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

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ClinicalTrials.gov Identifier: NCT06106945
Recruitment Status : Recruiting
First Posted : October 30, 2023
Last Update Posted : April 30, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: AZD0305 Phase 1 Phase 2

Detailed Description:

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. Subjects will be administered AZD0305 intravenously.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: This protocol has a modular design, with the potential for future treatment arms, study parts, or modules to be added via protocol amendments. Module 1 will include Phase Ia (Dose escalation), and Phase Ib (Dose expansion/optimization).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Modular Phase I/II, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Lmmunogenicity, Pharmacodynamics, and Preliminary Efficacy of AZD0305 as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : December 5, 2023
Estimated Primary Completion Date : November 11, 2025
Estimated Study Completion Date : November 11, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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Arm Intervention/treatment
Experimental: AZD0305 monotherapy

Module 1:

Phase Ia: Dose Escalation Phase Ib: Dose Expansion/Optimization AZD0305 will be prescribed at specified dose levels.

 Drug: AZD0305
AZD0305


Outcome Measures
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Primary Outcome Measures :
  1. Occurrence of dose-limiting toxicity (DLT), as defined in the protocol (Phase Ia dose escalation only) [ Time Frame: From first dose of study treatment until the end of Cycle 1 ]
    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

  2. 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 ]
    Number of patients with adverse events and serious adverse events by system organ class and preferred term


Secondary Outcome Measures :
  1. 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) ]
    The percentage of patients with a confirmed investigator assessed sCR, CR, VGPR or PR according to IMWG criteria

  2. Phase Ia: Duration of response (DoR) [ Time Frame: From the first documented response to confirmed progressive disease or death (approximately 2 years) ]
    The time from the date of first response until date of disease progression or death in the absence of disease progression

  3. 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) ]
    The time from first dose until IMWG defined disease progression or death

  4. Phase Ia: Overall Survival (OS) [ Time Frame: From first dose of AZD0305 to death (approximately 2 years) ]
    The time from the date of the first dose of study treatment until death due to any cause

  5. 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) ]
    Area under the plasma concentration-time curve

  6. 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) ]
    Maximum observed plasma concentration of the study drug

  7. 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) ]
    Time to maximum observed plasma concentration of the study drug

  8. 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) ]
    A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time

  9. 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) ]
    Terminal elimination half-life

  10. 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) ]
    The number and percentage of participants who develop ADAs

  11. Phase Ib: Objective Response Rate (ORR) [ Time Frame: From randomization to progressive disease or Initiation of subsequent MM therapy (approximately 2 years) ]
    The percentage of patients with a confirmed investigator assessed sCR, CR, VGPR or PR according to IMWG criteria

  12. Phase Ib: Duration of response (DoR) [ Time Frame: From randomization to confirmed progressive disease or death (approximately 2 years) ]
    The time from date of first response until date of disease progression or death in the absence of disease progression

  13. Phase Ib: Progression free Survival (PFS) [ Time Frame: From randomization to progressive disease or death in the absence of disease progression (approximately 2 years) ]
    The time from randomization until IMWG defined disease progression or death

  14. Phase Ib: Overall Survival (OS) [ Time Frame: From randomization to death (approximately 2 years) ]
    The time from randomization until death due to any cause

  15. Phase Ib: Pharmacokinetics of AZD0305: Area Under the concentration-time curve (AUC) [ Time Frame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years) ]
    Area under the plasma concentration-time curve

  16. Phase Ib: Pharmacokinetics of AZD0305: Maximum plasma concentration of the study drug (Cmax) [ Time Frame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years) ]
    Maximum observed plasma concentration of the study drug

  17. Phase Ib: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (tmax) [ Time Frame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years) ]
    Time to maximum observed plasma concentration of the study drug

  18. Phase Ib: Pharmacokinetics of AZD0305: Clearance [ Time Frame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years ]
    A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time

  19. Phase Ib: Pharmacokinetics of AZD0305: Terminal elimination half-life (t 1/2) [ Time Frame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years) ]
    Terminal elimination half-life

  20. Phase Ib: Immunogenicity of AZD0305 [ Time Frame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years) ]
    The number and percentage of participants who develop ADAs


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06106945


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, California
Research Site Recruiting
Duarte, California, United States, 91010
Research Site Recruiting
Irvine, California, United States, 92618
United States, Michigan
Research Site Not yet recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Research Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Research Site Not yet recruiting
New York, New York, United States, 10065
United States, Pennsylvania
Research Site Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
Research Site Not yet recruiting
Fairfax, Virginia, United States, 22031
Australia
Research Site Recruiting
Melbourne, Australia, 3000
Research Site Recruiting
Perth, Australia, WA 6009
Canada, Ontario
Research Site Not yet recruiting
Hamilton, Ontario, Canada, L8V 5C2
Canada, Quebec
Research Site Not yet recruiting
Montreal, Quebec, Canada, H4A 3J1
China
Research Site Not yet recruiting
Beijing, China, 100044
Germany
Research Site Withdrawn
Freiburg, Germany, 79106
Research Site Not yet recruiting
Hamburg, Germany, 20246
Research Site Not yet recruiting
Lübeck, Germany, 23538
Research Site Not yet recruiting
Nürnberg, Germany, 90419
Research Site Not yet recruiting
Würzburg, Germany, 97080
Japan
Research Site Not yet recruiting
Kashiwa, Japan, 277-8577
Research Site Recruiting
Nagoya-shi, Japan, 467-8602
Spain
Research Site Not yet recruiting
Madrid, Spain, 28041
Research Site Not yet recruiting
Pamplona, Spain, 31005
Research Site Not yet recruiting
Salamanca, Spain, 37007
Sponsors and Collaborators
AstraZeneca
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT06106945    
Other Study ID Numbers: D7230C00001
2023-508590-89-00 ( Other Identifier: EU CT Number )
First Posted: October 30, 2023    Key Record Dates
Last Update Posted: April 30, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
GPRC5D
ADC
AZD0305
 Relapsed Refractory Multiple Myeloma
RRMM
MMAE
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
 Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases