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

Phase 2TerminatedNCT05172596

Novartis Pharmaceuticals146 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

146

Conditions

Multiple Myeloma

Interventions

PHE885BIOLOGICAL

Intravenous (IV) infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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.

Locations (36)

Outcomes

Primary Outcomes

Overall response rate (ORR) per Independent Review Committee (IRC) in Efficacy Analysis Set

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'

Time frame: 24 Months

Secondary Outcomes

Key Secondary End point: MRD Negativity rate in Bone Marrow

Evaluate the efficacy of PHE885 with respect to MRD negativity rate in bone marrow measured by next generation sequencing (NGS)

Time frame: 24 months

Complete response rate (CRR)

Percentage of patients with BOR of sCR or CR according to the IMWG criteria

Time frame: 24 Months

Time to response

Time form PHE885 infusion to the date of first documented response (PR or better)

Time frame: 24 Months

Duration of Response (DOR)

Time from first documented response (PR or better) until relapse or death due to any cause

Time frame: 24 Months

Progression free survival (PFS)

Time from PHE885 infusion until progression or death due to any cause

Time frame: 24 Months

Time to next anti-myeloma treatment (TTNT)

Time from PHE885 infusion until start of new anti-myeloma therapy or death due to any cause

Time frame: 24 Months

Data from ClinicalTrials.gov

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Palo Alto, California, United States

Emory University School of Medicine-Winship Cancer Institute

Atlanta, Georgia, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Oregon Health Sciences University

Portland, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Fred Hutch Cancer Research

Seattle, Washington, United States

Novartis Investigative Site

Camperdown, New South Wales, Australia

Novartis Investigative Site

Melbourne, Victoria, Australia

Novartis Investigative Site

Salvador, Estado de Bahia, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

...and 26 more locations