Study of AZD9150 and MEDI4736 (Durvalumab) in Japanese Adult Patients With Advanced Solid Malignancies

Study Overview
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Brief Summary
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This is a phase I, open-label study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of AZD9150 monotherapy and AZD9150 in combination with durvalumab in Japanese patients with advanced solid malignancies.

Official Title
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A Phase I, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD9150 Monotherapy and AZD9150 in Combination With Durvalumab in Japanese Patients With Advanced Solid Malignancies

Conditions
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Advanced Solid Malignancies

Intervention / Treatment
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* Drug: AZD9150, Durvalumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male and female patients must be at least 20 years of age. Has an Eastern Cooperative Oncology Group (ECOG) PS score of 0 or 1. Has measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm by computerised tomography (CT) scan, except lymph nodes which must have minimum short axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases). Adequate organ and marrow function Female subjects of childbearing potential and male subjects with partners of childbearing potential should ensure use of a highly effective method of birth control as defined in study protocol Key Exclusion Criteria: Spinal cord compression unless asymptomatic and not requiring steroids for at least 4 weeks before the start of study treatment. Patients must have completed any previous cancer-related treatments before enrolment. Has active or prior autoimmune disease within the past 2 years Has active or prior inflammatory bowel disease or primary immunodeficiency Undergone an organ transplant that requires use of immunosuppressive treatment Abnormalities in rhythm, conduction or morphology of resting 12-lead ECG Prior exposure to AZD9150 or any other anti PD (L)1 antibody.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C1:AZD9150, C2:AZD9150+Durvalumab<br>After confirmed safety with Cohort 1, Cohort 2 will open | Drug: AZD9150, Durvalumab<br>* After confirmed safety with Cohort 1, Cohort 2 will open. Patients allocated in each cohort will be evaluated for DLT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From obtaining the first informed consent until 28 days after the last dose (AZD9150). In patients with Durvalumab until 90 days after the last dose (Durvalumab). Expected to be for up to 12 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | Pharmacokinetics (PK) parameters will be derived using standard non-compartmental methods. | From obtaining the first informed consent until 28 days after the last dose (AZD9150). In patients with Durvalumab for 90 days for the last dose (Durvalumab). Expected to be for up to 12 months. | 
| Overall response rate | Defined as the proportion of subjects who achieve a response. | Assessed at every even numbered cycle with RECIST until disease progression. Expected to be for up to 12 months. | 
| Duration of Response | Defined as the interval from the first documentation of response to the earlier of the first documentation of definitive disease progression or death from any cause. | Assessed at every even numbered cycle with RECIST until disease progression. Expected to be for up to 12 months. | 
| Area under the plasma concentration-time curve (AUC) | PK parameters will be derived using standard non-compartmental methods. | From obtaining the first informed consent until 28 days after the last dose (AZD9150). In patients with Durvalumab for 90 days for the last dose (Durvalumab). Expected to be for up to 12 months. |