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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05172596

Collaborator

(none)

100

Enrollment

Locations

Arm

41.8

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II study to determine the efficacy and safety of PHE885, a BCMA-directed CAR-T cells, manufactured with a new process. CAR-T cells will be investigated as a single agent in relapsed and refractory multiple myeloma

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Biological: PHE885	Phase 2

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) who failed 3 or more different prior 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 100 efficacy evaluable adult patients with relapsed and refractory MM (efficacy evaluable means participants injected with a PHE885 product 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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II, Open Label, Study of PHE885, a B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Relapsed and Refractory Multiple Myeloma

Actual Study Start Date :

Mar 7, 2022

Anticipated Primary Completion Date :

Aug 30, 2023

Anticipated Study Completion Date :

Aug 29, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PHE885 Patients will receive PHE885	Biological: PHE885 Intravenous injection (IV) injection

Arm

Intervention/Treatment

Experimental: PHE885

Patients will receive PHE885

Biological: PHE885

Intravenous injection (IV) injection

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) per Independent Review Committee (IRC) [24 Months]
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'

Secondary Outcome Measures

Complete response rate (CRR) [24 Months]
Percentage of patients with BOR of sCR or CR according to the IMWG criteria
Time to response [24 Months]
Time form PHE885 infusion to the date of first documented response (PR or better)
Duration of Response (DOR) [24 Months]
Time from first documented response (PR or better) until relapse or death due to any cause
Progression free survival (PFS) [24 Months]
Time from PHE885 infusion until progression or death due to any cause
Time to next anti-myeloma treatment (TTNT) [24 Months]
Time from PHE885 infusion until start of new anti-myeloma therapy or death due to any cause
Overall Survival (OS) [24 Months]
Time from PHE885 infusion until death due to any cause
Patient Reported Outcomes (PRO): EORTC-QLQ-C30 [24 months]
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.
Patient Reported Outcomes (PRO): EQ-5D-5L Health Questionnaire [24 months]
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.
Patient Reported Outcomes (PRO): EORTC-QLQ-MY20 [24 months]
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.
Rate of minimal residual disease (MRD) Negativity [24 Months]
Percentage of patients who attain MRD negative status defined at sensitivity level of 1 in 10^5 nucleated cells by next generation sequencing (NGS)
Durability of MRD negativity [24 Months]
Time from the start of undetectable MRD to the time of reappearance of detectable MRD
PHE885 manufacturing success rate [24 Months]
Percentage of enrolled patients for whom PHE885 product was manufactured that met all release specifications
Manufacturing turnaround time [24 months]
Time from pick of cryopreserved material at the clinic or hospital until return to the clinical or hospital
Immunogenicity to PHE885 [24 Months]
Summary of pre-existing and treatment-induced immunogenicity (cellular and humoral) of PHE885
Transgene of PHE885 concentrations over time in peripheral blood and bone marrow [24 Months]
As determined by quantitative polymerase chain reaction (qPCR)
Cellular kinetics parameter: Cmax [24 Months]
The maximum transgene level at Tmax
Cellular kinetics parameter: Tmax [24 Months]
The time to peak transgene level
Cellular kinetics parameter: AUC [24 months]
The Area under the curve of the transgene level

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥18 years of age at the time of informed consent form (ICF) signature
Adult patients with relapsed and refractory multiple myeloma who have received at least 3 prior 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 have documented evidence of disease progression (IMWG criteria)
Must be refractory to the last treatment regimen (defined as progressive disease on or within 60 days measured from last dose of last regimen).
Measurable disease at enrollment as defined by the protocol
Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening
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. Participants who have received prior BCMA -directed bi-speciific antibodies or anti-BCMA antibody drug conjugate.
Prior allogenic stem cell transplantation (SCT) at any time or autologous SCT within 3 months prior to signing informed consent
Plasma cell (PC) leukemia and other plasmacytoid disorders, other than MM
POEMS syndrome
Active central nervous system (CNS) involvement by malignancy
Patients with active neurological auto immune or inflammatory disorders

Other protocol-defined Inclusion/Exclusion may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	VIC	Melbourne	Australia	3004
2	Novartis Investigative Site	Bologna	BO	Italy	40138
3	Novartis Investigative Site	Singapore		Singapore	119228
4	Novartis Investigative Site	Singapore		Singapore	169608
5	Novartis Investigative Site	Salamanca	Castilla Y Leon	Spain	37007