AZD0305 as Monotherapy or in Combination With Anticancer Agents in Participants With Relapsed/Refractory Multiple Myeloma
PHASE1PHASE2RECRUITING
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.
Study details:
This study will follow a modular protocol design evaluating AZD0305 as monotherapy and in combination with other anticancer agents. The protocol may be amended in the future to incorporate further monotherapy expansion at the recommended Phase 2 dose (RP2D) in Phase II, and/or additional modules investigating AZD0305 in combination with other anticancer agents. The study consists of 3 modules:.
* Module 1 (AZD0305 monotherapy),. * Module 2 (AZD0305 in combination with elranatamab). * Module 3 (AZD0305 in combination with pomalidomide and dexamethasone \[Pd\]).
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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).
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.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1PHASE2
Study ID
NCT06106945
Intervention or treatment
DRUG: AZD0305
Conditions
- Multiple Myeloma
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Research sites nearby
Closest Location:
Research Site
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Research Site
Melbourne, Australia
Research Site
Nedlands, Australia
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Who is running the clinical trial?
A
AstraZeneca
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: AZD0305 monotherapy
| Drug: AZD0305 |
EXPERIMENTAL: AZD0305 + Elranatamab
| Drug: AZD0305, Drug: Elranatamab |
EXPERIMENTAL: AZD0305 + Pomalidomide and Dexamethasone
| Drug: AZD0305, Drug: Pomalidomide, Drug: Dexamethasone |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| Phase Ib: Overall Survival (OS) | The time from randomization until death due to any cause | From randomization to death (approximately 2 years) |
| 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) |
| 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) |
| 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) |
| 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 |
| 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) |
| 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) |
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References
Clinical Trials Gov: AZD0305 as Monotherapy or in Combination With Anticancer Agents in Participants With Relapsed/Refractory Multiple MyelomaOther trials to consider
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