PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma

Novartis

Status and phase

Active, not recruiting

Phase 2

Conditions

Multiple Myeloma

Treatments

Biological: PHE885

Study type

Interventional

Funder types

Industry

Identifiers

NCT05172596

CPHE885B12201

2021-003747-22 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment

146 patients

Sex

All

Ages

18 to 99 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

≥18 years of age at the time of informed consent form (ICF) signature
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)
Must be refractory to the last treatment regimen (defined as progressive disease on or within 60 days measured from last dose of last regimen).
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.

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.