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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: AZD0305; Drug: Elranatamab; Drug: Pomalidomide; Drug: Dexamethasone

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])

• Study Type: Interventional
• Enrollment (Estimated): 226
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Fitzroy, Australia, VIC3065
    • Not yet recruiting
    • Research Site
  • Melbourne, Australia, 3000
    • Recruiting
    • Research Site
  • Nedlands, Australia, 6009
    • Recruiting
    • Research Site
  • Wollongong, Australia, 2500
    • Not yet recruiting
    • Research Site
• Canada
  • Nova Scotia, Canada, B3H 1V7
    • Not yet recruiting
    • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Recruiting
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Not yet recruiting
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Research Site
• China
  • Beijing, China, 100044
    • Recruiting
    • Research Site
  • Changsha, China, 410013
    • Recruiting
    • Research Site
  • Guangzhou, China, 510060
    • Recruiting
    • Research Site
  • Shenyang, China, 110134
    • Recruiting
    • Research Site
• France
  • Lille, France, 59037
    • Recruiting
    • Research Site
  • Nantes, France, 44000
    • Recruiting
    • Research Site
• Germany
  • Essen, Germany, 45147
    • Recruiting
    • Research Site
  • Freiburg im Breisgau, Germany, 79106
    • Withdrawn
    • Research Site
  • Hamburg, Germany, 20246
    • Recruiting
    • Research Site
  • Heidelberg, Germany, 69120
    • Not yet recruiting
    • Research Site
  • Lübeck, Germany, 23538
    • Recruiting
    • Research Site
  • Nuremberg, Germany, 90419
    • Recruiting
    • Research Site
  • Tübingen, Germany, 72076
    • Not yet recruiting
    • Research Site
  • Würzburg, Germany, 97080
    • Recruiting
    • Research Site
• Japan
  • Kashiwa, Japan, 277-8577
    • Recruiting
    • Research Site
  • Nagoya, Japan, 467-8602
    • Recruiting
    • Research Site
  • Yamagata, Japan, 990-9585
    • Recruiting
    • Research Site
• Spain
  • Badalona, Spain, 8916
    • Not yet recruiting
    • Research Site
  • Madrid, Spain, 28027
    • Recruiting
    • Research Site
  • Madrid, Spain, 28041
    • Recruiting
    • Research Site
  • Pamplona, Spain, 31005
    • Recruiting
    • Research Site
  • Salamanca, Spain, 37007
    • Recruiting
    • Research Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • Research Site
    • Irvine, California, United States, 92618
      • Recruiting
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD0305 monotherapy; Module 1: Phase Ia: Dose Escalation Phase Ib: Dose Expansion/Optimization AZD0305 will be administered at specified dose levels.	Drug: AZD0305; AZD0305 Investigational product
Experimental: AZD0305 + Elranatamab; Module2: Phase 1a: Dose escalation and Phase 1b: Backfills, AZD0305 will be administered in combination with elranatamab, following the module-specific dosing.	Drug: AZD0305; AZD0305 Investigational product; Drug: Elranatamab; Module 2 Investigational product
Experimental: AZD0305 + Pomalidomide and Dexamethasone; Module3: Phase 1a: Dose escalation and Phase 1b: Backfills, AZD0305 will be administered in combination with pomalidomide and dexamethasone, following the module-specific dosing.	Drug: AZD0305; AZD0305 Investigational product; Drug: Pomalidomide; Module 3 Standard of Care (background treatment); Drug: Dexamethasone; Module 3 Standard of Care (background treatment)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From time of Informed consent to 30 days post end of treatment
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	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)
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.	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

Outcome Measure	Measure Description	Time Frame
Phase Ia: Objective Response Rate (ORR)	The percentage of patients with a confirmed investigator assessed sCR, CR, VGPR or PR according to IMWG criteria	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	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	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	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	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)	Maximum observed plasma concentration of the study drug	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 to maximum observed plasma concentration of the study drug	From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Phase Ia: Pharmacokinetics of AZD0305: Clearance	A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time	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)	Terminal elimination half-life	From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Phase Ia: Immunogenicity of AZD0305	The number and percentage of participants who develop ADAs	From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Phase Ia: Immunogenicity of elranatamab	The number and percentage of participants who develop ADAs	From the first dose, at predefined intervals until Cycle 24 administration of elranatamab(approximately 2 years)
Phase Ia: MRD negative CR rate	The percentage of patients who achieve a complete response (CR) and have minimal residual disease (MRD) negativity in bone marrow.	From first dose of AZD0305 to progressive disease or death in the absence of disease progression (approximately 2 years)
Phase Ib: Objective Response Rate (ORR)	The percentage of patients with a confirmed investigator assessed sCR, CR, VGPR or PR according to IMWG criteria	From randomization/cohort assignment to progressive disease or Initiation of subsequent MM therapy (approximately 2 years)
Phase Ib: Duration of response (DoR)	The time from date of first response until date of disease progression or death in the absence of disease progression	From randomization/cohort assignment to confirmed progressive disease or death (approximately 2 years)
Phase Ib: Progression free Survival (PFS)	The time from randomization until IMWG defined disease progression or death	From randomization/cohort assignment to progressive disease or death in the absence of disease progression (approximately 2 years)
Phase Ib: Overall Survival (OS)	The time from randomization until death due to any cause	From randomization/cohort assignment to death (approximately 2 years)
Phase Ib: Pharmacokinetics of AZD0305: Area Under the concentration-time curve (AUC)	Area under the plasma concentration-time curve	From randomization/cohort assignment , at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Phase Ib: Pharmacokinetics of AZD0305: Maximum plasma concentration of the study drug (Cmax)	Maximum observed plasma concentration of the study drug	From randomization/cohort assignment , at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Phase Ib: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (tmax)	Time to maximum observed plasma concentration of the study drug	From randomization/cohort assignment , at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Phase Ib: Pharmacokinetics of AZD0305: Clearance	A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time	From randomization/cohort assignment , at predefined intervals throughout the administration of AZD0305 (approximately 2 years
Phase Ib: Pharmacokinetics of AZD0305: Terminal elimination half-life (t 1/2)	Terminal elimination half-life	From randomization/cohort assignment, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Phase Ib: Immunogenicity of AZD0305	The number and percentage of participants who develop ADAs	From randomization/cohort assignment, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Phase Ib: Immunogenicity of elranatamab	The number and percentage of participants who develop ADAs	From the first dose, at predefined intervals until Cycle 24 administration of elranatamab(approximately 2 years)
Phase 1b: MRD negative CR rate	The percentage of patients who achieve a complete response (CR) and have minimal residual disease (MRD) negativity in bone marrow.	From first dose of AZD0305 to progressive disease or death in the absence of disease progression (approximately 2 years)
Complete Response Rate (CRR) - Mod2&3 only	Percentage of participants achieving a confirmed CR or sCR per IMWG criteria.	From first dose of combination treatment to progressive disease or initiation of subsequent multiple myeloma therapy (approximately 2 years)
Pre-Dose Plasma Concentration of Elranatamab (pharmacokinetics - Module 2 only)	Pre-dose Plasma concentrations for elranatamab.	From the first dose of study intervention, at predefined intervals until Cycle 24 administration of elranatamab(approximately 2 years; 1 cycle = 28 days)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2023
• Primary Completion (Estimated): August 16, 2027
• Study Completion (Estimated): August 16, 2027

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Myeloma; MM; ADC; GPRC5D; AZD0305; MMAE
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone; pomalidomide
• Other Study ID Numbers: D7230C00001; 2023-508590-89-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No