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

A Phase 2 Study of PHE885, B-cell Maturation Antigen (BCMA)- Directed CAR-T Cells in Adult Participants With Relapsed and Refractory Multiple Myeloma.

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

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: PHE885

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Novartis Investigative Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Novartis Investigative Site
• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Novartis Investigative Site
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01509-900
      • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Novartis Investigative Site
• France
  • Lille, France, 59037
    • Novartis Investigative Site
  • Nantes, France, 44093
    • Novartis Investigative Site
  • Paris, France, 75475
    • Novartis Investigative Site
  • Poitiers, France, 86021
    • Novartis Investigative Site
• Germany
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Novartis Investigative Site
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 106 76
    • Novartis Investigative Site
  • Thessaloniki, Greece, 570 10
    • Novartis Investigative Site
• Israel
  • Ramat Gan, Israel, 5265601
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • MI
    • Milan, MI, Italy, 20133
      • Novartis Investigative Site
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 4678602
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060 8648
      • Novartis Investigative Site
  • Kyoto
    • Kyoto, Kyoto, Japan, 602-8566
      • Novartis Investigative Site
  • Miyagi
    • Sendai, Miyagi, Japan, 980 8574
      • Novartis Investigative Site
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• Spain
  • Salamanca, Spain, 37007
    • Novartis Investigative Site
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Novartis Investigative Site
• United Kingdom
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • Novartis Investigative Site
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • Novartis Investigative Site
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine-Winship Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PHE885; Patients will receive PHE885	Biological: PHE885; Intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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'	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CRR)	Percentage of patients with BOR of sCR or CR according to the IMWG criteria	24 Months
Time to response	Time form PHE885 infusion to the date of first documented response (PR or better)	24 Months
Duration of Response (DOR)	Time from first documented response (PR or better) until relapse or death due to any cause	24 Months
Progression free survival (PFS)	Time from PHE885 infusion until progression or death due to any cause	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	24 Months
Overall Survival (OS)	Time from PHE885 infusion until death due to any cause	24 Months
Patient Reported Outcomes (PRO): EORTC-QLQ-C30	PROs as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30) Questionnaire will be used as a measure of health-related quality of life.	24 months
Patient Reported Outcomes (PRO): EQ-5D-5L Health Questionnaire	PROs as measured by EuroQoL Group EQ-5D-5L Health Questionnaire is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal.	24 months
Patient Reported Outcomes (PRO): EORTC-QLQ-MY20	PROs as measured by EORTC-QLQ-MY20 is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality.	24 months
PHE885 manufacturing success rate	Percentage of enrolled patients for whom PHE885 product was manufactured that met all release specifications	24 Months
Manufacturing turnaround time	Time from pick of cryopreserved material at the clinic or hospital until return to the clinical or hospital	24 months
Immunogenicity to PHE885	Summary of pre-existing and treatment-induced immunogenicity (cellular and humoral) of PHE885	24 Months
Transgene of PHE885 concentrations over time in peripheral blood and bone marrow	As determined by quantitative polymerase chain reaction (qPCR)	24 Months
Cellular kinetics parameter: Cmax	The maximum transgene level at Tmax	24 Months
Cellular kinetics parameter: Tmax	The time to peak transgene level	24 Months
Cellular kinetics parameter: AUC	The Area under the curve of the transgene level	24 months
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)	24 months
Durability of Minimal Residual Disease (MRD)negativity	Time from the start of undetectable MRD to the time of reappearance of detectable MRD	24 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key Secondary Outcome Measure	Evaluate the efficacy of PHE885 with respect to MRD negativity rate in bone marrow measured by next generation sequencing (NGS)	24 Months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Actual): May 21, 2025
• Study Completion (Actual): May 21, 2025

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: December 22, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 10, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Multiple myeloma; CAR-T; BCMA; chimeric antigen receptor; B-cell maturation antigen; BCMA-directed; PHE885
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: CPHE885B12201; 2021-003747-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The Trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No