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

• ClinicalTrials.gov Identifier: NCT04318327
• Recruitment Status: Active, not recruiting
• First Posted: March 23, 2020
• Last Update Posted: January 25, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: March 20, 2020
• First Posted Date: March 23, 2020
• Last Update Posted Date: January 25, 2024
• Actual Study Start Date: July 23, 2020
• Estimated Primary Completion Date: February 19, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2023)

• Incidence of Dose limiting toxicities (DLT) [ Time Frame: 28 days ]
  Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration
• Nature of Dose limiting toxicities (DLT) [ Time Frame: 28 days ]
  Nature 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) [ Time Frame: 24 months ]

Original Primary Outcome Measures (submitted: March 20, 2020)

• Incidence of Dose limiting toxicities (DLT) [ Time Frame: 24 months ]
  Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration
• Nature of Dose limiting toxicities (DLT) [ Time Frame: 24 months ]
  Nature 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) [ Time Frame: 24 months ]

Current Secondary Outcome Measures (submitted: January 24, 2024)

• Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated) [ Time Frame: 24 Months ]
  evaluate the feasibility of the manufacturing process
• Overall Response Rate (ORR) in Part A [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
• Overall response rate at 3 and 6 months in Part B [ Time Frame: 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
• Overall Complete Response Rate (CRR) in Part A [ Time Frame: 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 [ Time Frame: 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
• CRR at months 3 and 6 in Part A [ Time Frame: 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 [ Time Frame: 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 (duration of response) in Part A [ Time Frame: 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)
• DOR in Part B [ Time Frame: 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
• Cmax of BCMA CAR-T cells [ Time Frame: 24 months ]
  through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
• Tmax of BCMA CAR-T cells [ Time Frame: 24 months ]
  through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
• AUC of BCMA CAR-T cells [ Time Frame: 24 months ]
  through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
• Clast of BCMA CAR-T cells [ Time Frame: 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 [ Time Frame: 24 Months ]

Original Secondary Outcome Measures (submitted: March 20, 2020)

• Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated) [ Time Frame: 24 Months ]
  evaluate the feasibility of the manufacturing process
• ORR (overall response rate): Proportion of subjects with the best overall response (BOR) [ Time Frame: month 3, month 6 ]
  BOR (best overall response) of sCR (stringent complete response) +CR (complete response) +VGPR (very good partial response)+PR (partial response) at Months 3 and 6, as determined by local investigator using the IMWG (International Myeloma Working Group) Criteria (Kumar et al, 2016)
• CRR (complete response rate) [ Time Frame: 3 months ]
  Proportion of subjects with the BOR of sCR+CR at Month 3, as determined by local investigator using the IMWG Criteria.
• DOR (duration of response) [ Time Frame: 12 months ]
  as assessed by local investigator: the time from achievement of sCR+CR+VGPR+PR to relapse or death due to MM (multiple myeloma)
• Cmax of BCMA CAR-T cells [ Time Frame: 24 months ]
  through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
• Tmax of BCMA CAR-T cells [ Time Frame: 24 months ]
  through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
• AUC of BCMA CAR-T cells [ Time Frame: 24 months ]
  through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
• Clast of BCMA CAR-T cells [ Time Frame: 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 [ Time Frame: 24 Months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: BCMA-directed CAR-T Cell Therapy in Adult Patients With Multiple Myeloma
• Official Title: Phase I, Open Label, Study of B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Multiple Myeloma
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

Biological: PHE885

Infusion

Study Arms

• Experimental: PHE885 (Part A)
  Relapsed and/or refractory multiple myeloma (r/r MM) patients will receive PHE885.
  Intervention: Biological: PHE885
• Experimental: PHE885 (Part B)
  Newly diagnosed multiple myeloma (NDMM) patients will receive PHE885.
  Intervention: Biological: PHE885

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 5, 2023): 96
• Original Estimated Enrollment (submitted: March 20, 2020): 16
• Estimated Study Completion Date: February 19, 2026
• Estimated Primary Completion Date: February 19, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Israel, Singapore, United States

Administrative Information

• NCT Number: NCT04318327
• Other Study ID Numbers: CADPT07A12101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: January 2024