Multiple Myeloma
Conditions
Keywords
Multiple myeloma, B-cell maturation antigen, BCMA, BCMA-directed, chimeric antigen receptor, CAR-T, PHE885
Brief summary
This is a Phase II study to determine the efficacy and safety of PHE885, a BCMA-directed CAR-T cell therapy, manufactured with a new process. The CAR-T cell therapy will be investigated as a single agent in relapsed and refractory multiple myeloma
Detailed description
This clinical trial employs an open label, single arm, multi-center design with primary analysis testing overall response rate ( ORR), including one interim analysis for futility and one interim analysis for efficacy. The trial population includes adult patients with relapsed and refractory multiple myeloma (MM) after failure of 3 or more 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 per IMWG criteria . In addition, patients must be refractory to the last line of therapy The trial will enroll 90 efficacy evaluable adult patients with relapsed and refractory MM (efficacy evaluable means participants infused with a PHE885 product at target dose 10e6 that met all release specifications). Patients will be followed for acute and intermediate safety and efficacy within this trial for a minimum of 2 years before being transferred to the long-term follow-up trial. A long-term post-study follow-up for lentiviral vector safety will be offered under a separate destination protocol for 15 years post injection per health authority guidelines.
Interventions
BIOLOGICALPHE885
Intravenous (IV) infusion
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. ≥18 years of age at the time of informed consent form (ICF) signature 2. Adult patients after failure of three or more 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 who have documented evidence of disease progression (IMWG criteria) 3, Must have received ≥2 consecutive cycles of treatment for at least three prior regimens unless deemed refractory to that regimen (i.e., progressive disease as the best response) 4\. Must be refractory to the last treatment regimen (defined as progressive disease on or within 60 days measured from last dose of last regimen). 5\. Measurable disease at enrollment as defined by the protocol 6. Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening 7. Must have a leukapheresis material of non-mobilized cells accepted for manufacturing
Exclusion criteria
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\. Prior autologous SCT within 3 month or allogenic SCT within 6 months prior to signing informed consent. 4.Plasma cell (PC) leukemia and other plasmacytoid disorders, other than MM 5.POEMS syndrome 6.Active central nervous system (CNS) involvement by malignancy 7.Patients with active neurological autoimmune or inflammatory disorders 8.Inadequate cardiac, renal, hepatic or hematologic function as defined in the protocol. Other protocol-defined Inclusion/Exclusion may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) per Independent Review Committee (IRC) in Efficacy Analysis Set | 24 Months | Percentage of patients with best overall response (BOR) of either stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) according to the International Myeloma Working Group (IMWG) criteria' |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) | 24 Months | Percentage of patients with BOR of sCR or CR according to the IMWG criteria |
| Time to response | 24 Months | Time form PHE885 infusion to the date of first documented response (PR or better) |
| Duration of Response (DOR) | 24 Months | Time from first documented response (PR or better) until relapse or death due to any cause |
| Progression free survival (PFS) | 24 Months | Time from PHE885 infusion until progression or death due to any cause |
| Time to next anti-myeloma treatment (TTNT) | 24 Months | Time from PHE885 infusion until start of new anti-myeloma therapy or death due to any cause |
| Overall Survival (OS) | 24 Months | Time from PHE885 infusion until death due to any cause |
| Durability of Minimal Residual Disease (MRD)negativity | 24 Months | Time from the start of undetectable MRD to the time of reappearance of detectable MRD |
| Patient Reported Outcomes (PRO): EQ-5D-5L Health Questionnaire | 24 months | PROs as measured by EuroQoL Group EQ-5D-5L Health Questionnaire is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. |
| Key Secondary End point: MRD Negativity rate in Bone Marrow | 24 months | Evaluate the efficacy of PHE885 with respect to MRD negativity rate in bone marrow measured by next generation sequencing (NGS) |
| Patient Reported Outcomes (PRO): EORTC-QLQ-MY20 | 24 months | PROs as measured by EORTC-QLQ-MY20 is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality. |
| PHE885 manufacturing success rate | 24 Months | Percentage of enrolled patients for whom PHE885 product was manufactured that met all release specifications |
| Manufacturing turnaround time | 24 months | Time from pick of cryopreserved material at the clinic or hospital until return to the clinical or hospital |
| Transgene of PHE885 concentrations over time in peripheral blood and bone marrow | 24 Months | As determined by quantitative polymerase chain reaction (qPCR) |
| Cellular kinetics parameter: Cmax | 24 Months | The maximum transgene level at Tmax |
| Cellular kinetics parameter: Tmax | 24 Months | The time to peak transgene level |
| Cellular kinetics parameter: AUC | 24 months | The Area under the curve of the transgene level |
| Immunogenicity to PHE885 | 24 Months | Summary of pre-existing and treatment-induced immunogenicity (cellular and humoral) of PHE885 |
| Patient Reported Outcomes (PRO): EORTC-QLQ-C30 | 24 months | PROs as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30) Questionnaire will be used as a measure of health-related quality of life. |
Countries
Australia, Brazil, Canada, France, Germany, Greece, Israel, Italy, Japan, Saudi Arabia, Singapore, Spain, United Kingdom, United States
Outcome results
None listed