This is a randomised, multicentre, controlled, open-label, Phase III global study comparing the efficacy and safety of standard induction regimens (IsaVRd and DRd) followed by AZD0120 versus standard induction regimens followed by continuous therapy (IsaRd and DRd) in participants with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT) as initial therapy.
The primary objective is to demonstrate the superiority of IsaVRd or DRd induction followed by a single administration of AZD0120 compared to IsaVRd or DRd induction followed by continuous IsaRd or DRd in terms of progression-free survival (PFS) according to IMWG 2016 criteria, and as assessed by Blinded Independent Central Review (BICR) and miminal residual disease (MRD) negative complete response (CR) rate at 9 months post-randomisation in participants with NDMM who are ineligible to receive ASCT as initial therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
750
AZD0120, is a BCMA/CD19 dual CAR T-cell product, which is administered intravenously.
Induction, optional bridging and continuous therapy.
Induction, optional bridging and continuous therapy.
PFS in NDMM who are ineligible to receive ASCT is measured to demonstrate the superiority of IsaVRd or DRd induction followed by AZD0120 compared to IsaVRd or DRd induction followed by continuous DRd or IsaRd.
PFS: defined as time from randomisation until progression according to IMWG 2016 criteria as assessed by BICR, or death due to any cause, whichever occurs first.
Time frame: Up to 9 years.
MRD negative CR rate at 9M in NDMM who are ineligible to receive ASCT is measured to demonstrate the superiority of IsaVRd or DRd induction followed by AZD0120 compared to IsaVRd or DRd induction followed by continuous DRd or IsaRd
MRD negative CR rate at 9 months: defined as the proportion of participants with MRD negative status (at threshold of 10-5) and have a response of CR or sCR (according to the IMWG 2016 criteria) as assessed by BICR at 9 months (± 3 months) from randomisation before initiation of subsequent anti-myeloma therapy.
Time frame: Up to 9 years.
Complete Response Rate
The proportion of participants who achieved CR or better according to IMWG 2016 criteria, as assessed by BICR
Time frame: Up to 9 years.
Overall Survival
Time from randomisation until date of death due to any cause
Time frame: Up to 9 years.
Number and percentage of participants with adverse events as graded by CTCAE v6 and ASTCT Consensus Grading criteria
Adverse Event Incidence
Time frame: Up to 9 years.
Concentration of Circulating CAR-T+ Cells in Peripheral Blood
Quantification of circulating CAR-T+ cell levels by measuring CAR transgene in peripheral blood and CK parameters of AZD0120 will be measured to characterise the cellular kinetics of AZD0120 in blood.
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Induction, optional bridging and continuous therapy.
Induction, optional bridging and continuous therapy.
Induction therapy.
Lymphodepletion
Lymphodepletion
Research Site
Gilbert, Arizona, United States
NOT_YET_RECRUITINGResearch Site
Phoenix, Arizona, United States
NOT_YET_RECRUITINGResearch Site
Tucson, Arizona, United States
NOT_YET_RECRUITINGResearch Site
Orange, California, United States
NOT_YET_RECRUITINGResearch Site
Santa Monica, California, United States
NOT_YET_RECRUITINGResearch Site
Aurora, Colorado, United States
NOT_YET_RECRUITINGResearch Site
Denver, Colorado, United States
NOT_YET_RECRUITINGResearch Site
New Haven, Connecticut, United States
NOT_YET_RECRUITINGResearch Site
Coral Gables, Florida, United States
NOT_YET_RECRUITINGResearch Site
Tampa, Florida, United States
NOT_YET_RECRUITING...and 114 more locations
Time frame: Up to 9 years.
Number and percentage of participants with incidence of ADAs against AZD0120
Assessment humoral immunogenicity of AZ0120 based on incidence of ADAs.
Time frame: Up to 9 years.
Patient Reported Outcomes
Change from baseline in bone pain severity measured by the European Organisation for Research and Treatment of Cancer Item Library 469 single bone pain item (EORTC IL469 - score range 0 - 100, with higher scores indicating worse bone pain) in participants with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation as initial therapy.
Time frame: Up to 9 years.
Patient Reported Outcomes
Change from baseline in fatigue severity, physical functioning, and global health status/quality of life measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 fatigue, physical functioning, and global health status/quality of life scales (EORTC QLQ-C30 - score range 0 to 100; higher scores indicate worse fatigue, better physical functioning, and better general health status/quality of life) in participants with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation as initial therapy.
Time frame: Up to 9 years.
Overall Response Rate
Proportion of participants who achieved PR or better according to IMWG 2016 criteria
Time frame: Up to 9 years
Duration of Response
Time from first documented confirmed response (PR or better) until date of documented PD per IMWG 2016 criteria or death due to any cause, whichever occurs first.
Time frame: Up to 9 years
Time to Response
Time from randomisation until the date of first documented objective response (PR or better), as assessed per IMWG 2016 criteria.
Time frame: Up to 9 years
MRD negative CR rate
Proportion of participants who have MRD negative status and have a response of CR or sCR (according to the IMWG 2016 criteria) at any time after the date of randomisation and before initiation of subsequent therapy.
Time frame: Up to 9 years
Rate of sustained MRD negative CR
Proportion of participants who have achieved MRD negative status and have a response of CR or sCR
Time frame: Up to 9 years
Progression Free Survival 2 (PFS2)
Time from randomisation to progression on next line of therapy, as assessed by Investigator, or death due to any cause, whichever occurs first
Time frame: Up to 9 years