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 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

Study Overview

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

Detailed Description

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
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Novartis Investigative Site
• Israel
  • Ramat Gan, Israel, 5265601
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Uni of Chi Medi Ctr Hema and Onco
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Cente
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PHE885 (Part A); Relapsed and/or refractory multiple myeloma (r/r MM) patients will receive PHE885.	Biological: PHE885; Infusion
Experimental: PHE885 (Part B); Newly diagnosed multiple myeloma (NDMM) patients will receive PHE885.	Biological: PHE885; Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)		24 months
Incidence of Dose limiting toxicities (DLT)	Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration	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	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 Months
Cmax of BCMA CAR-T cells	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow	24 months
Tmax of BCMA CAR-T cells	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow	24 months
AUC of BCMA CAR-T cells	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow	24 months
Clast of BCMA CAR-T cells	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow	24 months
number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy		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	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	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	3 months, 6 months
Overall response rate at 3 and 6 months in Part B	Proportion of subjects with VGPR or PR to induction therapy who achieve the overall response of PR or better at months 3 and 6 after infusion respectively, as determined by local investigator using the IMWG Criteria	3 months, 6 months
Overall Complete Response Rate (CRR) in Part A	Proportion of subjects with the BOR of CR or better, as determined by local investigator using the IMWG Criteria	24 months
Overall CRR in Part B	Proportion of subjects with a response of VGPR or PR to induction therapy with the BOR of CR or better, as determined by local investigator using the IMWG Criteria	24 months
CRR at months 3 and 6 in Part A	Proportion of subjects with the overall response of CR or better at months 3 and 6 respectively, as determined by local investigator using the IMWG Criteria	3 months, 6 months
CRR at months 3 and 6 in Part B	Proportion of subjects with a response of VGPR or PR to induction therapy with the overall response of CR or better at months 3 and 6 after infusion, respectively, as determined by local investigator using the IMWG Criteria	3 months, 6 months
DOR (duration of response) in Part A	DOR as assessed by local investigator: the time from achievement of PR or better to relapse or death due to MM (multiple myeloma)	from disease response to disease progression, assessed up to approximately 24 months
DOR in Part B	DOR as assessed by local investigator: The time from the first documented disease response after infusion of CR or better to the date of the first documented progression as assessed by IMGW or death due to MM, for subjects with a response of VGPR or PR to induction therapy, and; The time from the first documented disease response after infusion of PR or better to the date of the first documented progression as assessed by IMGW or death due to MM, for subjects with a response of VGPR or PR to induction therapy	from disease response to disease progression, assessed up to approximately 24 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• CADPT07A12101 Clinical Trial Results

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Actual): April 29, 2025
• Study Completion (Actual): April 29, 2025

Study Registration Dates

• First Submitted: March 20, 2020
• First Submitted That Met QC Criteria: March 20, 2020
• First Posted (Actual): March 23, 2020

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 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; anti-BCMA
• 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: CADPT07A12101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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