Adult participants with relapsed and refractory multiple myeloma 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 and documented evidence of progressive disease per IMWG criteria on the last prior therapy. Participants must be refractory to the last line of therapy. MedDRA version: 21.0 Leve
Conditions
Interventions
Product Name: PHE885
Product Code: PHE885
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: not yet available
Current Sponsor code: PHE885
Other descriptive name: Autologous T cells e
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained prior to any screening procedures. 2. Participants must be =18 years of age at the time of informed consent form (ICF) signature. 3. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at screening. 4. Participant has a previous diagnosis of MM, based on IMWG definitions. 5. Participants who have failed three or more lines of therapy including failing an IMiD (e.g., lenalidomide or pomalidomide), a proteasome inhibitor (e.g., bortezomib, carfilzomib), and an anti-CD38 agent (e.g., daratumumab, isotuximab) and have documented evidence of disease progression (IMWG criteria). • A minimum of 51 participants who have failed 3 therapies will be required among the 100 evaluable participants. Enrollment for participants with 4 or more lines of prior therapy will be closed after the 49th participant to meet this eligibility criteria. 6. Must have received = 1 cycle of treatment for each regimen unless deemed refractory to that regiment (i.e. progressive disease as the best response). 7. Must be refractory to the last treatment regimen (defined as progressive disease on or within 60 days measured from last dose of last regimen). 8. Must have measurable disease defined by at least 1 of the following 3 measurements as per IMWG criteria: • Serum M-protein = 1.0 g/dL OR • Urine M-protein = 200 mg/24 hours OR • Serum free light chain (FLC) = 100 mg/L of involved FLC provided sFLC ratio is abnormal 9. The participant is willing and able to adhere to the procedures and treatments outlined in the protocol. 10. Must have a leukapheresis product of non-mobilized cells accepted for manufacturing. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: 1. Prior administration of a genetically modified cellular product, including prior BCMA CAR-T cell therapy. 2. Participants who have received prior BCMA-directed bi-specific antibodies or anti-BCMA antibody drug conjugate. 3. Hypersensitivity to any product (including its ingredients) to be given to the participant as per the study protocol (e.g., PHE885, tocilizumab and lymphodepleting agents). 4. Prior autologous SCT within 3 months prior to signing informed consent or allogeneic SCT within 3 months prior to signing informed consent. 5. Active Graft-versus-Host Disease (GVHD), grade 2-4 according to the Mount Sinai GvHD International Consortium criteria or requiring systemic treatment. 6. Plasma cell leukemia and other plasmacytoid disorders, non-secretory myeloma without other evidence of measurable disease. 7. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). 8. Active CNS involvement by malignancy. Participants whose CNS involvement was treated with resolved symptoms, provided that local treatment was > 4 weeks before enrollment, are eligible. 9. Participants with active neurological auto immune or inflammatory disorders (e.g., Guillain-Barre Syndrome, Amyotrophic Lateral Sclerosis). 10. Participants with Grade = 3 neuropathy, or residual non-hematologic effects of Grade = 2 from previous therapy (excluding alopecia). 11. Chemotherapy, small molecule targeted antineoplastics, or any concomitant anti-cancer therapies (other than protocol allowed LD chemotherapy) within 2 weeks prior to apheresis or prior to PHE885 injection. 12. For participants that received prior antibodies (e.g., daratumumab, isotuximab, elotuzumab) the washout period is 3 weeks prior to apheresis collection. 13. Radiotherapy within 2 weeks prior to enrollment except localized radiation therapy for lytic bone lesions or plasmacytomas. 14. Investigational medicinal product within the 4 weeks prior to screening or within 5-half-lives of the investigational product, whichever is longer. Note: Investigational therapies must not be used at any time while on study until the first progression following PHE885 injection. 15. Participants receiving systemic steroid therapy or other immunosuppressive drugs unless the conditions outlined in the protocol are met. 16. Previous or concurrent malignancy with the following exceptions: • Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry) • In situ carcinoma treated curativel • A primary malignancy which has been completely resected and in complete remission for = 3 years. 17. Impaired cardiac function or clinically significant cardiac disease, including any of the conditions outlined in the protocol. 18. Inadequate organ function during screening (i.e., within 56 days before the first dose of study treatment) as outlined in the protocol. 19. Presence of active hepatitis B or C as indicated by serology. 20. Human immunodeficiency virus (HIV) positivity as indicated by serology. 21. Clinically significant active infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, etc.). 22. Use of any live vaccines against infectious disease within 6 weeks of PHE885 injection. 23. Serious medical or psychiatric illness likely to interfere with participation in this clinical study. 24. Pregnant or nursing (lactating) women. NOTE: Women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of PHE885 with respect to disease response per independent review committee (IRC) in participants injected with PHE885 ;Secondary Objective: • Assess additional efficacy outcomes including complete response rate (CRR), time to response (TTR), duration of response (DOR), progression-free survival (PFS) per IRC and local investigator assessment • Assess time to next treatment (TTNT) and overall survival (OS) • Evaluate rate of minimal residual disease (MRD) negativity in bone marrow measured by next-generation sequencing (NGS) • Assess durability of MRD negativity • Assess patient reported outcomes (PRO) • Assess the PHE885 manufacturing success rate • Assess manufacturing turnaround time • Assess safety of PHE885 • Assess the cellular kinetics of PHE885 in peripheral blood and bone marrow by qPCR • Assess immunogenicity (humoral and cellular) to PHE885 ;Primary end point(s): Best overall response (BOR) per IRC defined as the best disease response recorded from PHE885 administration until progressive disease or start of new anticancer therapy whichever comes first, with possible values of either stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), progressive disease (PD) or unknown (UNK), according to the International Myeloma Working Group (IMWG) criteria. The summary measure for the primary endpoint is overall response rate (ORR), defined as the proportion of participants with a BOR of PR or better, assessed in the efficacy analysis set (EAS). ;Timepoint(s) of evaluation of this end point: Efficacy interim analysis (6 months after the first 75 pts), Primary analysis (6 months after 100 pts) and Final CSR (24 months after all 100 pts) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • CRR defined as the proportion of participants with BOR of sCR or CR • TTR defined as time from PHE885 administration to the date of first documented response (PR or better) • DOR defined as time from first documented response (PR or better) until relapse or death due to any cause • PFS defined as time from PHE885 administration until progression or death due to any cause • TTNT defined as time from PHE885 administration until start of new anti-myeloma therapy or death due to any cause • OS defined as time from PHE885 administration until death due to any cause • Proportion of participants who attain MRD negative status, defined at sensitivity level of 1 in 10^5 nucleated cells by NGS • Duration from the start of undetectable MRD to the time of reappearance of detectable MRD • Summary scores of PRO measured by EQ-5D-5L, EORTC-QLQ-C30 and EORTC-QLQ-MY20 • Proportion of enrolled participants for whom a PHE885 product was manufactured that met all release specifications • Time from pick up of cryopreserved material at the clinic or hospital until return to the clinic or hospital. • Type, frequency, and severity of adverse events, serious adverse events, adverse events of special interest (AESIs) and laboratory abnormalities • Transgene of PHE885 concentrations over time in peripheral blood and bone marrow determined by quantitative PCR Cellular kinetics parameters: Cmax (maximum serum concentration), Tmax (time to reach Cmax), AUCs and other cellular kinetic parameters • Summary of pre-existing and treatment-induced immunogenicity (cellular and humoral) of PHE885 Correlate levels of pre-existing and treatment-induced immunogenicity with cellular kinetic parameters, safety and efficacy ;Timepoint(s) of evaluation of this end point: Efficacy interim analysis (6 months after the first 75 pts), Primary analysis (6 months after 100 pts) and Final CSR (24 months after all 100 pts) | — |
Countries
Australia, Brazil, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Saudi Arabia, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactInformation&Communication Médicales
Novartis Pharma S.A.S.
Outcome results
None listed