Clinical Trials Register

Summary
EudraCT Number:	2019-003583-40
Sponsor's Protocol Code Number:	MS200647_0017
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-05-28
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2019-003583-40

A.3

Full title of the trial

A Phase II, Multicenter, Open Label Study of Bintrafusp alfa (M7824) Monotherapy in
Participants with Advanced, Unresectable Cervical Cancer with Disease Progression During or After Platinum-Containing Chemotherapy

II. fázisú, multicentrikus, nyílt vizsgálat a bintrafusp alfa (M7824) monoterápia értékelésére, olyan előrehaladott, nem reszekálható méhnyakrákban szenvedő betegek esetében, akiknek betegsége a platina tartalmú kemoterápia során vagy az után rosszabbodott

A.3.1

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

Phase II Bintrafusp alfa Monotherapy in Platinum-Experienced Cervical Cancer

A.3.2

Name or abbreviated title of the trial where available

Phase II Bintrafusp alfa Monotherapy in Platinum-Experienced Cervical Cancer

A.4.1

Sponsor's protocol code number

MS200647_0017

A.5.4

Other Identifiers

Name:

IND number

Number:

145485

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 Healthcare 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 Center 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	+496151 72 5200
B.5.5	Fax number	+496151 72 2000
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	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	bintrafusp alfa
D.3.2	Product code	M7824
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	bintrafusp alfa
D.3.9.2	Current sponsor code	M7824
D.3.9.3	Other descriptive name	MSB0011359C
D.3.9.4	EV Substance Code	SUB179957
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cervical Cancer

E.1.1.1

Medical condition in easily understood language

Cervical Cancer

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	10008229
E.1.2	Term	Cervical cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

-To evaluate clinical efficacy of bintrafusp alfa based on ORR

E.2.2

Secondary objectives of the trial

-To evaluate clinical efficacy of bintrafusp alfa based on DOR
-To evaluate clinical efficacy of bintrafusp alfa based on DRR
-To evaluate clinical safety of bintrafusp alfa
-To evaluate clinical efficacy based on PFS
-To evaluate ORR, DOR, DRR, and PFS by Investigator read
- To evaluate clinical efficacy based on OS
- To characterize the PK profile of bintrafusp alfa
- To characterize the immunogenicity of bintrafusp alfa
- To evaluate clinical efficacy of bintrafusp alfa according to PD-L1 expression

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Study participants are ≥ 18 years of age at the time of signing the informed consent. In Japan, if a participant is at least 18 but < 20 years of age, written informed consent from his/her parent or guardian will be required in addition to the participant’s written consent.
2. Participants have a histologically documented advanced unresectable and/or metastatic cervical cancer (squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma) with disease progression during or after the prior platinum-containing chemotherapy:
a. The prior platinum-containing chemotherapy may be:
i. A systemic treatment for advanced unresectable, recurrent, persistent or metastatic disease or
ii. Treatment in the adjuvant or neo-adjuvant setting with disease progression or recurrence within 6 months of completion of platinum containing chemotherapy.
b. Participants who previously only received platinum as a radiosensitizer are not eligible.
c. Participants must be naïve to checkpoint inhibitors as described in Section 5.2 of the Protocol.
3. Measurable disease outside the central nervous system (CNS) according to RECIST 1.1 at Screening. Evidence of measurable disease outside the CNS must be confirmed by IRC prior to start of treatment.
Note: Lesions within the CNS are to be considered as non-target lesions only. Lesions may be considered measurable regardless of prior irradiation. Target lesions should preferably be selected from areas that have not been irradiated, or appear not to have been irradiated,
If necessary, target lesion may be selected from areas that have been, or appear to have been irradiated in the opinion of the assessor.
4. Archival tumor tissue sample or newly obtained (preferred) core or excisional biopsy of a tumor lesion is mandatory and collected during the Screening period prior to enrollment.
Fine needle aspirates are not acceptable.Tumor material must be suitable for biomarker assessment as described in the Laboratory Manual. If participant received local therapy
(e.g., radiation therapy or chemoradiotherapy) after the archival tissue was taken, a new, acceptable biopsy will be required prior to study entry.
5. Have Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 at study entry and Day 1 of treatment with bintrafusp alfa.
6. Life expectancy ≥ 12 weeks as judged by the Investigator.
7. Have adequate organ function: (as defined in Section 5.1)
8. Participants with known HIV infections are in general eligible if the following criteria are met (FDA Guidance on Cancer Clinical Trial Eligibility, March 2019): (as defined in Section 5.1)
9. Participants with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections are in general eligible if the following criteria are met (FDA Guidance on Cancer Clinical Trial Eligibility, March 2019):(as defined in Section 5.1)

E.4

Principal exclusion criteria

1. Participants with active (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 4 weeks, and are not using steroids for at least 7 days prior to the start of study treatment. NB Lesions in the CNS at baseline must be assessed as non-target lesions only.
2. Participants with interstitial lung disease or has had a history of pneumonitis that has required oral or intravenous (IV) steroids.
3. Participants with significant acute or chronic infections.
4. Participants with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
5. Participants with clinically significant cardiovascular/cerebrovascular disease including: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia.
- Other protocol defined exclusion criteria could apply.

E.5 End points

E.5.1

Primary end point(s)

- Confirmed objective response according to RECIST 1.1 assessed by an IRC

E.5.1.1

Timepoint(s) of evaluation of this end point

Time from first treatment to planned final assessment at approximately 2 years.

E.5.2

Secondary end point(s)

1. DOR according to RECIST 1.1 assessed by an IRC
2. Durable response of at least 6 months according to RECIST 1.1 assessed by an IRC
3. Occurrence of TEAEs and treatment-related AEs including AEs of special interest
4. PFS according to RECIST 1.1 assessed by an IRC
5. Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
6. Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
7.Durable Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
8. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
9. OS
10. The concentration observed immediately at the end of infusion (CEOI) of bintrafusp alfa
11. The concentration observed immediately before next dosing (corresponding to pre-dose or trough concentration [Ctrough] for multiple dosing) of bintrafusp alfa
12. Immunogenicity of bintrafusp alfa as measured by ADA assay from Screening through Safety Follow-up Visit (up to 28 days after last treatment)
13. Efficacy endpoints by PD-L1 expression in tumor

E.5.2.1

Timepoint(s) of evaluation of this end point

Time from first treatment to planned final assessment at approximately 2 years

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

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

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

Argentina

Australia

Belgium

Brazil

China

France

Hungary

Japan

Korea, Republic of

Russian Federation

Spain

United States

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

The end of the study is defined as the date when 67% of all study participants and 67% of the participants from China have died (in case of additional China enrollment after global enrollment completion) whichever occurs last. However, the study ends when each participant was followed up for at least 3 years after the first dose if it occurs earlier.

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:

122

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

135

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)

Standard of Care, or, for participants still benefitting from the IMP access is provided via a rollover study, expanded access, marketed product, or another mechanism of access as appropriate.

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

2020-06-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-01-03

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