD.
-All the above by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and/or cancer antigen 125 (CA-125) response (Gynecologic Cancer Intergroup [GCIG] criteria), as assessed by the Investigator.
-Time to first subsequent therapy (TFST)
-PK parameter estimates for M6620 and summary statistics for avelumab.
Part B:
-Occurrence of TEAEs and treatment-related AEs and immune-related adverse events (irAEs) according to NCICTCAE.
-PFS according to GCIG CA-125 as assessed by the Investigator.
-Confirmed BOR according to RECIST v1.1, irRECIST, and GCIG CA-125.
- DOR assessed from CR or PR until PD, death, or last tumor assessment.
- TTP
- TFST
- PK parameter estimates for M6620
- PK summary statistics for avelumab
- Immunogenicity of avelumab in combination therapy as measured by ADA assay from all participants treated with carboplatin + M6620 + avelumab in Part A and Part B.

Comparsa di eventi avversi emergenti dal trattamento (TEAE) ed eventi avversi (EA) correlati al trattamento, secondo i Criteri di terminologia comuni per gli eventi avversi del National Cancer Institute (NCI-CTCAE)
• Migliore risposta complessiva (BOR) confermata
• Sopravvivenza libera da progressione (PFS) dalla data della prima dose dell’intervento dello studio fino alla progressione della malattia (PD) o al decesso
• Durata della risposta (DOR) valutata dalla risposta completa (CR) o dalla risposta parziale (PR) fino a PD, decesso o ultima valutazione del tumore
• Tempo alla progressione (TTP) dalla prima dose dell’intervento dello studio fino alla PD
Tutti gli endpoint precedenti valutati dallo sperimentatore in base alla versione 1.1 dei Criteri di valutazione della risposta nei tumori solidi (RECIST v1.1) e/o risposta dell’antigene tumorale 125 (CA-125) (criteri dell’intergruppo per i tumori ginecologici [GCIG]).
• Tempo alla prima terapia successiva (TFST)
• Stime dei parametri PK di M6620
• Statistiche riassuntive della PK di avelumab
Comparsa di TEAE ed EA correlati al trattamento ed eventi avversi immuno-correlati (EAic) secondo i criteri NCI-CTCAE
• PFS secondo i criteri CA-125 valutato dallo sperimentatore secondo i criteri GCIG
• BOR confermata secondo i criteri RECIST v1.1 e CA-125 secondo i criteri GCIG
• DOR valutata dalla CR o dalla PR fino a PD, decesso o ultima valutazione del tumore
• TTP
• TFST
• Stime dei parametri PK di M6620
• Statistiche riassuntive della PK di avelumab
Immunogenicità di avelumab in terapia combinata, misurata tramite dosaggio degli ADA da tutte le partecipanti trattate con carboplatino + M6620 + avelumab nella Parte A e nella Parte B

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to 3 years

Fino a 3 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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase Ib Safety Run-in

Run-in di sicurezza di fase Ib

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

United States

Belgium

Italy

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 of 1 year after the last participant received the last dose or dies, whichever comes first.

La fine dello studio è definita come la data a 1 anno dopo che l’ultima partecipante abbia ricevuto l’ultima dose o sia deceduta, a seconda di quale evento si verifichi prima

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

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)

Upon withdrawal from the study, participants may receive whatever care they and their physicians agree upon.

In caso di ritiro dallo studio, le partecipanti possono ricevere la cura concordata con i propri medici.

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

2019-05-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-20

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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