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

Phase 1TerminatedNCT04318327

Novartis Pharmaceuticals96 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

PHE885BIOLOGICAL

Infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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.

Locations (9)

Uni of Chi Medi Ctr Hema and Onco

Chicago, Illinois, United States

Beth Israel Deaconess Medical Cente

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Medical College of Wisconsin

Outcomes

Primary Outcomes

Incidence of Dose limiting toxicities (DLT)

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

Time frame: 28 days

Nature of Dose limiting toxicities (DLT)

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

Time frame: 28 days

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

Time frame: 24 months

Secondary Outcomes

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

evaluate the feasibility of the manufacturing process

Time frame: 24 Months

Overall Response Rate (ORR) in Part A

Proportion of subjects with the best overall response (BOR) of PR (partial response) or better, as determined by local investigator using the IMWG Criteria

Time frame: 24 months

ORR in Part B

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

Time frame: 24 months

Response rate at 3 and 6 months in Part A

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

Time frame: 3 months, 6 months

Data from ClinicalTrials.gov

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