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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05172596
• Other study ID #: CPHE885B12201
• Secondary ID: 2021-003747-22
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 7, 2022
• Est. completion date: December 16, 2025

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 136
• Est. completion date: December 16, 2025
• Est. primary completion date: December 16, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• PHE885
Intravenous (IV) infusion

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Camperdown	New South Wales
Australia	Novartis Investigative Site	VIC	Melbourne
Brazil	Novartis Investigative Site	Salvador	BA
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Canada	Novartis Investigative Site	Calgary	Alberta
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Paris 10
France	Novartis Investigative Site	Poitiers
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Wuerzburg
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki	GR
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Milano	MI
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Sendai city	Miyagi
Saudi Arabia	Novartis Investigative Site	Riyadh
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Manchester
United States	Emory University School of Medicine/Winship Cancer Institute	Atlanta	Georgia
United States	Dana Farber Cancer Institute Main Site	Boston	Massachusetts
United States	Stanford University .	Palo Alto	California
United States	Thomas Jefferson University .	Philadelphia	Pennsylvania
United States	Oregon Health Sciences University .	Portland	Oregon
United States	Fred Hutch Cancer Research	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Saudi Arabia,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Complete response rate (CRR)	Percentage of patients with BOR of sCR or CR according to the IMWG criteria	24 Months
Secondary	Time to response	Time form PHE885 infusion to the date of first documented response (PR or better)	24 Months
Secondary	Duration of Response (DOR)	Time from first documented response (PR or better) until relapse or death due to any cause	24 Months
Secondary	Progression free survival (PFS)	Time from PHE885 infusion until progression or death due to any cause	24 Months
Secondary	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
Secondary	Overall Survival (OS)	Time from PHE885 infusion until death due to any cause	24 Months
Secondary	Durability of Minimal Residual Disease (MRD)negativity	Time from the start of undetectable MRD to the time of reappearance of detectable MRD	24 Months
Secondary	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
Secondary	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
Secondary	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
Secondary	PHE885 manufacturing success rate	Percentage of enrolled patients for whom PHE885 product was manufactured that met all release specifications	24 Months
Secondary	Manufacturing turnaround time	Time from pick of cryopreserved material at the clinic or hospital until return to the clinical or hospital	24 months
Secondary	Transgene of PHE885 concentrations over time in peripheral blood and bone marrow	As determined by quantitative polymerase chain reaction (qPCR)	24 Months
Secondary	Cellular kinetics parameter: Cmax	The maximum transgene level at Tmax	24 Months
Secondary	Cellular kinetics parameter: Tmax	The time to peak transgene level	24 Months
Secondary	Cellular kinetics parameter: AUC	The Area under the curve of the transgene level	24 months
Secondary	Immunogenicity to PHE885	Summary of pre-existing and treatment-induced immunogenicity (cellular and humoral) of PHE885	24 Months