臨床研究等提出・公開システム

A Phase 2, multicenter, open-label study of DS-8201a in subjects with HER2-expressing advanced gastric or gastroesophageal junction adenocarcinoma

Phase 2 study of DS-8201a in subjects with gastric cancer [DESTINY-Gastric01]

233

Primary cohort: 142 (75.9%) subjects (95 [76.0%] in the DS-8201a group and 47 [75.8%] in the physician's choice group) were male. The median age of the subjects was 66.0 years (65.0 in the DS-8201a group and 66.0 in the physician's choice group). Exploratory cohort: 16 (80.0%) subjects in Exploratory Cohort 1 and 17 (70.8%) subjects in Exploratory Cohort 2 were male. The median age of the subjects was 64.0 years in Exploratory Cohort 1 and 58.5 years in Exploratory Cohort 2. (last subject last follow-up date was 11 Dec 2020)

Primary Cohort: Randomized subjects: 188 (DS-8201a: 126, physician's choice treatment: 62) Subjects treated with study drug (Full analysis set, Safety analysis set): 187 (DS-8201a: 125, physician's choice treatment: 62 [Irinotecan: 55, Paclitaxel: 7]) Response Evaluable Set (RES): 175 (DS-8201a: 119, physician's choice treatment: 56). Exploratory Cohort: Cohort 1: Enrolled subjects: 21 Subjects treated with study drug: 20 RES: 19 Cohort 2: Enrolled subjects: 24 Subjects treated with study drug: 24 RES: 23

Primary Cohort: Among 187 subjects who were included in the safety analysis set, TEAEs were reported in 125 (100.0%) subjects in the DS-8201a group and 61 (98.4%) subjects in the physician's choice group. Grade >=3 TEAEs were reported in 107 (85.6%) subjects in the DS-8201a group and 35 (56.5%) subjects in the physician's choice group. Serious TEAEs were reported in 58 (46.4%) subjects in the DS-8201a group and 16 (25.8%) subjects in the physician's choice group. The most commonly reported TEAEs in Primary cohort by PT (>=30% of subjects in any of the treatment groups) were: nausea (DS-8201a: 63.2%, physician's choice treatment: 46.8%), neutrophil count decreased (63.2%, 33.9%), decreased appetite (60.8%, 45.2%), anaemia (56.8%, 30.6%), white blood cell count decreased (39.2%, 33.9%), platelet count decreased (38.4%, 6.5%), malaise (35.2%, 16.1%), and diarrhoea (32.8%, 32.3%). The majority of the most commonly reported TEAEs in the DS-8201a group were gastrointestinal or hematologic AEs. In DS-8201a group, 17 (13.6%) subjects had events that were adjudicated as drug-related interstitial lung disease (ILD)/pneumonitis events by the ILD Adjudication Committee. Among these subjects, Grade 1 in 4 (3.2%) subjects, Grade 2 in 9 (7.2%) subjects, Grade 3 in 2 (1.6%) subjects, Grade 4 in 1 (0.8%) subject, and Grade 5 in 1 (0.8%) subject. Exploratory Cohort: Twenty (100.0%) subjects of Exploratory Cohort 1 and 24 (100.0%) subjects of Exploratory Cohort 2 experienced at least 1 TEAE. The safety profiles of the Exploratory Cohorts were similar to that of the DS-8201a group in the Primary Cohort.

In the RES, the ORR based on ICR in Primary cohort was 51.3% (95% CI: 41.9, 60.5) in the DS-8201a group and 14.3% (95% CI: 6.4, 26.2) in the physician's choice group.

Primary cohort: In the RES, The confirmed ORR based on ICR was 42.0% (95% CI: 33.0, 51.4) in the DS-8201a group and 12.5% (95% CI: 5.2, 24.1) in the physician's choice group. The median OS was 12.6 months (95% CI: 10.3, 15.4) in the DS-8201a group and 8.9 months (95% CI: 6.4, 10.4) in the physician's choice group. The stratified OS hazard ratio (HR) was 0.69 (95% CI: 0.49, 0.97). The median PFS by ICR was 5.6 months (95% CI: 4.3, 6.9) in the DS-8201a group vs. 3.5 months (95% CI: 2.0, 4.3) in the physician's choice group. The stratified HR for PFS was 0.47 (95% CI: 0.31, 0.71). The median Duration of Response for confirmed responses based on ICR was 12.7 months (95% CI: 5.6, 21.1) in the DS-8201a group vs. 3.9 months (95% CI: 3.0, 4.9) in the physician's choice group. Exploratory cohort: In the RES, the confirmed ORR based on ICR was 26.3% (95% CI: 9.1, 51.2) for Exploratory Cohort 1 and 9.5% (95% CI: 1.2, 30.4) for Exploratory Cohort 2.

The efficacy and safety findings of this study demonstrated the positive benefit/risk ratio of DS-8201a in HER2 positive patients with advanced gastric or GEJ adenocarcinoma who have progressed on 2 or more regimens including fluoropyrimidine agent, platinum agent, and trastuzumab. DS-8201a demonstrated antitumor activity in patients with HER2-low (IHC 2+/ISH-, IHC 1+) advanced gastric or GEJ adenocarcinoma

June. 18, 2020

https://www.nejm.org/doi/full/10.1056/NEJMoa2004413

Yes

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/ Supporting Documents: - Study Protocol - Statistical Analysis Plan - Clinical Study Report 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. 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. URL: https://vivli.org/ourmember/daiichi-sankyo/

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Nov. 02, 2017

Interventional

multi center, open-label, 3-cohort study

treatment purpose

2

- Has a pathologically documented locally advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction.
- Progression on and after at least 2 prior regimens which had to include a fluoropyrimidine and a platinum.
- Has measurable disease assessed by the investigator based on RECIST version 1.1.
- Has an ECOG PS of 0 to 1

- Has a medical history of clinically significant lung disease
- Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy
- Has had non-gastric or gastroesophageal junction primary malignancies within 3 years

Both

Gastric or gastroesophageal junction adenocarcinoma

investigational material(s)
Generic name etc : DS-8201a
INN of investigational material : trastuzumab deruxtecan
Therapeutic category code : 42- Antineoplastic agents
Dosage and Administration for Investigational material : IV solution (Once every 3 weeks, 6.4 mg/kg)

control material(s)
Generic name etc : irinotecan (Physician's Choice Treatment : irinotecan or paclitaxel)
INN of investigational material : irinotecan
Therapeutic category code : 424 Antineoplastic preparations extracted from plants
Dosage and Administration for Investigational material : Irinotecan: IV solution (150 mg/m2)
Generic name etc : paclitaxel (Physician's Choice Treatment : irinotecan or paclitaxel)
INN of investigational material : paclitaxel
Therapeutic category code : 424 Antineoplastic preparations extracted from plants
Dosage and Administration for Investigational material : Paclitaxel: IV solution (80 mg/m2)

efficacy
The objective response rate
RECIST Version 1.1

safety
efficacy
pharmacokinetics
Progression-free survival, Overall survival, Duration of response, Disease control rate, Time to treatment failure, Safety, Pharmacokinetic
RECIST Version 1.1

Sept. 27, 2017