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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Malignancies
• Intervention / Treatment: Drug: AZD9150, Durvalumab

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kashiwa, Japan, 277-8577
    • Research Site
  • Matsuyama-shi, Japan, 791-0280
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Nishina T, Fujita T, Yoshizuka N, Sugibayashi K, Murayama K, Kuboki Y. Safety, tolerability, pharmacokinetics and preliminary antitumour activity of an antisense oligonucleotide targeting STAT3 (danvatirsen) as monotherapy and in combination with durvalumab in Japanese patients with advanced solid malignancies: a phase 1 study. BMJ Open. 2022 Oct 21;12(10):e055718. doi: 10.1136/bmjopen-2021-055718.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2018
• Primary Completion (Actual): April 12, 2019
• Study Completion (Actual): April 12, 2019

Study Registration Dates

• First Submitted: November 10, 2017
• First Submitted That Met QC Criteria: January 3, 2018
• First Posted (Actual): January 9, 2018

Study Record Updates

• Last Update Posted (Actual): June 24, 2019
• Last Update Submitted That Met QC Criteria: June 21, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: D5660C00017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No