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. MedDRA version: 21.
Conditions
Interventions
Product Name: Durcabtagene autoleucel
Product Code: PHE885
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Durcabtagene autoleucel
Current Sponsor code: PHE885
Other descriptive na
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. =18 years of age at the time of informed consent form (ICF) XML File Identifier: XCoD+oo9kWY4cmTprypP05dS2nE= Page 11/30 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 81 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of durcabtagene autoleucel with respect to disease response per independent review committee (IRC) in participants infused with durcabtagene autoleucel ;Secondary Objective: • 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 ;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). ;Timepoint(s) of evaluation of this end point: Efficacy interim analysis (6 months after the first 60 pts | — |
Secondary
| Measure | Time frame |
|---|---|
| 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;Timepoint(s) of evaluation of this end point: Efficacy interim anal | — |
Countries
Australia, Brazil, Canada, France, Germany, Greece, Israel, Italy, Japan, Saudi Arabia, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed