Clinical Trials Register

Summary
EudraCT Number:	2021-003747-22
Sponsor's Protocol Code Number:	CPHE885B12201
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Temporarily Halted
Date on which this record was first entered in the EudraCT database:	2021-12-15
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

2021-003747-22

A.3

Full title of the trial

A Phase 2 study of durcabtagene autoleucel, B-cell maturation Antigen (BCMA)-directed CAR-T Cells in adult participants with relapsed and refractory multiple myeloma

A.3.1

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

Study of durcabtagene autoleucel, in adult patients with relapsed and refractory Multiple Myeloma

A.4.1

Sponsor's protocol code number

CPHE885B12201

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	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma GmbH
B.5.2	Functional name of contact point	Medizinischer Infoservice (MCC)
B.5.3	Address:
B.5.3.1	Street Address	Roonstrasse 25
B.5.3.2	Town/ city	Nurnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4991127312100
B.5.5	Fax number	+4991127312160
B.5.6	E-mail	infoservice.novartis@novartis.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	Durcabtagene autoleucel
D.3.2	Product code	PHE885
D.3.4	Pharmaceutical form	Dispersion 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	Durcabtagene autoleucel
D.3.9.2	Current sponsor code	PHE885
D.3.9.3	Other descriptive name	Autologous T cells encoding a chimeric antigen receptor targeting human B cell maturation antigen
D.3.9.4	EV Substance Code	SUB224185
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 x 10^6 to 10 x 10^6
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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

Adult participants with relapsed and refractory multiple myeloma after failure of 3 or more different prior lines of therapy, including failing an immunomodulatory drug (IMiD), a proteasome inhibitor (PI) and an anti-CD38 (cluster of differentiation 38) monoclonal antibody (mAb), and who have measurable disease at enrollment and documented evidence of progressive disease per IMWG criteria on the last prior therapy. Participants must be refractory to the last line of therapy.

E.1.1.1

Medical condition in easily understood language

relapsed and refractory 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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10028228
E.1.2	Term	Multiple myeloma
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

Evaluate the efficacy of durcabtagene autoleucel with respect to disease response per independent review committee (IRC) in participants infused with durcabtagene autoleucel

E.2.2

Secondary objectives of the trial

• Evaluate the efficacy of durcabtagene autoleucel with respect to MRD negativity in bone
marrow measured by next generation sequencing (NGS)
• Assess additional efficacy outcomes including complete response rate (CRR), time to response (TTR), duration of response (DOR), progression-free survival (PFS) per IRC and local investigator assessment
• Assess time to next treatment (TTNT) and overall survival (OS)
• Evaluate rate of minimal residual disease (MRD) negativity in bone marrow measured by next-generation sequencing (NGS)
• Assess durability of MRD negativity
• Assess patient reported outcomes (PRO)
• Assess the durcabtagene autoleucel manufacturing success rate
• Assess manufacturing turnaround time
• Assess safety of durcabtagene autoleucel
• Assess the cellular kinetics of durcabtagene autoleucel in peripheral blood and bone marrow by qPCR
• Assess immunogenicity (humoral and cellular) to durcabtagene autoleucel

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. ≥18 years of age at the time of informed consent form (ICF)
XML File Identifier: XCoD+oo9kWY4cmTprypP05dS2nE=
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signature.
2. Adult participants with relapsed and refractory multiple myeloma who
have received at least 3 prior lines of therapy including an IMiD (e.g.,
lenalidomide or pomalidomide), a proteasome inhibitor (e.g.,
bortezomib, carfilzomib), and an approved anti-CD38 antibody (e.g.,
daratumumab, isatuximab), and have documented evidence of disease
progression (IMWG criteria).
3. Must be refractory to the last treatment regimen (defined as
progressive disease on or within 60 days measured from last dose of last
regimen).
4. Measurable disease at enrollment as defined by the protocol.
5. Eastern Cooperative Oncology Group (ECOG) performance status that
is either 0 or 1 at screening.
6. Must have a leukapheresis material of non-mobilized cells accepted
for manufacturing.

E.4

Principal exclusion criteria

1. Prior administration of a genetically modified cellular product
including prior BCMA CAR-T therapy. Participants who have received
prior BCMA-directed bi-specific antibodies or anti-BCMA antibody drug
conjugate.
2. Prior autologous stem cell transplantation (SCT) within 3 months or
allogeneic stem cell transplantation within 6 months prior to signing
informed consent.
3. Plasma cell (PC) leukemia and other plasmacytoid disorders, other
than MM.
4. POEMS syndrome (plasma cell dyscrasia with polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein, and skin changes).
5. Active central nervous system (CNS) involvement by malignancy.
6. Participants with active neurological autoimmune or inflammatory
disorders.

E.5 End points

E.5.1

Primary end point(s)

Best overall response (BOR) per IRC defined as the best disease response recorded from Durcabtagene autoleucel administration until progressive disease (PD), death or starting new anticancer therapy whichever comes first, with possible values of either stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), progressive disease (PD) or unknown (UNK), according to the International Myeloma Working Group (IMWG) criteria.
The summary measure for the primary endpoint is overall response rate (ORR), defined as the proportion of participants with a BOR of PR or better, assessed in the efficacy analysis set (EAS).

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy interim analysis (6 months after the first 60 pts),
Primary analysis (6 months after 90 pts) Final analysis (all patients).

E.5.2

Secondary end point(s)

• Proportion of participants who achieved MRD negative status at any
time point within 3 months of achieving at least CR until time of PD,
death or starting new anticancer therapy, whichever comes first
• CRR defined as the proportion of participants with BOR of sCR or CR
• TTR defined as time from durcabtagene autoleucel administration to the date of first
documented response (PR or better)
• DOR defined as time from first documented response (PR or better)
until relapse or death due to any cause
• PFS defined as time from durcabtagene autoleucel administration until progression or
death due to any cause
• TTNT defined as time from durcabtagene autoleucel administration until start of new
anti-myeloma therapy or death due to any cause
• OS defined as time from durcabtagene autoleucel administration until death due to any
cause
• Duration from the start of undetectable MRD to the time of
reappearance of detectable MRD
• Summary scores of PRO measured by EQ-5D-5L, EORTC-QLQ-C30 and
EORTC-QLQ-MY20
• Proportion of enrolled participants for whom a durcabtagene autoleucel product was
manufactured that met all release specifications
• Time from pick up of cryopreserved material at the clinic or hospital
until return to the clinic or hospital.
• Type, frequency, and severity of adverse events, serious adverse
events, adverse events of special interest (AESIs) and laboratory
abnormalities
• Transgene of durcabtagene autoleucel concentrations over time in peripheral blood and
bone marrow determined by quantitative PCR
Cellular kinetics parameters: Cmax (maximum serum concentration),
Tmax (time to reach Cmax), AUCs and other cellular kinetic parameters
• Summary of pre-existing and treatment-induced immunogenicity
(cellular and humoral) of durcabtagene autoleucel
Correlate levels of pre-existing and treatment-induced immunogenicity
with cellular kinetic parameters, safety and efficacy

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy interim analysis (6 months after the first 75 pts),
Primary analysis (6 months after 100 pts) and
Final CSR (24 months after all 100 pts)

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

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

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

Open label

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.8.3

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

Singapore

Australia

Brazil

Canada

Israel

Japan

Saudi Arabia

United Kingdom

United States

France

Germany

Greece

Italy

Spain

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 study is when all participants have completed Month 24 evaluation or progressed or died earlier or were withdrawn prematurely and analysis of primary and secondary end points of the study are performed. Participants who have completed their Month 24 visit before the end of the study will be followed every 1 year until the end of the study.

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

136

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)

Following the end of the study as defined in the protocol, per health authority requirements, all patients who either complete or prematurely discontinue from the study are to be followed up to 15 years post-durcabtagene autoleucel administration. Therefore, a post-study long-term follow-up for lentiviral vector safety monitoring will continue under a separate protocol (CCTL019A2205B).

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

2022-07-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-08-02

P. End of Trial
P.	End of Trial Status	Temporarily Halted

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