A Phase I/II Study of AZD0305 for Relapsed/Refractory Multiple Myeloma

Sponsor

AstraZeneca (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06106945

Collaborator

(none)

Enrollment

Arm

23.2

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a Phase I/II, Open-Label, Multiple Centre Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of AZD0305 in Patients with Relapsed or Refractory Multiple Myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: AZD0305	Phase 1/Phase 2

Detailed Description

This is a phase I/II, open-label, dose escalation and expansion study to evaluate the safety and tolerability, PK, immunogenicity and preliminary efficacy of AZD0305 in patients subjects with relapsed or refractory multiple myeloma (RRMM). The study includes a dose escalation and a dose expansion.

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

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Phase I (Dose escalation) followed by the Phase II (Dose expansion)Phase I (Dose escalation) followed by the Phase II (Dose expansion)

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II, Open-Label, Multiple Centre Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of AZD0305 in Patients With Relapsed or Refractory Multiple Myeloma

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Nov 7, 2025

Anticipated Study Completion Date :

Nov 7, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD0305 monotherapy Phase1: AZD0305 will be prescribed at specified dose levels. Phase 2: AZD0305 will be prescribed as RP2D.	Drug: AZD0305 AZD0305

Arm

Intervention/Treatment

Experimental: AZD0305 monotherapy

Phase1: AZD0305 will be prescribed at specified dose levels. Phase 2: AZD0305 will be prescribed as RP2D.

Drug: AZD0305

AZD0305

Outcome Measures

Primary Outcome Measures

Phase I: Number of patients with dose-limiting toxicity (DLT), as defined in the protocol. [From first dose of study treatment until the end of Cycle 1 (approximately 21 days).]
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 pre-defined haematological and non-haematological toxicities.
Phase I: Number of patients with adverse events (AEs) [From time of Informed consent to 30 days post last dose (approximately 14 months).]
Number of patients with adverse events by system organ class and preferred term
Phase I: Number of patients with serious adverse events (SAEs) [From time of Informed consent to 30 days post last dose (approximately 14 months).]
Number of patients with serious adverse events by system organ class and preferred term
Phase II: Objective Response Rate (ORR) [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

Secondary Outcome Measures

Phase I: Objective Response Rate (ORR) [From first dose of AZD0305 to progressive disease or Initiation of subsequent MM therapy (approximately 14 months)]
The percentage of patients with a confirmed investigator assessed sCR, CR, VGPR or PR according to IMWG criteria
Phase I: Duration of response (DoR) [From the first documented response to confirmed progressive disease or death (approximately 14 months)]
The time from the date of first response until date of disease progression or death in the absence of disease progression
Phase I: Progression free Survival (PFS) [From first dose of AZD0305 to progressive disease or death in the absence of disease progression (approximately 14 months)]
The time from first dose until IMWG defined disease progression or death
Phase I: Overall Survival (OS) [From first dose of AZD0305 to death (approximately 14 months)]
The time from the date of the first dose of study treatment until death due to any cause.
Phase I: 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 14 months)]
Area under the plasma concentration-time curve
Phase I: Pharmacokinetics of AZD0305: Maximum plasma concentration of the study drug (Cmax) [From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 14 months)]
Maximum observed plasma concentration of the study drug
Phase I: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (T-max) [From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 14 months)]
Time to maximum observed plasma concentration of the study drug
Phase I: Pharmacokinetics of AZD0305: Clearance [From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 14 months)]
A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.
Phase I:Pharmacokinetics of AZD0305: Terminal elimination half-life (t 1/2) [From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 14 months)]
Terminal elimination half life.
Phase I: Immunogenicity of AZD0305 [From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 14 months)]
The number and percentage of participants who develop ADAs.
Phase II: Duration of response (DoR) [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
Phase II: Progression free Survival (PFS) [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
Phase II: Overall Survival (OS) [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.
Phase II: 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)]
Area under the plasma concentration-time curve
Phase II: Pharmacokinetics of AZD0305: Maximum plasma concentration of the study drug (Cmax) [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
Phase II: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (T-max) [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
Phase II: Immunogenicity of AZD0305 [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.
Phase II: Minimal Residual Disease (MRD) [From first dose of AZD0305 to progressive disease or Initiation of subsequent MM therapy (approximately 2 years)]
MRD assessment in subjects who achieved CR or better
Phase II: Adverse Events (AEs), [From time of Informed consent to 30 days post last dose (approximately 2 years)]
Number of patients with adverse events by system organ class and preferred term
Phase II Serious Adverse Events (SAEs) [From time of Informed consent to 30 days post last dose (approximately 2 years)]
Number of patients with serious adverse events by system organ class and preferred term

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Life expectancy ≥ 6 months.
Subject must have receive 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).
Subject must have one or more measurable disease as the following measurements:

Serum M protein level ≥0.5g/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.

Subjects must show appropriate organ and marrow function.

Key Exclusion Criteria:

Subject has received anti-GPRC5D treatment previously.
Subject has previously received allogenic stem cell transplant, or subject has received autologous stem cell transplant within 3 months before administration of the IMP.
Primary refractory multiple myeloma (subject failed to generate any minimal response or any degree of response to any therapy).
Subject has received anti myeloma treatment (radiotherapy is excluded) within 2 weeks or 5 PK half-lives of the treatment, whichever longer, before the first study agent administration.
Subject is exhibiting clinical signs of central nervous system (CNS) involvement of MM.
Subject with known chronic obstructive pulmonary disease (COPD). 7. Subjects who have severe cardiovascular disease,