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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06106945
• Other study ID #: D7230C00001
• Secondary ID: 2023-508590-89-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 5, 2023
• Est. completion date: November 11, 2025

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: November 11, 2025
• Est. primary completion date: November 11, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• AZD0305
AZD0305

Locations

Country	Name	City	State
Australia	Research Site	Melbourne
Australia	Research Site	Perth
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
China	Research Site	Beijing
France	Research Site	Lille
France	Research Site	Nantes
Germany	Research Site	Freiburg
Germany	Research Site	Hamburg
Germany	Research Site	Lübeck
Germany	Research Site	Nürnberg
Germany	Research Site	Wuerzburg
Japan	Research Site	Kashiwa
Japan	Research Site	Nagoya-shi
Japan	Research Site	Yamagata-shi
Spain	Research Site	Madrid
Spain	Research Site	Pamplona
Spain	Research Site	Salamanca
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Atlanta	Georgia
United States	Research Site	Duarte	California
United States	Research Site	Fairfax	Virginia
United States	Research Site	Irvine	California
United States	Research Site	New York	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  France,  Germany,  Japan,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of dose-limiting toxicity (DLT), as defined in the protocol (Phase Ia dose escalation only)	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	From first dose of study treatment until the end of Cycle 1
Primary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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 to progressive disease or Initiation of subsequent MM therapy (approximately 2 years)
Secondary	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 to confirmed progressive disease or death (approximately 2 years)
Secondary	Phase Ib: Progression free Survival (PFS)	The time from randomization until IMWG defined disease progression or death	From randomization to progressive disease or death in the absence of disease progression (approximately 2 years)
Secondary	Phase Ib: Overall Survival (OS)	The time from randomization until death due to any cause	From randomization to death (approximately 2 years)
Secondary	Phase Ib: Pharmacokinetics of AZD0305: Area Under the concentration-time curve (AUC)	Area under the plasma concentration-time curve	From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Secondary	Phase Ib: Pharmacokinetics of AZD0305: Maximum plasma concentration of the study drug (Cmax)	Maximum observed plasma concentration of the study drug	From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Secondary	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, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Secondary	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, at predefined intervals throughout the administration of AZD0305 (approximately 2 years
Secondary	Phase Ib: Pharmacokinetics of AZD0305: Terminal elimination half-life (t 1/2)	Terminal elimination half-life	From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Secondary	Phase Ib: Immunogenicity of AZD0305	The number and percentage of participants who develop ADAs	From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)