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

• ClinicalTrials.gov Identifier: NCT03394144
• Recruitment Status: Completed
• First Posted: January 9, 2018
• Last Update Posted: June 24, 2019
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Malignancies	Drug: AZD9150, Durvalumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 30, 2018
• Actual Primary Completion Date: April 12, 2019
• Actual Study Completion Date: April 12, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability in terms of adverse events [ Time Frame: 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. ]
   Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters

Secondary Outcome Measures :

1. Maximum plasma concentration (Cmax) [ Time Frame: 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. ]
   Pharmacokinetics (PK) parameters will be derived using standard non-compartmental methods.
2. Overall response rate [ Time Frame: Assessed at every even numbered cycle with RECIST until disease progression. Expected to be for up to 12 months. ]
   Defined as the proportion of subjects who achieve a response.
3. Duration of Response [ Time Frame: Assessed at every even numbered cycle with RECIST until disease progression. Expected to be for up to 12 months. ]
   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.
4. Area under the plasma concentration-time curve (AUC) [ Time Frame: 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. ]
   PK parameters will be derived using standard non-compartmental methods.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Japan

Research Site

Kashiwa, Japan, 277-8577

Research Site

Matsuyama-shi, Japan, 791-0280

Sponsors and Collaborators

AstraZeneca

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03394144
• Other Study ID Numbers: D5660C00017
• First Posted: January 9, 2018
• Last Update Posted: June 24, 2019
• Last Verified: June 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Durvalumab; Antineoplastic Agents, Immunological; Antineoplastic Agents