A Study of DS-1001b in Patients With Chemotherapy- and Radiotherapy-Naive IDH1 Mutated WHO Grade II Glioma

Study Overview
=================
Brief Summary
-----------------
This Phase 2 study is conducted to assess the efficacy and safety of DS-1001b in patients with chemotherapy- and radiotherapy-naive IDH1 mutated WHO grade II glioma.

Official Title
-----------------
A Phase II Study of DS-1001b in Patients With Chemotherapy- and Radiotherapy-naive IDH1 Mutated WHO Grade II Glioma

Conditions
-----------------
WHO Grade II Glioma

Intervention / Treatment
-----------------
* Drug: DS-1001b


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has a histopathologically documented IDH1 mutated WHO grade II glioma according to the 2016 WHO classification. Has confirmed IDH1 mutation at the R132 locus by testing at the central laboratory conducted during the screening period. Has no prior anticancer treatment (including chemotherapy and radiotherapy) for glioma except craniotomy or biopsy. Has at least 1 measurable and non-enhancing lesion. Has an interval of at least 90 days from the latest surgery. Has no sign of malignant transformation including the appearance of enhancing lesions and/or rapid growth of non-enhancing lesions. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1. Exclusion Criteria: Has had a histopathological diagnosis of WHO grade III or IV glioma. Has had a contrast enhancing lesion on brain MRI. Has received a prior treatment with any mutant IDH1 inhibitor. Has received other investigational products within 28 days before the start of the study drug treatment. Has an active infection requiring systemic treatment. Has multiple primary malignancies. Has a history of clinically significant cardiac disease. Is a pregnant or lactating woman.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DS-1001b<br> | Drug: DS-1001b<br>* 250 mg, twice daily, continuous oral administration<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) assessed by Independent Efficacy Review Committee |  | Up to 24 months | 
| Number of participants with treatment-emergent adverse events (TEAEs) during the study |  | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate |  | Through the end of the study (up to approximately 6 years) | 
| Percentage change in tumor volume |  | Through the end of the study (up to approximately 6 years) | 
| Time to response |  | Through the end of the study (up to approximately 6 years) | 
| Duration of response |  | Through the end of the study (up to approximately 6 years) | 
| Time to treatment failure |  | Through the end of the study (up to approximately 6 years) | 
| Progression-free survival |  | Through the end of the study (up to approximately 6 years) | 
| Overall survival |  | Through the end of the study (up to approximately 6 years) | 
| Area under the concentration curve (AUC) for DS-1001a |  | Cycle 1 Day 1 to Cycle 13 Day 1 (each cycle is 28 days) | 
| Maximum plasma concentration (Cmax) for DS-1001a |  | Cycle 1 Day 1 to Cycle 13 Day 1 (each cycle is 28 days) | 
| Time to maximum plasma concentration (Tmax) for DS-1001a |  | Cycle 1 Day 1 to Cycle 13 Day 1 (each cycle is 28 days) | 
| Change from baseline in 2-hydroxyglutarate (2-HG) concentration in patient specimens after treatment with DS-1001b |  | Through the end of the study (up to approximately 6 years) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DS-1001, IDH1, Glioma, IDH-mutant glioma, WHO grade II glioma, Low-grade glioma