Clinical trial NCT05172596: PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
B-cell maturation antigen
BCMA
BCMA-directed
chimeric antigen receptor
CAR-T
PHE885
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-12-29
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

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) 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR) per Independent Review Committee (IRC) in Efficacy Analysis Set
timeFrame: 24 Months
Secondary outcomes:
measure: Key Secondary End point: MRD Negativity rate in Bone Marrow
timeFrame: 24 months
measure: Complete response rate (CRR)
timeFrame: 24 Months
measure: Time to response
timeFrame: 24 Months
measure: Duration of Response (DOR)
timeFrame: 24 Months
measure: Progression free survival (PFS)
timeFrame: 24 Months
measure: Time to next anti-myeloma treatment (TTNT)
timeFrame: 24 Months
measure: Overall Survival (OS)
timeFrame: 24 Months
measure: Durability of Minimal Residual Disease (MRD)negativity
timeFrame: 24 Months
measure: Patient Reported Outcomes (PRO): EQ-5D-5L Health Questionnaire
timeFrame: 24 months
measure: Patient Reported Outcomes (PRO): EORTC-QLQ-C30
timeFrame: 24 months
measure: Patient Reported Outcomes (PRO): EORTC-QLQ-MY20
timeFrame: 24 months
measure: PHE885 manufacturing success rate
timeFrame: 24 Months
measure: Manufacturing turnaround time
timeFrame: 24 months
measure: Transgene of PHE885 concentrations over time in peripheral blood and bone marrow
timeFrame: 24 Months
measure: Cellular kinetics parameter: Cmax
timeFrame: 24 Months
measure: Cellular kinetics parameter: Tmax
timeFrame: 24 Months
measure: Cellular kinetics parameter: AUC
timeFrame: 24 months
measure: Immunogenicity to PHE885
timeFrame: 24 Months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Emory University School of Medicine-Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Seattle
country: United States
facility: Fred Hutch Cancer Research
state: Washington
city: Camperdown
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Lille
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris 10
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: Attiki
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kyoto-city
country: Japan
facility: Novartis Investigative Site
state: Kyoto
city: Sendai city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Riyadh
country: Saudi Arabia
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: