Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, BCMA, CAR T, CD19, AZD0120
Brief summary
This trial is a Phase 1b/2, open-label, multicenter study of AZD0120, a CD19/BCMA dual CAR T-cell therapy, in adult subjects with relapsed/refractory multiple myeloma.
Detailed description
Phase 1b aims to evaluate the safety, tolerability, pharmacokinetic characteristics, pharmacodynamic effect, and immunogenicity in subjects with relapsed/refractory multiple myeloma and determine the recommended Phase 2 dose of AZD0120. Phase II aims to evaluate the efficacy of AZD0120, and to further characterize the safety, pharmacodynamic effects, immunogenicity, and changes in health-related quality of life parameters in subjects with relapsed/refractory multiple myeloma.
Interventions
BIOLOGICALAZD0120
AZD0120 is a BCMA/CD19 dual CAR T product under investigation for the treatment of participants with RRMM.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
AZD0120 will be administered by infusion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥18 years of age at the time of consent. * ECOG performance status of 0 or 1. * Documented diagnosis of MM per IMWG diagnostic criteria. * Participant must have received at least 3 prior lines of therapy, which include a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody. * Have documented evidence of progressive disease per IMWG criteria. * Participant must have measurable disease at screening. * Participant must have adequate bone marrow and organ function (hematological, hepatic and renal) demonstrated at screening.
Exclusion criteria
: * Participant has a history of significant toxicity during prior CAR T-cell therapy and T-cell engaging therapy. * Participant has a history of a prior non-hematologic malignancy, unless the participant has been disease-free with no evidence of recurrence for ≥ 2 years. Some exceptions may apply. * Participant has significant cardiac, neurological, or psychiatric conditions. * Any other significant medical conditions such as: * Serious active or uncontrolled infection * Active autoimmune disease or a history of autoimmune disease within 2 years * Active plasma cell leukemia at the time of screening * Clinical evidence of dementia or altered mental status, or stroke, intracranial haemorrhage, or seizure within 6 months before signing informed consent form (ICF). * Known active or prior history of central nervous system involvement or exhibits clinical signs of meningeal involvement of MM. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Adverse Events (AEs) | Through study completion, a minimum of 2 years. | The incidence and severity of AEs. |
| Phase 1b: Dose-Limiting Toxicities (DLTs) | 28 days | The DLT evaluation period is defined as the first 28 days after infusion. |
| Phase 2: Objective Response Rate (ORR) | Through study completion, a minimum of 2 years. | Defined as the proportion of participants who achieved partial response (PR) or better by the International Myeloma Working Group (IMWG) response criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b and 2: Complete response rate (CRR) | Through study completion, a minimum of 2 years. | Defined as the proportion of participants who achieved complete response (CR) or better per International Myeloma Working Group (IMWG) criteria. |
| Phase 1b and 2: Time to response (TTR) | Through study completion, a minimum of 2 years. | Defined as the time between date of the initial infusion of AZD0120 and the first efficacy evaluation that the participant has met all criteria for partial response (PR) or better. |
| Phase 1b: Objective Response Rate (ORR) | Through study completion, a minimum of 2 years. | Defined as the proportion of participants who achieved PR or better by IMWG response criteria. |
| Phase 1b and 2: Minimal Residual Disease (MRD) negative Complete Response (CR) rate | Through study completion, a minimum of 2 years. | Defined as the proportion of participants who achieve CR or better response with MRD negativity per IMWG criteria. |
| Phase 1b and 2: Minimal Residual Disease (MRD) negative Complete Response (CR) rate at 12 months | 12 months | Defined as the proportion of participants who achieve CR or better response with MRD negativity per IMWG criteria at 12 months. |
| Phase 1b and 2: Duration of response (DOR) | Through study completion, a minimum of 2 years. | Defined among responders as the time from the date of initial documentation of an objective response (overall response of PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria, or death due to any cause, whichever occurs first. |
| Phase 1b and 2: Progression-free survival (PFS) | Through study completion, a minimum of 2 years. | Defined as the time from the date of the initial infusion of AZD0120 to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first. |
| Phase 1b and 2: Overall survival (OS) | Through study completion, a minimum of 2 years. | Defined as the time from the date of the initial infusion of AZD0120 to the date of the subject's death. |
| Phase 2: Adverse Events (AEs) | Through study completion, a minimum of 2 years. | Further characterization of the safety of AZD0120 by measuring the incidence and severity of AEs. |
| Ph1b and 2: Pharmacokinetics - AUC | Through study completion, a minimum of 2 years. | Area under the concentration time-curve of AZD0120 CAR transgene copies. |
| Ph1b and 2: Pharmacokinetics - Clast | Through study completion, a minimum of 2 years. | Last quantifiable AZD0120 CAR transgene copies. |
| Ph1b and 2: Pharmacokinetics - Cmax | Through study completion, a minimum of 2 years. | Maximum AZD0120 CAR transgene copies. |
| Ph1b and 2: Pharmacokinetics - Tlast | Through study completion, a minimum of 2 years. | Time to last quantifiable AZD0120 CAR transgene copies. |
| Ph1b and 2: Pharmacokinetics - Tmax | Through study completion, a minimum of 2 years | Time to reach maximum AZD0120 CAR transgene copies. |
| Ph1b and 2: Humoral Immunogenicity | Through study completion, a minimum of 2 years. | Serum samples will be analyzed for anti-drug antibodies (ADA) against AZD0120 using a validated immunoassay. Incidence and prevalence of treatment-emergent ADA will be summarized, with descriptive analyses of associations with pharmacokinetics, efficacy, and safety. |
| Phase 2: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire IL355 (EORTC IL355) | Through study completion, a minimum of 2 years. | Changes from baseline in EORTC IL355 to assess the bone pain and other aspects of function. |
| Phase 2: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC IL356 | Through study completion, a minimum of 2 years. | Changes from baseline in EORTC IL356 to assess the symptomatic toxicities and physical functioning. |
Countries
United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed