Clinical trial NCT04458272: A Study 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: WHO Grade II Glioma
Keywords: DS-1001
IDH1
Glioma
IDH-mutant glioma
WHO grade II glioma
Low-grade glioma
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2020-07-07
Enrollment: 25
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall response rate (ORR) assessed by Independent Efficacy Review Committee
timeFrame: Up to 24 months
measure: Number of participants with treatment-emergent adverse events (TEAEs) during the study
timeFrame: Up to 24 months
Secondary outcomes:
measure: Clinical benefit rate
timeFrame: Through the end of the study (up to approximately 6 years)
measure: Percentage change in tumor volume
timeFrame: Through the end of the study (up to approximately 6 years)
measure: Time to response
timeFrame: Through the end of the study (up to approximately 6 years)
measure: Duration of response
timeFrame: Through the end of the study (up to approximately 6 years)
measure: Time to treatment failure
timeFrame: Through the end of the study (up to approximately 6 years)
measure: Progression-free survival
timeFrame: Through the end of the study (up to approximately 6 years)
measure: Overall survival
timeFrame: Through the end of the study (up to approximately 6 years)
measure: Area under the concentration curve (AUC) for DS-1001a
timeFrame: Cycle 1 Day 1 to Cycle 13 Day 1 (each cycle is 28 days)
measure: Maximum plasma concentration (Cmax) for DS-1001a
timeFrame: Cycle 1 Day 1 to Cycle 13 Day 1 (each cycle is 28 days)
measure: Time to maximum plasma concentration (Tmax) for DS-1001a
timeFrame: Cycle 1 Day 1 to Cycle 13 Day 1 (each cycle is 28 days)
measure: Change from baseline in 2-hydroxyglutarate (2-HG) concentration in patient specimens after treatment with DS-1001b
timeFrame: Through the end of the study (up to approximately 6 years)
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Sagamihara
country: Japan
facility: Kitasato University Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Tokyo
country: Japan
facility: Kyorin University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Study Leader
role: STUDY_DIRECTOR
References:
citation: 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.