AZD0305 as Monotherapy or in Combination With Anticancer Agents in Participants With Relapsed/Refractory Multiple Myeloma

Phase 2RecruitingNCT06106945

AstraZeneca226 enrolled

Overview

This is a Phase I/II, modular, open-label, multicenter, dose escalation, and dose expansion/optimization study to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary efficacy of AZD0305 in participants with RRMM. This study will follow a modular protocol design evaluating AZD0305 as monotherapy and in combination with other anticancer agents. The study includes dose escalation and dose expansion phases. This study will enroll subjects with RRMM who received at least 3 prior lines of treatment including at least one proteasome inhibitor (PI), one immunomodulator (IMiD), and an anti-CD38 antibody.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

226

Conditions

Multiple Myeloma

Interventions

AZD0305DRUG

AZD0305

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Principal Inclusion Criteria: * Participants must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place. * Eastern Cooperative Oncology group (ECOG) performance status of ≤ 2. * Documentation of Multiple Myeloma (MM) as defined by International Myeloma Working Group (IMWG) Diagnostic Criteria for Multiple Myeloma. Site should ensure that Multiple Myeloma diagnosis is confirmed in accordance with the IMWG Diagnostic Criteria. * Participants must have one or more of the following measurable disease criteria: 1. Serum M-protein level ≥ 0.5 g/dL. 2. Urine M-protein level ≥ 200 mg/24h. 3. Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio. * Adequate organ and bone marrow function assessment at screening according to the hematological, hepatic, and renal parameters listed in the CSP. * Participants must have received at least 3 prior lines of treatment which include a proteasome inhibitor (e.g., bortezomib), an immunomodulator (e.g., lenalidomide), and an anti-CD38 antibody (e.g., daratumumab). Principal Exclusion Criteria: * Participants exhibiting clinical signs of central nervous system involvement of MM. * Participants with known COPD, or previous history of ILD. * Participants with known moderate or severe persistent asthma within the past 5 years, or uncontrolled asthma of any classification. * Participants who have severe cardiovascular disease which is not adequately controlled. * Participants who have a history of immunodeficiency disease. * Participants with peripheral neuropathy ≥ Grade 2. * Primary refractory MM. * Participants who have previously received anti-GPRC5D or MMAE-containing treatment. * Participants who have previously received allogenic stem cell transplant, or participant has received autologous stem cell transplant within 3 months before the first dose of study intervention.

Locations (36)

Outcomes

Primary Outcomes

Occurrence of dose-limiting toxicity (DLT), as defined in the protocol (Phase Ia dose escalation only)

A DLT is defined as any toxicity that occurs from the first dose of study treatment up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation and which includes, any death not clearly due to the underlying disease or extraneous causes, pre-defined haematological and non-haematological toxicities

Time frame: From first dose of study treatment until the end of Cycle 1

Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number of patients with adverse events and serious adverse events by system organ class and preferred term

Time frame: From time of Informed consent to 30 days post end of treatment

Secondary Outcomes

Phase Ia: Objective Response Rate (ORR)

The percentage of patients with a confirmed investigator assessed sCR, CR, VGPR or PR according to IMWG criteria

Time frame: From first dose of AZD0305 to progressive disease or Initiation of subsequent MM therapy (approximately 2 years)

Phase Ia: Duration of response (DoR)

The time from the date of first response until date of disease progression or death in the absence of disease progression

Time frame: From the first documented response to confirmed progressive disease or death (approximately 2 years)

Phase Ia: Progression free Survival (PFS)

The time from first dose until IMWG defined disease progression or death

Time frame: From first dose of AZD0305 to progressive disease or death in the absence of disease progression (approximately 2 years)

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

Duarte, California, United States

RECRUITING

Research Site

Irvine, California, United States

RECRUITING

Research Site

Atlanta, Georgia, United States

RECRUITING

Research Site

Boston, Massachusetts, United States

RECRUITING

Research Site

Ann Arbor, Michigan, United States

RECRUITING

Research Site

St Louis, Missouri, United States

RECRUITING

Research Site

New York, New York, United States

RECRUITING

Research Site

Philadelphia, Pennsylvania, United States

RECRUITING

Research Site

Fairfax, Virginia, United States

RECRUITING

Research Site

Melbourne, Australia

RECRUITING

...and 26 more locations

Phase Ia: Overall Survival (OS)

The time from the date of the first dose of study treatment until death due to any cause

Time frame: From first dose of AZD0305 to death (approximately 2 years)

Phase Ia: Pharmacokinetics of AZD0305: Area Under the concentration-time curve (AUC)

Area under the plasma concentration-time curve