AZD0120 in Relapsed/Refractory Multiple Myeloma (DURGA-1)

Phase 2RecruitingNCT05850234

AstraZeneca232 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

232

Conditions

Relapsed/Refractory Multiple Myeloma

Interventions

AZD0120BIOLOGICAL

AZD0120 is a BCMA/CD19 dual CAR T product under investigation for the treatment of participants with RRMM.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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/Exclusion criteria apply.

Locations (36)

Outcomes

Primary Outcomes

Phase 1b: Adverse Events (AEs)

The incidence and severity of AEs.

Time frame: Through study completion, a minimum of 2 years.

Phase 1b: Dose-Limiting Toxicities (DLTs)

The DLT evaluation period is defined as the first 28 days after infusion.

Time frame: 28 days

Phase 2: Objective Response Rate (ORR)

Defined as the proportion of participants who achieved partial response (PR) or better by the International Myeloma Working Group (IMWG) response criteria.

Time frame: Through study completion, a minimum of 2 years.

Secondary Outcomes

Phase 1b and 2: Complete response rate (CRR)

Defined as the proportion of participants who achieved complete response (CR) or better per International Myeloma Working Group (IMWG) criteria.

Time frame: Through study completion, a minimum of 2 years.

Phase 1b and 2: Time to response (TTR)

Defined as the time between date of apheresis and the first efficacy evaluation that the participant has met all criteria for partial response (PR) or better.

Time frame: Through study completion, a minimum of 2 years.

Phase 1b: Objective Response Rate (ORR)

Defined as the proportion of participants who achieved PR or better by IMWG response criteria.

Time frame: Through study completion, a minimum of 2 years.

Phase 1b and 2: Minimal Residual Disease (MRD) negative Complete Response (CR) rate

Defined as the proportion of participants who achieve CR or better response with MRD negativity per IMWG criteria.

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

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Research Site

Birmingham, Alabama, United States

RECRUITING

Research Site

Phoenix, Arizona, United States

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Research Site

La Jolla, California, United States

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Research Site

Los Angeles, California, United States

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Research Site

San Francisco, California, United States

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Research Site

Aurora, Colorado, United States

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Research Site

Denver, Colorado, United States

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Research Site

Jacksonville, Florida, United States

RECRUITING

Research Site

Miami, Florida, United States

RECRUITING

Research Site

Tampa, Florida, United States

RECRUITING

...and 26 more locations

Time frame: Through study completion, a minimum of 2 years.

Phase 1b and 2: Minimal Residual Disease (MRD) negative Complete Response (CR) rate at 12 months

Defined as the proportion of participants who achieve CR or better response with MRD negativity per IMWG criteria at 12 months.

Time frame: 12 months

Phase 1b and 2: Duration of response (DOR)

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.

Time frame: Through study completion, a minimum of 2 years.

Phase 1b and 2: Progression-free survival (PFS)

Defined as the time from the date of apheresis to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.

Time frame: Through study completion, a minimum of 2 years.

Phase 1b and 2: Overall survival (OS)

Defined as the time from the date of apheresis to the date of the subject's death.

Time frame: Through study completion, a minimum of 2 years.

Phase 2: Adverse Events (AEs)

Further characterization of the safety of AZD0120 by measuring the incidence and severity of AEs.

Time frame: Through study completion, a minimum of 2 years.

Ph1b and 2: Pharmacokinetics - AUC

Area under the concentration time-curve of AZD0120 CAR transgene copies.

Time frame: Through study completion, a minimum of 2 years.

Ph1b and 2: Pharmacokinetics - Clast

Last quantifiable AZD0120 CAR transgene copies.

Time frame: Through study completion, a minimum of 2 years.

Ph1b and 2: Pharmacokinetics - Cmax

Maximum AZD0120 CAR transgene copies.

Time frame: Through study completion, a minimum of 2 years.

Ph1b and 2: Pharmacokinetics - Tlast

Time to last quantifiable AZD0120 CAR transgene copies.

Time frame: Through study completion, a minimum of 2 years.

Ph1b and 2: Pharmacokinetics - Tmax

Time to reach maximum AZD0120 CAR transgene copies.

Time frame: Through study completion, a minimum of 2 years

Ph1b and 2: Humoral Immunogenicity

Prevalence and incidence of anti-drug antibodies (ADAs) against AZD0120 and the impact on PK, efficacy, and safety, as data allow.

Time frame: Through study completion, a minimum of 2 years.

Phase 2: Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) IL355 Bone Pain and Health-Related Quality of Life Scale Scores

Change from baseline in patient-reported bone pain and health-related quality of life, as assessed using the European Organization for Research and Treatment of Cancer Item Library 355 (EORTC IL355), including the QL2 scale.

Time frame: Through study completion, a minimum of 2 years.

Phase 2: Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) IL356 Physical Function and Fatigue Subscale Scores

Changes from baseline in patient-reported physical function and fatigue, as assessed using the European Organization for Research and Treatment of Cancer Item Library 356 (EORTC IL356).

Time frame: Through study completion, a minimum of 2 years.