Clinical Trial Page

Summary
EudraCT Number:2021-003747-22
Sponsor's Protocol Code Number:CPHE885B12201
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: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
A. Protocol Information
A.1Member State ConcernedGermany - PEI
A.2EudraCT number2021-003747-22
A.3Full 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.3.1Title 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.4.1Sponsor's protocol code numberCPHE885B12201
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorNovartis Pharma AG
B.1.3.4CountrySwitzerland
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportNovartis Pharma AG
B.4.2CountrySwitzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationNovartis Pharma GmbH
B.5.2Functional name of contact pointMedizinischer Infoservice (MCC)
B.5.3 Address:
B.5.3.1Street AddressRoonstrasse 25
B.5.3.2Town/ cityNurnberg
B.5.3.3Post code90429
B.5.3.4CountryGermany
B.5.4Telephone number+4991127312100
B.5.5Fax number+4991127312160
B.5.6E-mailinfoservice.novartis@novartis.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameDurcabtagene autoleucel
D.3.2Product code PHE885
D.3.4Pharmaceutical form Dispersion for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNDurcabtagene autoleucel
D.3.9.2Current sponsor codePHE885
D.3.9.3Other descriptive nameAutologous T cells encoding a chimeric antigen receptor targeting human B cell maturation antigen
D.3.9.4EV Substance CodeSUB224185
D.3.10 Strength
D.3.10.1Concentration unit Other
D.3.10.2Concentration typerange
D.3.10.3Concentration number5 x 10^6 to 10 x 10^6
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Yes
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product Yes
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms Yes
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another 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.1.1Medical 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.1.1.1Medical condition in easily understood language
relapsed and refractory Multiple Myeloma
E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.0
E.1.2Level LLT
E.1.2Classification code 10028228
E.1.2Term Multiple myeloma
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main 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.2.2Secondary 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.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. ≥18 years of age at the time of informed consent form (ICF)
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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.4Principal 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.5.1Primary 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.5.1.1Timepoint(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.5.2Secondary 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.5.2.1Timepoint(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.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Immunogenicity
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other Yes
E.8.1.7.1Other trial design description
Open label
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned4
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA14
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If 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.8.7Trial 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.8.9.1In the Member State concerned years3
E.8.9.1In the Member State concerned months8
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years3
E.8.9.2In all countries concerned by the trial months8
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 81
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 55
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state10
F.4.2 For a multinational trial
F.4.2.1In the EEA 46
F.4.2.2In 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
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-07-05
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-08-02
P. End of Trial
P.End of Trial StatusOngoing

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Medical Conditions

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