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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Jun 2022 → 21 May 2025

Decision date (initial)

2024-07-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-507140-37-00

EudraCT number

2021-003747-22

ClinicalTrials.gov

NCT05172596

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Pharmacokinetic, Therapy

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

Secondary objectives 10

1. Evaluate the efficacy of durcabtagene autoleucel with respect to MRD negativity in bone marrow measured by next generation sequencing (NGS assay sensitivity of 1 in 105)
2. 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
3. Assess time to next treatment (TTNT) and overall survival (OS)
4. Assess durability of MRD negativity (assay sensitivity of 1 in 105)
5. Assess patient reported outcomes (PRO)
6. Assess the durcabtagene autoleucel manufacturing success rate
7. Assess manufacturing turnaround time
8. Assess safety of durcabtagene autoleucel
9. Assess the cellular kinetics of durcabtagene autoleucel in peripheral blood and bone marrow by qPCR
10. Assess immunogenicity (humoral and cellular) to durcabtagene autoleucel

Conditions and MedDRA coding

Adult patients with relapsed and refractory multiple myeloma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The Trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. ≥18 years of age at the time of informed consent form (ICF) 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.

Exclusion criteria 6

1. Prior administration of a genetically modified cellular product including prior BCMA CAR-T therapy.
2. Participants who have received prior BCMA-directed bi-specific antibodies or anti-BCMA antibody drug conjugate.
3. Known hypersensitivity or contraindication to any product (including its excipients) to be given to the participant as per the study protocol (e.g., durcabtagene autoleucel, tocilizumab and LD agents).
4. Prior autologous SCT within 3 months or allogeneic SCT within 6 months prior to signing informed consent.
5. Active Graft-versus-Host Disease (GVHD), grade 2-4 according to the Mount Sinai GvHD International Consortium criteria or requiring systemic treatment. Note: Systemic therapy for GvHD must have been discontinued at least 2 weeks prior to durcabtagene autoleucel administration.
6. Plasma cell leukemia and other plasmacytoid disorders, non-secretory myeloma without other evidence of measurable disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Best overall response (BOR) per IRC defined as the best disease response recorded from durcabtagene autoleucel administration until PD, death or starting new anticancer therapy whichever comes first, with possible values of either sCR, CR, VGPR, PR, MR, SD, PD or unknown , according to the IMWG criteria. The summary measure for the primary endpoint isORR, defined as the proportion of participants with a BOR of PR or better, assessed in the efficacy analysis set

Secondary endpoints 14

1. Proportion of participants who achieved MRD negative status at any time point within 3 months of achieving at least CR until the time of PD, death or starting new anticancer therapy, whichever comes first.
2. CRR defined as the proportion of participants with BOR of sCR or CR.
3. TTR defined as time from durcabtagene autoleucel administration to the date of first documented response (PR or better).
4. DOR defined as time from first documented response (PR or better) until relapse or death due to any cause.
5. PFS defined as time from durcabtagene autoleucel administration until progression or death due to any cause.
6. TTNT defined as time from durcabtagene autoleucel administration until start of new anti-myeloma therapy or death due to any cause.
7. OS defined as time from durcabtagene autoleucel administration until death due to any cause.
8. Duration from the start of undetectable MRD to the time of reappearance of detectable MRD.
9. Summary scores of PRO measured by EQ-5D-5L, EORTC-QLQ-C30 and EORTC-QLQ-MY20.
10. Proportion of enrolled participants for whom a durcabtagene autoleucel product was manufactured that met all release specifications.
11. Time from pick up of cryopreserved material at the clinic or hospital until return to the clinic or hospital.
12. Type, frequency, and severity of adverse events, serious adverse events, adverse events of special interest (AESIs) and laboratory abnormalities.
13. 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.
14. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 17

Locations

5 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications