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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: AZD0305


Participation Criteria
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Eligibility Criteria
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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: 1) 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. 5. 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). 4. 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. 5. Subject is exhibiting clinical signs of central nervous system (CNS) involvement of MM. 6. Subject with known chronic obstructive pulmonary disease (COPD). 7. Subjects who have severe cardiovascular disease,

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Phase I (Dose escalation) followed by the Phase II (Dose expansion)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD0305 monotherapy<br>Phase1: AZD0305 will be prescribed at specified dose levels. Phase 2: AZD0305 will be prescribed as RP2D. | Drug: AZD0305<br>* AZD0305<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Number of patients with dose-limiting toxicity (DLT), as defined in the protocol. | 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. | From first dose of study treatment until the end of Cycle 1 (approximately 21 days). | 
| Phase I: Number of patients with adverse events (AEs) | Number of patients with adverse events by system organ class and preferred term | From time of Informed consent to 30 days post last dose (approximately 14 months). | 
| Phase I: Number of patients with serious adverse events (SAEs) | Number of patients with serious adverse events by system organ class and preferred term | From time of Informed consent to 30 days post last dose (approximately 14 months). | 
| Phase II: 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: 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 14 months) | 
| Phase I: 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 14 months) | 
| Phase I: 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 14 months) | 
| Phase I: 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 14 months) | 
| Phase I: 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 14 months) | 
| Phase I: 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 14 months) | 
| Phase I: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (T-max) | 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 14 months) | 
| Phase I: 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 14 months) | 
| Phase I: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 14 months) | 
| Phase I: 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 14 months) | 
| Phase II: 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) | 
| Phase II: 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) | 
| Phase II: 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) | 
| Phase II: 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) | 
| Phase II: 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) | 
| Phase II: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (T-max) | 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) | 
| Phase II: 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) | 
| Phase II: Minimal Residual Disease (MRD) | MRD assessment in subjects who achieved CR or better | From first dose of AZD0305 to progressive disease or Initiation of subsequent MM therapy (approximately 2 years) | 
| Phase II: Adverse Events (AEs), | Number of patients with adverse events by system organ class and preferred term | From time of Informed consent to 30 days post last dose (approximately 2 years) | 
| Phase II Serious Adverse Events (SAEs) | Number of patients with serious adverse events by system organ class and preferred term | From time of Informed consent to 30 days post last dose (approximately 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADC, GPRC5D, AZD0305, Relapsed Refractory Multiple Myeloma, RRMM, MMAE