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 colorectal cancer

Phase 2 study of DS-8201a in subjects with colorectal cancer [DESTINY-CRC01]

86

The median age at informed consent was 58.5 years (range: 27 to 79). There were 46 (53.5%) male subjects and 40 (46.5%) female subjects. Most subjects were White (53 [61.6%]) or Asian (27 [31.4%]).

Enrolled: 86 enrolled (Cohort A: 53, Cohort B: 15, and Cohort C: 18) Each cohort is defined as below: Cohort A: HER2 IHC 3+ or IHC 2+/ISH +; Cohort B: HER2 IHC 2+/ISH -; Cohort C: HER2 IHC 1+ The 86 subjects enrolled in Cohorts A, B, or C received at least 1 dose of study drug.

Overall safety results for all cohorts are summarized below: - TEAEs were reported in 86/86 (100.0%) subjects. The most commonly reported TEAEs by PT (>=30% of subjects overall) were nausea, anaemia, fatigue, decreased appetite, platelet count decreased, vomiting, and neutrophil count decreased. - 8/86 (9.3%) subjects were adjudicated as study drug-related ILD.

The primary endpoint was confirmed ORR (the proportion of subjects who achieved a best overall response of CR or PR) assessed by the independent central imaging facility review in Cohort A. The confirmed ORR based on ICR was 45.3% (95% CI: 31.6, 59.6) with no subjects having a best overall response of CR and 24/53 subjects having best overall responses of PR.

The secondary and exploratory efficacy results of Cohort A (n = 53) are summarized below: - The median Duration of Response based on ICR was 7.0 months (95% CI: 5.8, 9.5). - The Disease Control Rate based on ICR was 83.0% (95% CI: 70.2, 91.9). - The median PFS was 6.9 months (95% CI: 4.1, 8.7). - The median OS was 15.5 months (95% CI: 8.8, 20.8). No responses were observed with low HER2-expressing mCRC in Cohort B (IHC 2+/ISH-) and Cohort C (IHC 1+): the confirmed ORR by ICR was 0% (95% CI: 0.0, 21.8) and 0% (95% CI: 0.0, 18.5), respectively.

Overall, DS-8201a demonstrated clinically meaningful response rates in subjects with HER2-overexpressing mCRC refractory to standard therapies. In the context of existing data available from current standard therapy in patient populations similar to those enrolled in this study, the efficacy and safety findings of this study warrant further development of DS-8201a in patients with HER2-overexpressing mCRC.

Mar. 04, 2021

https://www.sciencedirect.com/science/article/pii/S1470204521000863?via%3Dihub

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

Feb. 23, 2018

Interventional

multi center, open-label, 3-cohort study

treatment purpose

2

- Age >= 20 years in Japan, >= 18 years in the rest of the countries.
- Pathologically documented unresectable, recurrent, or metastatic colorectal adenocarcinoma. Until sponsor's notification to the study sites, subject must be a RAS/BRAF wild-type cancer.
- Received at least 2 prior regimens of standard treatment.
- Has measurable disease assessed by the investigator based on RECIST version 1.1.
- Has an ECOG PS of 0 to 1

- Medical history of myocardial infarction within 6 months, symptomatic congestive heart failure
- Has a medical history of clinically significant lung disease
- Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy

Both

Colorectal cancer

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 : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

efficacy
The objective response rate
RECIST Version 1.1

efficacy
pharmacokinetics
Progression-free survival, Overall survival, Duration of response, Disease control rate, Safety, Pharmacokinetic
RECIST Version 1.1

Nov. 21, 2017