A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma
- Registration Number
- NCT05205161
- Lead Sponsor
- AstraZeneca
- Brief 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
- Detailed Description
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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A (Dose Escalation): DL4 AZD0466 Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Part A (Dose Escalation): Dose Level (DL)-1 AZD0466 Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Part A (Dose Escalation): DL2 AZD0466 Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Part A (Dose Escalation): DL3 AZD0466 Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Part B (Dose Expansion): Cohort B1 (R/R MCL) AZD0466 Participants with advanced R/R MCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Part A (Dose Escalation): DL1 AZD0466 Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Part B (Dose Expansion): Cohort B2 (R/R FL or MZL) AZD0466 Participants with advanced R/R FL or MZL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Part B (Dose Expansion): Cohort B3 (R/R DLBCL) AZD0466 Participants with advanced R/R DLBCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AE) Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month The safety and the tolerability of AZD0466 in patients with relapsed/ refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) was evaluated.
Number of Participants With Dose Limiting Toxicity (DLT) Day 1 to end of Cycle 1 (28 days treatment cycle) The DLT of AZD0466 in participants with R/R B-NHL was evaluated.
- Secondary Outcome Measures
Name Time Method Part A: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320 Cycle 1 Day 8, Cycle 2 Day 1 The Cmax of AZD4320 was assessed to characterise the pharmacokinetic (PK) profile of AZD0466.
Part A: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) of AZD4320 Cycle 1 Day 8, Cycle 2 Day 1 The tmax of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Part A: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) of AZD4320 Cycle 1 Day 8 (Study Day 8), Cycle 2 Day 1 (Study Day 22) The λz of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Part A: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) of AZD4320 Cycle 1 Day 8, Cycle 2 Day 1 The t1/2λz of AZD4320 was assessed to characterise Pk profile of AZD0466.
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After the Start of Infusion (AUC0-24) of AZD4320 Cycle 1 Day 8, Cycle 2 Day 1 The AUC0-24 of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (AUC0-72) of AZD4320 Cycle 1 Day 8 The AUC0-72 of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Part A: Area Under the Plasma Concentration-curve From Time 0 to the Last Quantifiable Concentration (AUClast) of AZD4320 Cycle 1 Day 8, Cycle 2 Day 1 The AUClast of AZD4320 was assessed to characterise the Pk profile of AZD0466
Part A: Time of Last Observed (Quantifiable) Concentration (Tlast) of AZD4320 Cycle 1 Day 8, Cycle 2 Day 1 The tlast of AZD4320 was assessed to characterise the Pk profile of AZD0466
Part A: Concentration Prior to Dosing (Ctrough) of AZD4320 Cycle 2 Day 1 The Ctrough of AZD4320 was assessed to characterise the Pk profile of AZD0466
Part A: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) of AZD4320 Cycle 1 Day 8, Cycle 2 Day 1 The Dose normalised AUClast of total AZD4320 was assessed to characterise the Pk profile of AZD0466
Part A: Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (Dose Normalised AUC0-72) of AZD4320 Cycle 1 Day 8 The Dose normalised AUC0-72 of total AZD4320 was assessed to characterise the Pk profile of AZD0466
Part A: Maximum Observed Plasma (Peak) Drug Concentration Divided by the Dose Administered (Dose Normalised Cmax) of AZD4320 Cycle 1 Day 8, Cycle 2 Day 1 The Dose normalised Cmax of total AZD4320 was assessed to characterise the Pk profile of AZD0466
Trial Locations
- Locations (1)
Research Site
🇪🇸Salamanca, Spain