Description:
This is a Phase I, open-label study to assess the safety, tolerability, pharmacokinetics and
anti-tumor activity of AZD4635 in Japanese patients with advanced solid malignancies. This
study consists of 2 cohorts, Cohort1 and Cohort2. At least 3 or up to 6 evaluable Japanese
patients with advanced solid malignancies will be enrolled in Cohort1 and 6 evaluable
patients will be enrolled in Cohort2.
Title
- Brief Title: A Phase I Study of AZD4635 in Japanese Patients With Advanced Solid Malignancies
- Official Title: A Phase I, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD4635 in Japanese Patients With Advanced Solid Malignancies.
Clinical Trial IDs
- ORG STUDY ID:
D8730C00005
- NCT ID:
NCT03980821
Conditions
- Advanced Solid Malignancies
Interventions
Drug | Synonyms | Arms |
---|
AZD4635 | | AZD4635 monotherapy |
Purpose
This is a Phase I, open-label study to assess the safety, tolerability, pharmacokinetics and
anti-tumor activity of AZD4635 in Japanese patients with advanced solid malignancies. This
study consists of 2 cohorts, Cohort1 and Cohort2. At least 3 or up to 6 evaluable Japanese
patients with advanced solid malignancies will be enrolled in Cohort1 and 6 evaluable
patients will be enrolled in Cohort2.
Detailed Description
Objectives:
Primary objective:
Investigate the safety and tolerability of AZD4635 monotherapy in Japanese patients
Secondary objective:
Characterize the single-dose and multiple-dose plasma pharmacokinetic (PK) parameters of
AZD4635 monotherapy Determine the preliminary anti-tumor activity of AZD4645 monotherapy
Overall design:
This is a phase I, open-label study of AZD4635 in Japanese patients with advanced solid
malignancies.
The study consists of 2 cohorts, Cohort 1 and Cohort 2. At least 3 or up to 6 evaluable
Japanese subjects with advanced solid malignancies will be enrolled in Cohort 1 and 6
evaluable patients will be required for Cohort 2 to confirm the tolerability. The total
number of evaluable subjects in each cohort will depend upon available data in each cohort
and decision of Safety Review Committee(SRC).
Study Period:
The study is expected to start in June 2019 and end in June 2020.
Number of Subjects:
9 to 12 evaluable subjects will be enrolled in this study to confirm the tolerability.
Treatments and treatment duration:
Subjects will receive AZD4635 once daily (QD). A single dose of AZD4635 will be taken on
Cycle 0 Day1 and the subsequent dose of AZD4635 will be taken from Cycle 1 Day 1 until
discontinuation criterion is met. A cycle of study treatment will be defined as 21 days of
continuous dosing.
Trial Arms
Name | Type | Description | Interventions |
---|
AZD4635 monotherapy | Experimental | Dose escalation of AZD4635 monotherapy for patients with advanced solid malignancies | |
Eligibility Criteria
Major Inclusion Criteria:
- Adult subjects; age ≥ 20 years
- Histologically or cytological confirmation of a solid, malignant tumor, excluding
central nervous system (CNS) tumors and lymphoma, that is refractory to standard
therapy or for which no standard of care regimen currently exists
- Patients must have either at least one lesion that can be evaluable using RECIST v1.1
or patients with mCRPC must have measurable prostate specific antigen above normal
limits (per local ranges)
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Normotensive or well controlled blood pressure, with or without current
antihypertensive treatment
- Females of child-bearing potential must use 2 highly effective methods of
contraception
- Male patients should be willing to use barrier contraception
Major Exclusion Criteria:
- Any investigational medicinal product or other systemic anticancer treatment within at
least 4 weeks prior to the first dose of study treatment, or within 8 weeks after
immunotherapy or other long half-life antibody therapy, whichever is the most
appropriate and as judged by the Investigator.
- Evidence of recent or significant cardiovascular disease
- Unresolved toxicities from prior therapy greater than CTCAE Grade 1 at starting study
treatment
- History of seizures, CNS tumors or CNS metastasis
- Active or prior documented autoimmune or inflammatory disorders within the past 3
years to the start of treatment
- Patients with prior ≥ Grade3 immune-mediated reactions
- Evidence of severe or uncontrolled systemic diseases
- Inadequate bone marrow reserve or organ function
- Refractory nausea and vomiting, chronic gastrointestinal diseases, or previous
significant bowel resection that would preclude adequate absorption of AZD4635
- History of hypersensitivity to AZD4635 or drugs with a similar chemical structure or
class to AZD4635
- Judgment by the Investigator that the patient should not participate in the study
Maximum Eligible Age: | 130 Years |
Minimum Eligible Age: | 20 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | The incidence of Adverse event and SAE |
Time Frame: | From the informed consent to 30 days post last dose |
Safety Issue: | |
Description: | Investigate the safety and tolerability of AZD4635 |
Secondary Outcome Measures
Measure: | Objective response rate (ORR) |
Time Frame: | Tumor assessment is Cycle 4 Day 1 and then on Day 1 of each even numbered cycle (+/-5 days) until disease progression. Expected to be for up to 6 months. |
Safety Issue: | |
Description: | Summarize based on RECIST 1.1 by cohort and overall. |
Measure: | Maximum plasma concentration (Cmax) |
Time Frame: | Samples will be collected at pre-specified time points in the single-dose and multiple-dose portion of the study beginning with Cycle 1 Day 1 until last dose. Expected to be for up to 6 months. |
Safety Issue: | |
Description: | Characterize the single-dose and multiple-dose plasma of AZD4635 |
Measure: | Disease control rate (DCR) |
Time Frame: | Tumor assessment is Cycle 4 Day 1 and then on Day 1 of each even numbered cycle (+/-5 days) until disease progression. Expected to be for up to 6 months. |
Safety Issue: | |
Description: | Summarize based on RECIST 1.1 by cohort and overall. |
Measure: | Area under the plasma concentration-time curve (AUC) |
Time Frame: | Samples will be collected at pre-specified time points in the single-dose and multiple-dose portion of the study beginning with Cycle 1 Day 1 until last dose. Expected to be for up to 6 months. |
Safety Issue: | |
Description: | Characterize the single-dose and multiple-dose plasma of AZD4635 |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | AstraZeneca |
Last Updated
December 8, 2020