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

Phase 1

Active, not recruiting

• Conditions: Multiple Myeloma
• Interventions: Biological: PHE885

• Registration Number: NCT04318327
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This is 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 will be investigated as a single agent in multiple myeloma

Detailed Description

This is 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 will be studied in adult multiple myeloma (MM) subjects who are relapsed and/or refractory. In the dose evaluation part (Part B) of the study, the anti-BCMA CAR-T cell therapy will be studied in newly diagnosed adult subject with MM.

Study Timeline

• Study First Submitted: 2020-03-20
• Study First Submitted QC: 2020-03-20
• Study First Posted: 2020-03-23
• Study Start: 2020-07-23
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-25
• Last Update Posted: 2024-11-27
• Primary Completion: 2026-02-19
• Study Completion: 2026-02-19

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 96

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PHE885 (Part A)	PHE885	Relapsed and/or refractory multiple myeloma (r/r MM) patients will receive PHE885.
PHE885 (Part B)	PHE885	Newly diagnosed multiple myeloma (NDMM) patients will receive PHE885.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Overall Complete Response Rate (CRR) in Part A	24 months	Proportion of subjects with the BOR of CR or better, as determined by local investigator using the IMWG Criteria
Overall CRR in Part B	24 months	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
DOR (duration of response) in Part A	from disease response to disease progression, assessed up to approximately 24 months	DOR as assessed by local investigator: the time from achievement of PR or better to relapse or death due to MM (multiple myeloma)
Overall Response Rate (ORR) in Part A	24 months	Proportion of subjects with the best overall response (BOR) of PR (partial response) or better, as determined by local investigator using the IMWG Criteria
ORR in Part B	24 months	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
Response rate at 3 and 6 months in Part A	3 months, 6 months	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
Tmax of BCMA CAR-T cells	24 months	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy	24 Months
Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated)	24 Months	evaluate the feasibility of the manufacturing process
Overall response rate at 3 and 6 months in Part B	3 months, 6 months	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
Cmax of BCMA CAR-T cells	24 months	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
AUC of BCMA CAR-T cells	24 months	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
CRR at months 3 and 6 in Part A	3 months, 6 months	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
CRR at months 3 and 6 in Part B	3 months, 6 months	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
DOR in Part B	from disease response to disease progression, assessed up to approximately 24 months	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
Clast of BCMA CAR-T cells	24 months	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow

Trial Locations

Locations (5)

University of Chicago Medical Center Hematology and Oncology; 🇺🇸 Chicago, Illinois, United States

Beth Israel Deaconess Medical Cente KS121; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute Main Centre; 🇺🇸 Boston, Massachusetts, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Novartis Investigative Site; 🇸🇬 Singapore, Singapore