Clinical Trials Register

Summary
EudraCT Number:	2016-002122-36
Sponsor's Protocol Code Number:	64007957MMY1001
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-07-30
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

Germany - PEI

A.2

EudraCT number

2016-002122-36

A.3

Full title of the trial

A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Teclistamab, a Humanized BCMA x CD3 Bispecific Antibody, in Subjects with Relapsed or Refractory Multiple Myeloma

A.3.1

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

An Open label Study of Teclistamab in Subjects with Relapsed and Refractory Multiple Myeloma

A.4.1

Sponsor's protocol code number

64007957MMY1001

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	Janssen-Cilag International NV
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	Janssen Research & Development, LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31 71 524 21 66
B.5.5	Fax number	+31 71 524 21 10
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	TECVAYLI
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International N.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	JNJ-64007957
D.3.2	Product code	JNJ-64007957
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Teclistamab
D.3.9.2	Current sponsor code	JNJ-64007957
D.3.9.3	Other descriptive name	JNJ-64007957-AAA
D.3.9.4	EV Substance Code	SUB185866
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	Yes
D.3.11.13.1	Other medicinal product type	Human IgG4 bispecific antibody against BCMA and CD3
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	Yes
D.2.1.1.1	Trade name	TECVAYLI
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International N.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	JNJ-64007957
D.3.2	Product code	JNJ-64007957
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Teclistamab
D.3.9.2	Current sponsor code	JNJ-64007957
D.3.9.3	Other descriptive name	JNJ-64007957-AAA
D.3.9.4	EV Substance Code	SUB185866
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	90
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	Yes
D.3.11.13.1	Other medicinal product type	Human IgG4 bispecific antibody against BCMA and CD3

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

Relapsed or Refractory Multiple Myeloma

E.1.1.1

Medical condition in easily understood language

Multiple Myeloma

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	HLGT
E.1.2	Classification code	10005330
E.1.2	Term	Blood and lymphatic system disorders congenital
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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 1 (Dose Escalation): To identify the recommended Phase 2 dose(s) and schedule assessed to be safe for JNJ-64007957
•Part 2 (Dose Expansion): To characterize the safety and tolerability of JNJ-64007957 at the recommended Phase 2 dose(s) (RP2Ds)
•Part 3 (Phase 2) for Cohorts A and C: To evaluate the efficacy of teclistamab at the RP2D

E.2.2

Secondary objectives of the trial

•To characterize the pharmacokinetics and pharmacodynamics of teclistamab
•To evaluate the preliminary antitumor activity of JNJ 64007957 at the RP2D(s) in Part 2
Part 3 for Cohorts A and C:
•To further assess the efficacy of teclistamab at the RP2D
•To evaluate MRD at the RP2D
•To further assess the safety and tolerability of teclistamab at the RP2D

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. ≥18 years of age.
2. Documented diagnosis of MM according to IMWG diagnostic criteria.
3. Part 1 and Part 2
Measurable MM that is relapsed or refractory to established therapies with known clinical benefit in relapsed/refractory MM or be intolerant of those established MM therapies, and a candidate for teclistamab treatment in the opinion of the treating physician. Prior lines of therapy must include a PI, an IMiD and an anti-CD38 monoclonal antibody in any order during the course of treatment. Subjects who could not tolerate a PI, IMiD, or an anti-CD38 monoclonal antibody are allowed. In Part 2 (dose expansion), in addition to above criteria, MM must be measurable per current IMWG published guidelines by central lab assessment. If central lab assessment is not available, relevant local lab measurement must exceed the minimum required level by at least 25%.
Part 3
Measurable disease
Cohort A and Cohort C: MM must be measurable by central lab assessment:
- Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
- Light chain MM without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio. If central lab assessments are not available, relevant local lab measurements must exceed the min required level by at least 25%.
Prior treatment:
- Cohort A: Subjects must have 1) received ≥3 prior lines of therapy and 2) previously received a PI, an IMiD, and an anti-CD38 monoclonal
antibody.
- Cohort C: received ≥3 prior lines of therapy that included a PI, an IMiD, an anti-CD38 monoclonal antibody, and an anti-BCMA treatment (with
CAR-T cells or an ADC).
4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
5. Pretreatment clinical laboratory values meeting the following criteria during the Screening Phase (refer to clinical protocol)
6. A female subject of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (β human chorionic gonadotropin [β-hCG]) or urine.
7. Female subjects of childbearing potential and fertile male subjects who are sexually active must agree to use a highly effective method of contraception (<1% / year failure rate). Contraception must begin from the time of signing the ICF, continue during study treatment, including dose interruptions, and through 6 months and 3 months after the last dose of study drug, for female and male subjects, respectively. Contraception must be consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials.
When a female subject is of childbearing potential the following are required:
• Subject must agree to practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly). Examples of highly effective contraceptives include:
– user-independent methods: 1) implantable progestogen-only hormone contraception associated with inhibition of ovulation; 2) intrauterine device; intrauterine hormone-releasing system; 3) vasectomized partner;
– user-dependent methods: 1) combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral orintravaginal or transdermal; 2) progestogen-only hormone contraception associated with inhibition of ovulation (oral or injectable)

In addition to the highly effective method of contraception, a fertile male subject:
- Who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception
-Who is sexually active with a woman who is pregnant must use a condom
-Female and male subjects must agree not to donate eggs (ova, oocytes) or sperm, during the study and for 6 months and 3 months, respectively, after the last dose of study drug.

For full inclusion criteria, refer to section 4.1 inclusion criteria of the protocol.

E.4

Principal exclusion criteria

1. Prior treatment with any BCMA-targeted therapy, with the exception of Cohort C in Part 3.
2. Prior antitumor therapy as follows, before the first dose of study drug:
-Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less.
-Monoclonal antibody treatment for multiple myeloma within 21 days
-Cytotoxic therapy within 21 days
-Proteasome inhibitor therapy within 14 days
-Immunomodulatory agent therapy within 7 days
-Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, natural killer [NK] cells) within 3 months
-Radiotherapy within 14 days or focal radiation within 7 days.
3. Toxicities from previous anticancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
4. Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study drug. (does not include pretreatment medication)
5. Stem cell transplantation:
-An allogeneic stem cell transplant within 6 months. Subjects who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease.
-Received an autologous stem cell transplant ≤12 weeks before the first dose of study drug.
6. Known active CNS involvement or exhibits clinical signs of meningeal involvement of multiple myeloma.
7. Plasma cell leukemia (>2.0 x 10^9/L plasma cells by standard differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloid light-chain amyloidosis.
8. Known to be seropositive for human immunodeficiency virus or acquired immune deficiency syndrome.
9.Hepatitis B infection or at risk for hepatitis B virus (HBV) reactivation as defined according to the American Society of Clinical Oncology guidelines. Active Hepatitis C infection as measured by positive hepatitis C virus (HCV)-RNA testing in subjects with positive anti-HCV antibody or subjects with history of HCV antibody positivity.
10. Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation.
11. Known allergies, hypersensitivity, or intolerance to the study drug (teclistamab) or its excipients.
12. Any serious underlying medical condition.
13. Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after receiving the last dose of study drug.
14. Plans to father a child while enrolled in this study
or within 3 months after receiving the last dose of study drug.
15. Major surgery within 2 weeks of the first dose, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration.
16. The following cardiac conditions:
- New York Heart Association stage III or IV congestive heart failure
-Myocardial infarction or coronary artery bypass graft (CABG) ≤6 months prior to enrollment
-History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
-History of severe non-ischemic cardiomyopathy
17. Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma.
18. Live, attenuated vaccine within 4 weeks prior to the first dose of teclistamab. Non-live or non-replicating vaccines authorized for emergency use (eg., COVID-19) are allowed.

For full exclusion criteria, refer to Section 4.2 exclusion criteria of the clinical protocol.

E.5 End points

E.5.1

Primary end point(s)

•Part 1 (Dose Escalation): Frequency and type of dose-limiting toxicity (DLT)
•Part 2 (Dose Expansion): Occurrence and severity of adverse events, serious adverse events, and laboratory values
•Part 3 (Phase 2) for Cohorts A and C: ORR (PR or better) as defined by the IMWG criteria

E.5.1.1

Timepoint(s) of evaluation of this end point

Please refer to the clinical protocol for the Schedule of Activities and associated Tables

E.5.2

Secondary end point(s)

•Parts 1 & 2
1. Pharmacokinetic parameters and pharmacodynamic markers including but not limited to depletion of BCMA expressing cells, systemic cytokine concentrations, and markers of T cell activation
2. Assess response rate including ORR as defined by IMWG response criteria
3. progression-free survival (PFS)
4. overall survival (OS)
•Part 3 (phase 2) for Cohorts A and C:
1. DOR
2. Assess additional response parameters as defined by IMWG response criteria
3. PFS
4. OS
5. MRD-negative status
6. Occurence and severity of adverse events, serious adverse events, and laboratory values

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to the clinical protocol for the Schedule of Activities and associated Tables

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

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

-Immunogenicity
-Biomarker
-Immunoregulatory activity

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Dose escalation (Part 1) and expansion (Part 2) and (Part 3) Phase 2 dose expansion

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

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

Canada

China

United Kingdom

United States

Belgium

France

Germany

Italy

Netherlands

Spain

Sweden

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

LSLV

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

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:

234

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

239

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

230

F.4.2.2

In the whole clinical trial

473

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)

Normal treatment

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

2020-11-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-11-05

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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