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

Official title

A Modular Phase I/II, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics, and Preliminary Efficacy of AZD0305 as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Multiple Myeloma

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.

Detailed description

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 \[Pd\])

Interventions

• Drug AZD0305
  AZD0305 Investigational product
• Drug Elranatamab
  Module 2 Investigational product
• Drug Pomalidomide
  Module 3 Standard of Care (background treatment)
• Drug Dexamethasone
  Module 3 Standard of Care (background treatment)

Primary outcome measures

• Occurrence of dose-limiting toxicity (DLT), as defined in the protocol (Phase Ia dose escalation only) [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) [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) [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 outcome measures (12)

• Phase Ia: Objective Response Rate (ORR) [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) [Time frame: From the first documented response to confirmed progressive disease or death (approximately 2 years)]
• Phase Ia: Progression free Survival (PFS) [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) [Time frame: From first dose of AZD0305 to death (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Area Under the concentration-time curve (AUC) [Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Maximum plasma concentration of the study drug (Cmax) [Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (tmax) [Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Clearance [Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Terminal elimination half-life (t 1/2) [Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Immunogenicity of AZD0305 [Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Immunogenicity of elranatamab [Time frame: From the first dose, at predefined intervals until Cycle 24 administration of elranatamab(approximately 2 years)]
• Phase Ia: MRD negative CR rate [Time frame: From first dose of AZD0305 to progressive disease or death in the absence of disease progression (approximately 2 years)]

Eligibility criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 9 centers

• Research Site — Duarte
• Research Site — Irvine
• Research Site — Atlanta
• Research Site — Boston
• Research Site — Ann Arbor
• Research Site — St Louis
• Research Site — New York
• Research Site — Philadelphia
• … and 1 more center

Germany · 8 centers

• Research Site — Essen
• Research Site — Freiburg im Breisgau
• Research Site — Hamburg
• Research Site — Heidelberg
• Research Site — Lübeck
• Research Site — Nuremberg
• Research Site — Tübingen
• Research Site — Würzburg

Canada · 5 centers

• Research Site — Hamilton
• Research Site — Ottawa
• Research Site — Toronto
• Research Site — Montreal
• Research Site — Nova Scotia

Spain · 5 centers

• Research Site — Badalona
• Research Site — Madrid
• Research Site — Madrid
• Research Site — Pamplona
• Research Site — Salamanca

Australia · 4 centers

• Research Site — Fitzroy
• Research Site — Melbourne
• Research Site — Nedlands
• Research Site — Wollongong

China · 4 centers

• Research Site — Beijing
• Research Site — Changsha
• Research Site — Guangzhou
• Research Site — Shenyang

Brazil · 3 centers

• Research Site — Salvador
• Research Site — São Paulo
• Research Site — São Paulo

Japan · 3 centers

• Research Site — Kashiwa
• Research Site — Nagoya
• Research Site — Yamagata

France · 2 centers

• Research Site — Lille
• Research Site — Nantes

Identifiers

NCT: NCT06106945 · D7230C00001 · 2023-508590-89-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗