BCMA-directed CAR-T Cell Therapy in Adult Patients With Multiple Myeloma

Phase I, Open Label, Study of B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Multiple Myeloma

This is 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 will be investigated as a single agent in multiple myeloma

This is 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 will be studied in adult multiple myeloma (MM) subjects who are relapsed and/or refractory. In the dose evaluation part (Part B) of the study, the anti-BCMA CAR-T cell therapy will be studied in newly diagnosed adult subject with MM.

Multiple myeloma, B-cell maturation antigen, BCMA, anti-BCMA, BCMA-directed, chimeric antigen receptor, CAR-T, PHE885

Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration

Nature of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration

Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated)

Proportion of subjects with the best overall response (BOR) of sCR (stringent complete response) + CR (complete response) + VGPR (very good partial response) + PR (partial response), as determined by local investigator using the IMWG Criteria

Proportion of subjects with the overall response of sCR+CR+VGPR+PR at months 3 and 6 respectively, as determined by local investigator using the IMWG Criteria

Proportion of subjects without progressive disease at month 3 and month 6 after infusion as determined by local investigator using the IMWG Criteria

Proportion of subjects with the BOR of sCR+CR, as determined by local investigator using the IMWG Criteria

Proportion of subjects with the overall response of sCR+CR at months 3 and 6 respectively, as determined by local investigator using the IMWG Criteria

Proportion of subjects with measurable disease at baseline with the overall response of sCR+CR at month 3 and month 6 as determined by local investigator using the IMWG Criteria

DOR as assessed by local investigator: the time from achievement of sCR+CR+VGPR+PR to relapse or death due to MM (multiple myeloma)

number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy

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.