Multiple Myeloma
Conditions
Keywords
Multiple myeloma, B-cell maturation antigen, BCMA, anti-BCMA, BCMA-directed, chimeric antigen receptor, CAR-T, PHE885
Brief summary
This was a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of autologous T cells genetically engineered with a novel B-cell Maturation Antigen (BCMA)-specific chimeric antigen receptor (CAR) and manufactured with a new process. CAR-T cells were investigated as a single agent in multiple myeloma
Detailed description
This was a phase I, open label study to characterize the safety and tolerability of a novel B-cell Maturation Antigen (BCMA)-specific chimeric antigen receptor (CAR) manufactured with a new process. In the dose escalation part (Part A) of the study, the anti-BCMA CAR-T cell therapy was studied in adult multiple myeloma (MM) subjects who were relapsed and/or refractory. In the dose evaluation part (Part B) of the study, the anti-BCMA CAR-T cell therapy was studied in newly diagnosed adult subject with MM.
Interventions
BIOLOGICALPHE885
Infusion
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Part A: Subjects with MM who are relapsed and/or refractory to at least 2 prior treatment regimens, including an IMiD (e.g. lenalidomide or pomalidomide), a proteasome inhibitor (e.g. bortezomib, carfilzomib), and an approved anti-CD38 antibody (e.g. daratumumab), if available, and have documented evidence of disease progression (IMWG criteria) * Part A: ECOG performance status that is either 0 or 1 at screening * Part B: Subjects with newly diagnosed multiple myeloma (NDMM) who have received a minimum of 4 and up to 6 cycles of standard induction therapy with VRd, D-VRd, or D-Rd, and have achieved a response of PR or better. One cycle of CyBorDex is allowed prior to induction. * Part B: ECOG performance status that is either 0,1 or 2 at screening * Measurable disease as defined by the protocol * Adequate hematological values * Must have a leukapheresis material of non-mobilized cells accepted for manufacturing
Exclusion criteria
* Prior administration of a genetically modified cellular product including prior BCMA CAR-T therapy. Patients who have received prior BCMA-directed bi-specific antibodies or antibody-drug conjugates (ADC) are not excluded. * Autologous HSCT within 6 weeks prior to enrollment or any prior history of allogeneic hematopoietic stem cell transplant (HSCT) * Chemotherapy or any concomitant anti-cancer therapies (other than protocol prescribed lymphodepletion (LD) chemotherapy) within 2 weeks prior to apheresis * Treatment with small molecule targeted antineoplastics within 2 weeks of apheresis collection or 5 half-lives whichever is shorter * Have received antibodies or immunotherapies (other than daratumumab) within 4 weeks prior to apheresis collection. Daratumumab within 3 weeks prior to apheresis collection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose limiting toxicities (DLT) | 28 days | Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration |
| Nature of Dose limiting toxicities (DLT) | 28 days | Nature of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration |
| Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) | 24 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated) | 24 Months | evaluate the feasibility of the manufacturing process |
| Overall Response Rate (ORR) in Part A | 24 months | Proportion of subjects with the best overall response (BOR) of PR (partial response) or better, as determined by local investigator using the IMWG Criteria |
| ORR in Part B | 24 months | Proportion of subjects with VGPR (very good partial response) or PR to induction therapy who achieve the BOR of PR or better, as determined by local investigator using the IMWG Criteria |
| Response rate at 3 and 6 months in Part A | 3 months, 6 months | Proportion of subjects with the overall response of PR or better at months 3 and 6 after infusion respectively, as determined by local investigator using the IMWG Criteria |
| Overall response rate at 3 and 6 months in Part B | 3 months, 6 months | Proportion of subjects with VGPR or PR to induction therapy who achieve the overall response of PR or better at months 3 and 6 after infusion respectively, as determined by local investigator using the IMWG Criteria |
| Overall Complete Response Rate (CRR) in Part A | 24 months | Proportion of subjects with the BOR of CR or better, as determined by local investigator using the IMWG Criteria |
| Overall CRR in Part B | 24 months | Proportion of subjects with a response of VGPR or PR to induction therapy with the BOR of CR or better, as determined by local investigator using the IMWG Criteria |
| CRR at months 3 and 6 in Part A | 3 months, 6 months | Proportion of subjects with the overall response of CR or better at months 3 and 6 respectively, as determined by local investigator using the IMWG Criteria |
| CRR at months 3 and 6 in Part B | 3 months, 6 months | Proportion of subjects with a response of VGPR or PR to induction therapy with the overall response of CR or better at months 3 and 6 after infusion, respectively, as determined by local investigator using the IMWG Criteria |
| DOR (duration of response) in Part A | from disease response to disease progression, assessed up to approximately 24 months | DOR as assessed by local investigator: the time from achievement of PR or better to relapse or death due to MM (multiple myeloma) |
| DOR in Part B | from disease response to disease progression, assessed up to approximately 24 months | DOR as assessed by local investigator: * The time from the first documented disease response after infusion of CR or better to the date of the first documented progression as assessed by IMGW or death due to MM, for subjects with a response of VGPR or PR to induction therapy, and * The time from the first documented disease response after infusion of PR or better to the date of the first documented progression as assessed by IMGW or death due to MM, for subjects with a response of VGPR or PR to induction therapy |
| Cmax of BCMA CAR-T cells | 24 months | through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow |
| Tmax of BCMA CAR-T cells | 24 months | through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow |
| AUC of BCMA CAR-T cells | 24 months | through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow |
| Clast of BCMA CAR-T cells | 24 months | through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow |
| number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy | 24 Months | — |
Countries
Australia, Israel, Singapore, United States
Outcome results
None listed