A trial to learn if AZD0305 alone and in combination with other cancer treatments is safe and works in adults with multiple myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Jun 2024 → ongoing

Decision date (initial)

2024-09-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-508590-89-00

ClinicalTrials.gov

NCT06106945

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Therapy, Pharmacodynamic, Pharmacokinetic, Efficacy, Safety

To assess the safety and tolerability and determine the Recommended Phase 2 Dose (RP2D) of AZD0305 as monotherapy and in combination with other anticancer agents in participants with MM.
This is the core primary objective of the study, module specific primary objectives are available within the CSP

Secondary objectives 4

1. To estimate the preliminary efficacy of AZD0305 as monotherapy and in combination with other anticancer agents in participants with MM.
2. To evaluate the PK characteristics of AZD0305 as monotherapy and in combination with other anticancer agents in participants with MM.
3. To assess the immunogenicity of AZD0305 as monotherapy and in combination with other anticancer agents in participants with MM.
4. These are the core secondary objectives of the study, module-specific secondary objectives are available within the CSP

Conditions and MedDRA coding

Multiple Myeloma

Study design 3 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000025-PIP74-32

Plan to share 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 Vivli.org. 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. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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.
2. Eastern Cooperative Oncology Group performance status of ≤ 2 in module 1, or 0 or 1 in modules 2 and 3
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
4. 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;
5. 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
6. Participants must have received at least 3 prior lines of treatment in module 1. In modules 2 and 3, participants must meet the phase-specific requirements for the number of prior lines of therapy.
7. The above is a summary of key criteria, other inclusion criteria details may apply

Exclusion criteria 15

1. Amyloidosis, plasma cell leukemia, Waldenstrom Macroglobulinemia, Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin Syndrome, or Smoldering Multiple Myeloma (compliant with WHO criteria);
2. 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.
3. Participants exhibiting clinical signs of central nervous system involvement of MM;
4. Participants with known COPD, or previous history of ILD/pneumonitis
5. Participants with known moderate or severe persistent asthma within the past 5 years, or uncontrolled asthma of any classification;
6. Participants who have severe cardiovascular disease which is not adequately controlled.
7. Participants who have a history of immunodeficiency disease.
8. Participants with peripheral neuropathy ≥ Grade 2.
9. Primary refractory MM.
10. Participants who have previously received anti-GPRC5D or MMAE-containing treatment.
11. Participants with a history of prior malignancy other than MM within 3 years prior to first dose of study intervention. some exceptions apply
12. Participants with previous history of active John Cunningham virus infection resulting in PML
13. 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 monocloncal antibody therapy
14. Participants who have uncontrolled severe illness including but not limited to ongoing active infection requiring therapeutic antibiotics and/or other administration
15. The above is a summary of key criteria, other exclusion criteria details may apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Occurrence of dose-limiting toxicities (Phase Ia dose escalation only).
2. Incidence and severity of AEs and SAEs.
3. these are the core primary endpoints of the study, module specific endpoints are available within the CSP

Secondary endpoints 4

1. Preliminary efficacy of AZD0305 according to IMWG 2016 response criteria as assessed by investigator, including response endpoints ORR, CRR (module 2 only), DoR, MRD negative CR rate (Modules 2 and 3 only), PFS, and OS.
2. PK parameters of AZD0305 (total ADC), total antibody (conjugated and unconjugated) and MMAE, including but not limited to AUC, Cmax, tmax, clearance, and half-life, as data allow.
3. The number and percentage of participants who develop Anti-Drug Antibody (ADA).
4. These are the core secondary endpoints of the study, module specific endpoints are available within the CSP

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

3 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications