NCT06106945

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 efficacy of AZD0305 as monotherapy and in combination with other anticancer agents in participants with MM.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
226

participants targeted

Target at P75+ for phase_1 multiple-myeloma

Timeline
13mo left

Started Dec 2023

Geographic Reach
9 countries

43 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress72%
Dec 2023Aug 2027

First Submitted

Initial submission to the registry

October 11, 2023

Completed
19 days until next milestone

First Posted

Study publicly available on registry

October 30, 2023

Completed
1 month until next milestone

Study Start

First participant enrolled

December 5, 2023

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 16, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 16, 2027

Last Updated

July 13, 2026

Status Verified

July 1, 2026

Enrollment Period

3.7 years

First QC Date

October 11, 2023

Last Update Submit

July 10, 2026

Conditions

Keywords

GPRC5DADCAZD0305Multiple MyelomaMMMMAE

Outcome Measures

Primary Outcomes (3)

  • 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)

  • 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

  • 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 Outcomes (26)

  • Phase Ia: Objective Response Rate (ORR)

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

  • Phase Ia: Duration of response (DoR)

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

  • Phase Ia: Progression free Survival (PFS)

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

  • Phase Ia: Overall Survival (OS)

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

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

    From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)

  • +21 more secondary outcomes

Study Arms (3)

AZD0305 monotherapy

EXPERIMENTAL

Module 1: Phase Ia: Dose Escalation Phase Ib: Dose Expansion/Optimization AZD0305 will be administered at specified dose levels.

Drug: AZD0305

AZD0305 + Elranatamab

EXPERIMENTAL

Module2: Phase 1a: Dose escalation and Phase 1b: Backfills, AZD0305 will be administered in combination with elranatamab, following the module-specific dosing.

Drug: AZD0305Drug: Elranatamab

AZD0305 + Pomalidomide and Dexamethasone

EXPERIMENTAL

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: AZD0305Drug: PomalidomideDrug: Dexamethasone

Interventions

Module 2 Investigational product

AZD0305 + Elranatamab

Module 3 Standard of Care (background treatment)

AZD0305 + Pomalidomide and Dexamethasone

Module 3 Standard of Care (background treatment)

AZD0305 + Pomalidomide and Dexamethasone

AZD0305 Investigational product

AZD0305 + ElranatamabAZD0305 + Pomalidomide and DexamethasoneAZD0305 monotherapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (43)

Research Site

Duarte, California, 91010, United States

RECRUITING

Research Site

Irvine, California, 92618, United States

RECRUITING

Research Site

Atlanta, Georgia, 30322, United States

RECRUITING

Research Site

Boston, Massachusetts, 02215, United States

RECRUITING

Research Site

Ann Arbor, Michigan, 48109, United States

RECRUITING

Research Site

St Louis, Missouri, 63110, United States

WITHDRAWN

Research Site

New York, New York, 10065, United States

RECRUITING

Research Site

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Research Site

Fairfax, Virginia, 22031, United States

RECRUITING

Research Site

Fitzroy, VIC3065, Australia

RECRUITING

Research Site

Melbourne, 3000, Australia

RECRUITING

Research Site

Nedlands, 6009, Australia

RECRUITING

Research Site

Wollongong, 2500, Australia

NOT YET RECRUITING

Research Site

Salvador, 41253-190, Brazil

NOT YET RECRUITING

Research Site

São Paulo, 04537-080, Brazil

NOT YET RECRUITING

Research Site

São Paulo, 05652000, Brazil

NOT YET RECRUITING

Research Site

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Research Site

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Research Site

Toronto, Ontario, M5G 2M9, Canada

NOT YET RECRUITING

Research Site

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Research Site

Nova Scotia, B3H 1V7, Canada

NOT YET RECRUITING

Research Site

Beijing, 100044, China

RECRUITING

Research Site

Changsha, 410013, China

RECRUITING

Research Site

Guangzhou, 510060, China

RECRUITING

Research Site

Shenyang, 110134, China

RECRUITING

Research Site

Lille, 59037, France

RECRUITING

Research Site

Nantes, 44000, France

RECRUITING

Research Site

Essen, 45147, Germany

RECRUITING

Research Site

Freiburg im Breisgau, 79106, Germany

WITHDRAWN

Research Site

Hamburg, 20246, Germany

RECRUITING

Research Site

Heidelberg, 69120, Germany

NOT YET RECRUITING

Research Site

Lübeck, 23538, Germany

RECRUITING

Research Site

Nuremberg, 90419, Germany

RECRUITING

Research Site

Tübingen, 72076, Germany

NOT YET RECRUITING

Research Site

Würzburg, 97080, Germany

RECRUITING

Research Site

Kashiwa, 277-8577, Japan

RECRUITING

Research Site

Nagoya, 467-8602, Japan

RECRUITING

Research Site

Yamagata, 990-9585, Japan

RECRUITING

Research Site

Badalona, 8916, Spain

NOT YET RECRUITING

Research Site

Madrid, 28027, Spain

RECRUITING

Research Site

Madrid, 28041, Spain

RECRUITING

Research Site

Pamplona, 31005, Spain

RECRUITING

Research Site

Salamanca, 37007, Spain

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomideDexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Masking Details
No Masking
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: This protocol has a modular design, with 3 treatment arms/modules. Module 1 will include Phase Ia (Dose escalation), and Phase Ib (Dose expansion/optimization). Module 2 will evaluate AZD0305 in combination with elranatamab at selected dose levels. Module 3 will evaluate AZD0305 in combination with pomalidomide and dexamethasone at selected dose levels.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 11, 2023

First Posted

October 30, 2023

Study Start

December 5, 2023

Primary Completion (Estimated)

August 16, 2027

Study Completion (Estimated)

August 16, 2027

Last Updated

July 13, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, 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.
More information

Locations