A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma

Official Title

A Modular Phase I/II, Open-label, Dose Escalation and Expansion, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Patients With Advanced Non-Hodgkin Lymphoma

Summary:

This study evaluates the safety, tolerability, PK, and preliminary efficacy of AZD0466 as monotherapy or in combination with other anticancer agents in patients with advanced NHL

Trial Description

Primary Outcome:

  • Part A: Incidence of adverse events (AEs) and dose-limiting toxicities (DLTs)
  • Part B: Objective Response Rate (ORR)
Secondary Outcome:
  • Part B: Incidence of adverse events (AEs) and serious adverse events (SAEs)
  • Part B: Complete Response (CR) Rate
  • Part B: Duration of Response (DoR)
  • Part B: Time to Response (TTR)
  • Part B: Progression-free Survival (PFS)
  • Part B: Overall Survival (OS)
  • Part A and Part B: Maximum observed plasma (peak) drug concentration (Cmax)
  • Part A and Part B: Time to reach peak or maximum observed concentration or response following drug administration (tmax)
  • Part A and Part B: Terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz)
  • Part A and Part B: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz)
  • Part A and Part B: Partial area under the plasma concentration-time curve from time 0 to 24 hours after the start of infusion (AUC0-24)
  • Part A and Part B: Partial area under the plasma concentration-time curve from time 0 to 72 hours after the start of infusion (AUC0-72)
  • Part A and Part B: Area under the plasma concentration-curve from time 0 to the last quantifiable concentration (AUClast)
  • Part A and Part B: Time of last observed (quantifiable) concentration (tlast)
  • Part A and Part B: Concentration prior to dosing (Ctrough)
  • Part A and Part B (total AZD4320 only): Area under the plasma concentration-time curve from time 0 to time of last quantifiable analyte concentration divided by the dose administered (Dose normalised AUClast)
  • Part A and Part B (total AZD4320 only): Area under the plasma concentration-time curve from time 0 to 72 hours after the start of infusion (Dose normalised AUC0-72)
  • Part A and Part B (total AZD4320 only): Maximum observed plasma (peak) drug concentration divided by the dose administered (Dose normalised Cmax)

This is a modular Phase I/II, open-label, dose escalation and expansion, multicentre Study. The study consists of individual modules, each evaluating the safety and tolerability of AZD0466 as monotherapy or with a specific combination treatment. The initial components are the core protocol, which contains information applicable to all modules, and Module 1.

Module 1 will evaluate the safety, tolerability, PK, and preliminary efficacy of AZD0466 monotherapy and will include 2 parts. Part A dose escalation and Part B dose expansion cohorts. Part A will enrol patients with advanced B-NHL and once the RP2D has been determined, Part B may open to further explore the preliminary anticancer efficacy of AZD0466 monotherapy in patients with selected lymphoid malignancies.

Part A: Phase 1 dose setting to assess the safety and tolerability and determine dose(s) and schedule(s) to be evaluated in Part B.

Part B: Phase 1b/2a dose expansion to assess the efficacy of AZD0466 in 3 select patient populations: relapsed/refractory (R/R) mantle cell lymphoma (MCL) (Cohort B1), R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) (Cohort B2), and R/R diffuse large B-cell lymphoma (DLBCL) (Cohort B3).

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society