This is a Phase 1, open-label study of ceralasertib given in combination with durvalumab in Chinese participants with advanced solid tumours. In each cohort, a monotherapy lead-in period (Cycle 0, duration of 7 or 14 days), prior to dosing with durvalumab, is added to investigate the PK profile and safety/tolerability of ceralasertib in Chinese participants. This study is designed to investigate and characterise preliminary safety, tolerability, and PK of ceralasertib in DLT-evaluable Chinese participants
\<Objectives\> Primary Objective: To assess the safety and tolerability of ceralasertib in combination with durvalumab in Chinese patients with advanced solid tumours refractory/resistant to prior SoC therapy or for which no appropriate SoC therapy exists. Secondary Objective: To characterise the PK profile of ceralasertib after single- and multiple-doses administration. To characterise the anti-tumour activity and efficacy of ceralasertib in combination with durvalumab in Chinese patients . \<Overall design\> This is a Phase 1, open-label study of ceralasertib given in combination with durvalumab in Chinese patients with advanced solid tumours.Results from this study will provide dose rationale for future investigations.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Ceralasertib (AZD6738) is a potent, selective inhibitor of the serine/threonine-specific protein kinase, ATR, with good selectivity against other phosphatidylinositol 3-kinase-related kinase family members.
Durvalumab is a human mAb of the immunoglobulin G 1 kappa subclass that blocks the interaction of PD-L1 (but not PD-L2) with PD-1 on T cells and CD80 (B7.1) on immune cells.
Research Site
Beijing, China
Research Site
Shandong, China
The number of subjects with dose-limiting toxicity, as defined in the protocol.
Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optional therapeutic intervention, meets protocol-defined criteria.
Time frame: From the first dose of study treatment Up to and including the end of cycle 1(each cycle is 28 days) .
Safety and tolerability in terms of adverse events
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Time frame: From the first dose of study treatment until 28 days after the last dose.
Plasma ceralasertib concentration(Cmax)
Observed PK parameters of ceralasertib
Time frame: Cycle 0 Day1 to Day7, Cycle1 Day1 and Cycle 1 Day 7 or Day 8. At the end of Cycle1(each cycle is 28 days)
Area under the plasma concentration versus time curve(AUC)
Observed PK parameters of ceralasertib.
Time frame: Cycle 0 Day1 to Day7, Cycle1 Day1 and Cycle1 Day7 or Day8. At the end of Cycle1(each cycle is 28 days)
Overall response rate
Antitumor activity by evaluation of tumor response assessments using RECIST 1.1
Time frame: At screening and Every 8 weeks ±1 week relative to the start of therapy (Cycle 1 Day 1, each cycle is 28days) until objective disease progression as defined by RECIST version 1.1
Duration of Response
Antitumor activity by evaluation of tumor response assessments using RECIST 1.1
Time frame: At screening and Every 8 weeks ±1 week relative to the start of therapy (Cycle 1 Day 1, each cycle is 28 days) until objective disease progression as defined by RECIST version 1.1
Percentage Change in Tumour Size
Antitumor activity by evaluation of tumor response assessments using RECIST 1.1
Time frame: At screening and Every 8 weeks ±1 week relative to the start of therapy (Cycle 1 Day 1, each cycle is 28 days) until objective disease progression as defined by RECIST version 1.1
Progression Free Survival
Antitumor activity by evaluation of tumor response assessments using RECIST 1.1
Time frame: From start of treatment until the date of objective disease progression or death. (approximately 6 months).
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