AZD3470 as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Haematologic Malignancies.
Start Date
1/23/2024
Completion Date
5/3/2029
Summary
This study is designed to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy following oral administration of AZD3470 as a monotherapy, and in combination with other anticancer agents in participants with haematologic malignancies.
Detailed Description
This is a modular, Phase I/II, open-label, multicentre study of AZD3470 in participants with haematologic malignancies. The study consists of several study modules, each evaluating the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of orally administered AZD3470 as a monotherapy and in combination with other anticancer agent(s). Module 1 Cohort 1 will evaluate AZD3470 monotherapy in adults and adolescents with r/r cHL who have received at least 2 prior lines of anticancer therapy. Part A (dose escalation) will assess AZD3470 at increasing doses to determine Maximum Tolerated Dose and Recommended Dose for Expansion in participants aged 18 years or older. Part B (dose optimization/expansion) will include participants to selected dose levels that were evaluated in Part A to support the recommended phase II dose (RP2D). Safety, tolerability, PK, preliminary efficacy, and food effect will be assessed. Adolescent participants (aged 12 years and older) will only be enrolled in Part B once sufficient supportive adult safety/PK data is reviewed and agreed upon with Safety Review Committee. Module 1 Cohort 2 will evaluate AZD3470 monotherapy as a consolidation therapy in advanced stage (Stage III/IV) cHL participants aged 50 years or older, who have achieved a response (CR or PR) after at least 4 cycles of frontline standard of care therapy. Safety and tolerability, PK, Pharmacodynamics and preliminary efficacy will be evaluated. Module 1 Cohort 3 will evaluate AZD3470 monotherapy in participants with r/r PTCL (PTCL NOS, ALCL, AITL) aged 18 years or older, who have received at least one prior anticancer therapy. Safety and tolerability, PK, Pharmacodynamics, and preliminary efficacy will be evaluated. Module 2 Cohort 1 will evaluate AZD3470 in combination with pembrolizumab in r/r cHL participants aged 18 years or older, who have received at least one prior anticancer therapy. Part A (dose escalation) will include participants at select dose levels below or at the highest tolerable monotherapy dose in Module 1 Cohort 1. Part B (dose optimization/expansion) will include participants to selected dose levels that were evaluated in Part A to support the recommended combination phase II dose (RP2D). Safety, tolerability, PK, Pharmacodynamics and preliminary efficacy, will be evaluated. The protocol may be amended in the future to incorporate additional cohorts in combination with pembrolizumab or new modules evaluating AZD3470 in combination with other anticancer agents in haematologic malignancies.
Eligibility Criteria
Age Range: 12 years to No maximum
Interventions
AZD3470
Pembrolizumab
Conditions
Locations
Research Site
Duarte, California 91010
United States
Research Site
Miami, Florida 33136
United States
Research Site
Atlanta, Georgia 30322
United States
Research Site
Boston, Massachusetts 02215
United States
Research Site
Boston, Massachusetts 02215
United States
Research Site
New York, New York 10016
United States
Research Site
Philadelphia, Pennsylvania 19104
United States
Research Site
Houston, Texas 77030
United States
Research Site
Adelaide, 5000
Australia
Research Site
Birtinya, 4575
Australia
Research Site
Fitzroy, 3065
Australia
Research Site
Nedlands, 6009
Australia
Research Site
South Brisbane, 4101
Australia
Research Site
Waratah, 2298
Australia
Research Site
Beijing, 100191
China
Research Site
Guangzhou, 510060
China
Research Site
Shanghai, 20032
China
Research Site
Créteil, 94010
France
Research Site
Dijon, 21079
France
Research Site
Lille, 59000
France
Research Site
Pierre-Bénite, 69310
France
Research Site
Villejuif, 94805
France
Research Site
Berlin, 12203
Germany
Research Site
Cologne, 50937
Germany
Research Site
Erlangen, 91054
Germany
Research Site
Würzburg, 97080
Germany
Research Site
Alessandria, 15100
Italy
Research Site
Bologna, 40138
Italy
Research Site
Milan, 20141
Italy
Research Site
Bunkyō City, 113-8677
Japan
Research Site
Kōtoku, 135-8550
Japan
Research Site
Seoul, 03080
South Korea
Research Site
Seoul, 06351
South Korea
Research Site
L'Hospitalet de Llobregat, 08908
Spain
Research Site
Madrid, 28041
Spain
Research Site
Manchester, M20 4BX
United Kingdom
Research Site
Oxford, OX3 7LE
United Kingdom