AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Blood Cancer.

Titre officiel

A Modular Phase I/II, Open-label, Multicentre Study to Assess AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Haematological Malignancies

Sommaire:

This is a modular, multicentre, open-label, non-randomised, Phase I/II, dose-setting and expansion study including an intra-participant ramp-up. AZD4573 will be administered intravenously, in novel combinations with anti-cancer agents, to participants with relapsed/refractory haematological malignancies.

Description de l'essai

Primary Outcome:

• Module 1 Part A : Number of participants with serious and non-serious adverse events
• Module 1 Part B: Overall response rate (ORR) of AZD4573 in combination with acalabrutinib

Secondary Outcome:

• Module 1 Part B: Efficacy of AZD4573 in combination with acalabrutinib by evaluation of tumour response and overall survival via CR rate
• Module 1 Part B: Efficacy of AZD4573 in combination with acalabrutinib by evaluation of tumour response and overall survival via duration of response (DoR)
• Module 1 Part B: Efficacy of AZD4573 in combination with acalabrutinib by evaluation of tumour response and overall survival via Time to Response (TTR)
• Module 1 Part B: Efficacy of AZD4573 in combination with acalabrutinib by evaluation of tumour response and overall survival via Progression free survival (PFS)
• Module 1 Part B: Efficacy of AZD4573 in combination with acalabrutinib by evaluation of tumour response and overall survival via Overall survival (OS)
• Module 1 Part B: Number of participants with serious and non-serious adverse events
• Module 1 Part A and Part B: Plasma pharmacokinetics (PK) (Cmax) of AZD4573 and acalabrutinib (plus its active metabolite ACP-5862), when given in combination
• Module 1 Part A and Part B: Plasma PK (AUC0-t) of AZD4573 and acalabrutinib (plus its active metabolite ACP-5862), when given in combination
• Module 1 Part A and Part B: Plasma PK (AUClast) of AZD4573 and acalabrutinib (plus its active metabolite ACP-5862), when given in combination
• Module 1 Part A and Part B: Plasma PK (AUCinf) of AZD4573 and acalabrutinib (plus its active metabolite ACP-5862), when given in combination
• Module 1 Part A and Part B: Plasma PK (tmax) of AZD4573 and acalabrutinib (plus its active metabolite ACP-5862), when given in combination
• Module 1 Part A and Part B: Plasma PK (t1/2) of AZD4573 and acalabrutinib (plus its active metabolite ACP-5862), when given in combination

In Module 1 Part A (dose-setting), this study module will initially explore once weekly administration of AZD4573 at up to three target dose levels in combination with oral acalabrutinib 100 mg twice daily and will enroll participants with Diffuse large B-cell lymphoma (DLBCL), based on the observation of complete and partial responses amongst DLBCL patients treated with monotherapy. The primary objective of Part A will be to identify the maximum tolerated dose and/or Recommended Phase II dose (RP2D) for further evaluation in Part B. In Module 1 Part B (expansion), separate expansion cohorts for participants with Germinal Centre B-cell (GCB) and non-GCB DLBCL subtypes will be opened at the RP2D.

Voir cet essai sur ClinicalTrials.gov