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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: WHO Grade II Glioma
• Intervention / Treatment: Drug: DS-1001b

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Hiroshima, Japan
    • Hiroshima University Hospital
  • Kumamoto, Japan
    • Kumamoto University Hospital
  • Kyoto, Japan
    • Kyoto University Hospital
  • Osaka, Japan
    • National Hospital Organization Osaka National Hospital
  • Tokyo, Japan
    • Kyorin University Hospital
  • Tokyo, Japan
    • National Cancer Center Hospital
  • Tokyo, Japan
    • Tokyo Women's Medical University Hospital
  • Aichi
    • Nagoya, Aichi, Japan
      • Nagoya University Hospital
  • Kanagawa
    • Sagamihara, Kanagawa, Japan
      • Kitasato University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan
      • Tohoku University Hospital
  • Saitama
    • Hidaka, Saitama, Japan
      • Saitama Medical University International Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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: DS-1001b	Drug: DS-1001b; 250 mg, twice daily, continuous oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Investigators: Study Director: Clinical Study Leader, Daiichi Sankyo, Inc.

Publications and helpful links

General Publications

• Natsume A, Arakawa Y, Narita Y, Sugiyama K, Hata N, Muragaki Y, Shinojima N, Kumabe T, Saito R, Motomura K, Mineharu Y, Miyakita Y, Yamasaki F, Matsushita Y, Ichimura K, Ito K, Tachibana M, Kakurai Y, Okamoto N, Asahi T, Nishijima S, Yamaguchi T, Tsubouchi H, Nakamura H, Nishikawa R. The first-in-human phase I study of a brain-penetrant mutant IDH1 inhibitor DS-1001 in patients with recurrent or progressive IDH1-mutant gliomas. Neuro Oncol. 2023 Feb 14;25(2):326-336. doi: 10.1093/neuonc/noac155.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2020
• Primary Completion (Actual): March 10, 2023
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: July 2, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Glioma; IDH1; DS-1001; IDH-mutant glioma; WHO grade II glioma; Low-grade glioma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: DS1001-A-J201; 205339 (Other Identifier: JapicCTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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