A Study to Evaluate Safety, PK, PD and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With R/R B-Cell Malignancies.
NCT Number: NCT06542250
Acronym: TITANium
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: B-cell Malignancies
Interventions: DRUG: AZD5492
Sponsor: AstraZeneca
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 174
Study Design: Allocation: NA|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-29
Completion Date: 2028-02-17
Locations: Research Site, La Jolla, California, 92093, United States|Research Site, Boston, Massachusetts, 02215, United States|Research Site, Hackensack, New Jersey, 07601, United States|Research Site, New York, New York, 10029, United States|Research Site, Charlotte, North Carolina, 28204, United States|Research Site, Houston, Texas, 77030, United States|Research Site, Seattle, Washington, 98109, United States|Research Site, Melbourne, 3000, Australia|Research Site, Calgary, Alberta, T2N 4N2, Canada|Research Site, Toronto, Ontario, M5G 2M9, Canada|Research Site, Montreal, Quebec, H3T 1R2, Canada|Research Site, Pessac, 33604, France|Research Site, München, 81675, Germany|Research Site, Ulm, 89081, Germany|Research Site, Bologna, 40138, Italy|Research Site, Milano, 20133, Italy|Research Site, Barcelona, 08035, Spain|Research Site, L'Hospitalet de Llobregat, 08908, Spain|Research Site, Madrid, 28040, Spain

Summary:
This is a Phase I/II study designed to evaluate if experimental T cell engaging antibody targeting CD20 AZD5492 is safe, tolerable and efficacious in participants with Relapsed or Refractory B-Cell Malignancies.

Primary Outcome Measures: Frequency of dose limiting toxicities (DLTs)., DLTs are dose-limiting toxicities as defined in the study protocol., Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).|Safety evaluation of AZD5492: Number of participants with treatment-related adverse events., Incidence and severity of AEs, AESIs, and SAEs, Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.|Tolerability evaluation of AZD5492: Number of participants with treatment-related adverse events., SAEs/AEs leading to discontinuation of AZD5492., Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
Secondary Outcome Measures: Overall Response Rate (ORR), The proportion of participants with a complete response or partial response, according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL., Module 1 - From first dose of AZD5492 up to approximately 2 years.|Complete Response Rate (CR Rate), The proportion of participants with a complete response (CR), according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL., Module 1 - From first dose of AZD5492 up to approximately 2 years.|Duration of Response (DoR), The time from the date of first documented response until the date of documented progression (according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL) or death due to any cause., Module 1 - From first dose of AZD5492 up to approximately 2 years.|Progression-free Survival (PFS), The time from the date of first dose until the date of documented disease progression (according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL) or death due to any cause., Module 1 - From first dose of AZD5492 up to approximately 2 years.|Overall Survival (OS), The time from the date of first dose until date of death due to any cause., Module 1 - From first dose of AZD5492 up to approximately 2 years.|Pharmacokinetics of AZD5492: serum concentration of study drug, Maximum observed serum concentration of AZD5492., Module 1 - From informed consent until 90 days after last dose of AZD5492.|Pharmacokinetics of AZD5492: Maximum plasma concentration of the study drug (Cmax)., Maximum observed plasma concentration of AZD5492., Module 1 - From informed consent until 90 days after last dose of AZD5492.|Pharmacokinetics of AZD5492: Area under the concentration time curve (AUC)., Area under the plasma concentration-time curve., Module 1 - From informed consent until 90 days after last dose of AZD5492.|Pharmacokinetics of AZD5492: apparent clearance, The volume of plasma from which the study drug is completely removed per unit time., Module 1 - From informed consent until 90 days after last dose of AZD5492.|Pharmacokinetics of AZD5492: Half-life (t 1/2), Terminal elimination half-life., Module 1 - From informed consent until 90 days after last dose of AZD5492.|To determine the immunogenicity of AZD5492, The number of participants who develop ADAs measured in serum., Module 1 - From informed consent until 90 days after last dose of AZD5492.|To determine the immunogenicity of AZD5492, The percentage of participants who develop ADAs measured in serum., Module 1 - From informed consent until 90 days after last dose of AZD5492.