This is a modular dose confirmation and expansion study. The core study design is to assess the efficacy of AZD4573, administered as monotherapy or combination therapy, to participants with either r/r PTCL or r/r cHL and to confirm the safety profiles and PK in these populations. Module 1 of this study will evaluate the efficacy, safety, and tolerability of AZD4573 monotherapy in participants with r/r PTCL or r/r cHL. If AZD4573 monotherapy is found to have promising anti-tumour efficacy in Module 1, an AZD4573 monotherapy Phase II expansion may be added via a substantial protocol amendment.
Module 1 will consist of two r/r PTCL cohorts and one cHL cohort; and each cohort includes 21 participants. A comprehensive initial review of all safety and PK/PD data will be conducted in approximately the first 6 participants of each cohort (safety run-in), with separate Safety Review Committees (SRCs) for each cohort executed independently. The safety assessment will be undertaken by the SRC. Each cohort will have a separate dose confirmation, assessed independently by the SRC, to assess safety and PK/PD data compared to the known profiles in the first time in human study (Study D8230C00001) lymphoma population. These SRC reviews will confirm whether the recommended phase II dose for lymphoma (IV infusion 12 mg once weekly, including intra-participant ramp-up) is safe and tolerable or if additional dose optimisation is indicated at a revised dose and/or schedule. All cohorts can be opened and delivered independently of each other.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
52
AZD4573 will be given intravenously
Research Site
Duarte, California, United States
Research Site
Boston, Massachusetts, United States
Research Site
Hackensack, New Jersey, United States
Research Site
Houston, Texas, United States
Research Site
Salt Lake City, Utah, United States
Research Site
Seattle, Washington, United States
Research Site
Clayton, Australia
Research Site
Melbourne, Australia
Research Site
Nedlands, Australia
Research Site
Besançon, France
...and 17 more locations
Objective Response Rate (ORR)
Objective response rate is defined as the proportion of participants who have a tumour response of complete response \[CR\] or partial response \[PR\] according to the Lugano (2014) response criteria for malignant lymphoma.
Time frame: From Screening (Day -30 to Day-1) until disease progression or survival until death (26 months)
Complete Response (CR) Rate
Complete response rate is defined as proportion of participants who have a complete response according to the Lugano (2014) response criteria.
Time frame: From Screening (Day -30 to Day-1) until disease progression or survival until death (26 months).
Duration of Response (DoR)
Duration of response is defined as the time from the first objective response to the time of documented disease progression or death due to any cause, whichever occurs first.
Time frame: From Screening (Day -30 to Day-1) until disease progression or survival until death (26 months).
Progression-free Survival (PFS)
Progression-free survival is defined as the time from the date of first dose to documented disease progression, or death from any cause, whichever occurs first.
Time frame: From Screening (Day -30 to Day-1) until disease progression or survival until death (26 months).
Overall Survival (OS)
Overall survival is defined as the time from the date of first dose to death from any cause.
Time frame: From Screening (Day -30 to Day-1) until disease progression or survival until death (26 months).
Number of Participants With Adverse Events (AE) and Serious AEs (SAE)
The safety and tolerability of AZD4573 was assessed.
Time frame: From treatment period (Cycle 1) to follow up visit (30 [± 7] ) days from the last dose (upto 26 months).
Maximum Observed Plasma (Peak) Drug Concentration (Cmax)
The plasma PK of AZD4573 when administered in participants was assessed.
Time frame: Cycle 1 (Cycle length is 35 days), Day 1 of Weeks 1-3 and Cycle 2 (Cycle length is 21 Days), Day 1.
Area Under the Plasma Concentration Curve From Zero to the Last Quantifiable Concentration (AUClast)
The plasma PK of AZD4573 when administered in participants was assessed.
Time frame: Cycle 1 (Cycle length is 35 days), Day 1 of Weeks 1-3 and Cycle 2 (Cycle length is 21 Days), Day 1.
Area Under Plasma Concentration Time Curve From Zero to Infinity (AUC0-inf) of AZD4573
The plasma PK of AZD4573 when administered in participants was assessed.
Time frame: Cycle 1 (Cycle length is 35 days), Day 1 of Weeks 1-3 and Cycle 2 (Cycle length is 21 Days), Day 1.
Time to Reach Peak Observed Concentration Following Drug Administration (Tmax)
The plasma PK of AZD4573 when administered in participants was assessed.
Time frame: Cycle 1 (Cycle length is 35 days), Day 1 of Weeks 1-3 and Cycle 2 (Cycle length is 21 Days), Day 1.
Half-life (t1/2) of AZD4573
The plasma PK of AZD4573 when administered in participants was assessed.
Time frame: Cycle 1 (Cycle length is 35 days), Day 1 of Weeks 1-3 and Cycle 2 (Cycle length is 21 Days), Day 1.
Systematic Clearance (CL)
The plasma PK of AZD4573 when administered in participants was assessed.
Time frame: Cycle 1 (Cycle length is 35 days), Day 1 of Weeks 1-3 and Cycle 2 (Cycle length is 21 Days), Day 1.
Volume of Distribution at Terminal Phase (Vz)
The plasma PK of AZD4573 when administered in participants was assessed.
Time frame: Cycle 1 (Cycle length is 35 days), Day 1 of Weeks 1-3 and Cycle 2 (Cycle length is 21 Days), Day 1.
Volume of Distribution at Steady State (Vss)
The plasma PK of AZD4573 when administered in participants was assessed.
Time frame: Cycle 1 (Cycle length is 35 days), Day 1 of Weeks 1-3 and Cycle 2 (Cycle length is 21 Days), Day 1.
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