AZD0305 as Monotherapy or in Combination With Anticancer Agents in Participants With 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 efficacy of AZD0305 as monotherapy and in combination with other anticancer agents in participants with MM.

This study will follow a modular protocol design evaluating AZD0305 as monotherapy and in combination with other anticancer agents. The protocol may be amended in the future to incorporate further monotherapy expansion at the recommended Phase 2 dose (RP2D) in Phase II, and/or additional modules investigating AZD0305 in combination with other anticancer agents. The study consists of 3 modules: * Module 1 (AZD0305 monotherapy), * Module 2 (AZD0305 in combination with elranatamab) * Module 3 (AZD0305 in combination with pomalidomide and dexamethasone \[Pd\])

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

226

Conditions

Multiple Myeloma

Interventions

AZD0305DRUG

AZD0305 Investigational product

ElranatamabDRUG

Module 2 Investigational product

PomalidomideDRUG

Module 3 Standard of Care (background treatment)

Dexamethasone

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key 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 performance status of ≤ 2 in module 1, or 0 or 1 in modules 2 and 3; * 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 measurable disease criteria for Serum M-Protein, Urine M-protein, and Serum immunoglobulin free light chains as specified in the relevant module of the CSP; * Adequate organ and bone marrow function assessment at screening according to the hematological, hepatic, and renal parameters listed in the CSP as relevant to each module; * Participants must have received at least 3 prior lines of treatment in module 1, or 1-3 prior lines in modules 2 and 3, with additional module-specific requirements related to prior lines of therapy The above is a summary of key criteria, other inclusion criteria details may apply Key Exclusion Criteria: * Amyloidosis, plasma cell leukemia, Waldenstrom Macroglobulinemia, Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin Syndrome, or Smoldering Multiple Myeloma (compliant with WHO criteria); * Participants exhibiting clinical signs of central nervous system involvement of MM; * Participants with known COPD, or previous history of ILD/pneumonitis; * 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; * Participants with a history of prior malignancy other than MM within 3 years prior to first dose of study intervention. some exceptions apply; * Participants with previous history of active JC virus infection resulting in PML; * Participants with a known hypersensitivity to AZD0305 or any of the excipients of the product or to any of the drugs included in the respective modules or who experienced Grade 3 or higher hypersensitivity to prior monoclonal antibody therapy; * Participants who have uncontrolled severe illness including but not limited to ongoing active infection requiring therapeutic antibiotics and/or other administration The above is a summary of key criteria, other exclusion criteria details may apply

Locations (43)

Outcomes

Primary Outcomes

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

A DLT is any toxicity occuring from the ﬁrst dose of AZD0305 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 AZD0305 until the end of Cycle 1. Cycle 1 (the DLT assessment period is 21 days for Module 1 Group A and 28 days for Module 1 Group B, Module 2, and Module 3)

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

Frequency of dose modifications, dose delays, and treatment discontinuations due to AEs (Module 2 and Module 3)

Number and percentage of participants with dose modifications, dose delays, and permanent discontinuations due to adverse events (for AZD0305 and combination agent\[s\], as applicable), per protocol-defined dose modification rules.

Time frame: From first dose of study treatment until End of treatment (EOT), assessed up to approximately 2 years (each cycle is 28 days)

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

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Module 3 Standard of Care (background treatment)

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

WITHDRAWN

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

Fitzroy, Australia

RECRUITING

...and 33 more locations

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)

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