Clinical trial NCT06106945: AZD0305 as Monotherapy or in Combination With Anticancer Agents in Participants With Relapsed/Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: GPRC5D
ADC
AZD0305
Relapsed Refractory Multiple Myeloma
RRMM
MMAE
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-10-30
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: This protocol has a modular design, with the potential for future treatment arms, study parts, or modules to be added via protocol amendments. Module 1 will include Phase Ia (Dose escalation), and Phase Ib (Dose expansion/optimization).
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of dose-limiting toxicity (DLT), as defined in the protocol (Phase Ia dose escalation only)
timeFrame: From first dose of study treatment until the end of Cycle 1
measure: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From time of Informed consent to 30 days post end of treatment
Secondary outcomes:
measure: Phase Ia: Objective Response Rate (ORR)
timeFrame: From first dose of AZD0305 to progressive disease or Initiation of subsequent MM therapy (approximately 2 years)
measure: Phase Ia: Duration of response (DoR)
timeFrame: From the first documented response to confirmed progressive disease or death (approximately 2 years)
measure: Phase Ia: Progression free Survival (PFS)
timeFrame: From first dose of AZD0305 to progressive disease or death in the absence of disease progression (approximately 2 years)
measure: Phase Ia: Overall Survival (OS)
timeFrame: From first dose of AZD0305 to death (approximately 2 years)
measure: Phase Ia: Pharmacokinetics of AZD0305: Area Under the concentration-time curve (AUC)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ia: Pharmacokinetics of AZD0305: Maximum plasma concentration of the study drug (Cmax)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ia: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (tmax)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ia: Pharmacokinetics of AZD0305: Clearance
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ia: Pharmacokinetics of AZD0305: Terminal elimination half-life (t 1/2)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ia: Immunogenicity of AZD0305
timeFrame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ib: Objective Response Rate (ORR)
timeFrame: From randomization to progressive disease or Initiation of subsequent MM therapy (approximately 2 years)
measure: Phase Ib: Duration of response (DoR)
timeFrame: From randomization to confirmed progressive disease or death (approximately 2 years)
measure: Phase Ib: Progression free Survival (PFS)
timeFrame: From randomization to progressive disease or death in the absence of disease progression (approximately 2 years)
measure: Phase Ib: Overall Survival (OS)
timeFrame: From randomization to death (approximately 2 years)
measure: Phase Ib: Pharmacokinetics of AZD0305: Area Under the concentration-time curve (AUC)
timeFrame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ib: Pharmacokinetics of AZD0305: Maximum plasma concentration of the study drug (Cmax)
timeFrame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ib: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (tmax)
timeFrame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ib: Pharmacokinetics of AZD0305: Clearance
timeFrame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years
measure: Phase Ib: Pharmacokinetics of AZD0305: Terminal elimination half-life (t 1/2)
timeFrame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
measure: Phase Ib: Immunogenicity of AZD0305
timeFrame: From randomization, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Irvine
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Melbourne
country: Australia
facility: Research Site
city: Nedlands
country: Australia
facility: Research Site
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Nürnberg
country: Germany
facility: Research Site
city: Wuerzburg
country: Germany
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Yamagata-shi
country: Japan
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
Study officials:
References: