Study of DS-8201a in Subjects With Advanced Solid Malignant Tumors

• ClinicalTrials.gov Identifier: NCT02564900
• Recruitment Status: Active, not recruiting
• First Posted: October 1, 2015
• Last Update Posted: August 9, 2019
• Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborators: Daiichi Sankyo, Inc.; AstraZeneca
• Information provided by (Responsible Party): Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Study Description

Brief Summary:

This is an open-label, two-part, multiple study to evaluate the safety and tolerability of DS-8201a in patients with advanced solid malignant tumors.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Drug: DS-8201a	Phase 1

Detailed Description:

This study is one single group of participants in two periods. It is therefore not randomized. The dosage strength will change during the study but all participants will receive the same study drug DS-8201a. So the study is not a true 2 arm study, it is a 2 part study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 278 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1, Two-Part, Multicenter, Non-randomized, Open-label, Multiple Dose First-In-Human Study of DS-8201A, in Subjects With Advanced Solid Malignant Tumors
• Study Start Date: August 2015
• Estimated Primary Completion Date: March 2020
• Estimated Study Completion Date: March 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1 Dose escalation; Part 1 is a dose escalation to identify the Maximum Tolerated dose (MTD) or the recommended phase 2 dose of DS-8201a guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation with overdose control principal.	Drug: DS-8201a
Experimental: Part 2 Dose expansion; Part 2 is a dose expansion to examine the safety and efficacy of DS-8201a and it is consist of multiple cohorts: in subjects with trastuzumab emtansine (T-DM1)-treated HER2 overexpressing breast cancer (Part 2a); trastuzumab-treated HER2 overexpressing gastric or gastroesophageal junction adenocarcinoma (Part 2b); HER2 low expressing breast cancer (Part 2c), and HER2 expressing other solid malignant tumor (Part 2d)	Drug: DS-8201a

Outcome Measures

Primary Outcome Measures :

1. Number of subjects experiencing adverse events [ Time Frame: Day 1 through 28 days after last dose ]
   frequency and seriousness of treatment emergent adverse events (TEAEs).
2. Tumor response using RECIST version 1.1 throughout study [ Time Frame: from randomization date until disease progresses, whichever comes first, up to 30 months ]
   RECIST = Response Evaluation Criteria In Solid Tumors Assessment of tumor response is conducted every 6 weeks in the first 24 weeks and thereafter every 12 weeks until progressive disease to evaluate the efficacy of DS-8201a up to 30 months.

Secondary Outcome Measures :

1. Change in the area under curve (AUC) of DS-8201a [ Time Frame: from first dose to Day 45 ]
   area under curve AUC at Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.
2. Change in the maximum plasma concentration (Cmax) of DS-8201a [ Time Frame: from first dose to Day 45 ]
   maximum plasma concentration Cmax at Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.
3. Change in the time of maximum plasma concentration (Tmax) of DS-8201a [ Time Frame: from first dose to Day 45 ]
   time of maximum plasma concentration Tmax at Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.
4. Change in the total anti-HER2 antibody [ Time Frame: from first dose to Day 45 ]
   Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.
5. Change in MAAA-1181 level [ Time Frame: from first dose to Day 45 ]
   determine the change in MAAA-1181 level from first dose to Day 45 at Cycle 1, Days 1, 2, 4, 8, 15; Cycles 2, 4, 6, and 8, Day 1; Cycle 3, Days 1, 8, 15.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group performance status( PS) of 0 or 1.
• Left Ventricular Ejection Fraction (LVEF) ≥ 50%

Part 1:

• Advanced/unresectable or metastatic breast cancer or gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.

Part 2a:

• Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
• Treated with ado-trastuzumab emtansine (T-DM1)

Part 2b:

• Advanced gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
• Treated with trastuzumab

Part 2c:

• Advanced breast cancer with HER2 low expression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.

Part 2d:

• Satisfy at least one of the following criteria

  1. Advanced/unresectable or metastatic solid malignant tumor with HER2 expression other than breast cancer and gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
  2. Advanced/unresectable or metastatic tumor with HER2 mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.

Part 2e:

• Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
• Treated with ado-trastuzumab emtansine (T-DM1) (patients with HER2 overexpression only)

Exclusion Criteria:

• Has a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia.
• Has a medical history of myocardial infarction or unstable angina.
• Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females.
• Has a medical history of clinically significant lung diseases

Contacts and Locations

Locations

United States, California

Sharp Memorial Hospital

San Diego, California, United States, 92123

United States, Florida

Mayo Clinic

Jacksonville, Florida, United States, 32224

United States, Kentucky

University of Louisville

Louisville, Kentucky, United States, 40202

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

United States, Ohio

UC Health Clinical Trials Office

Cincinnati, Ohio, United States, 45229

United States, Texas

University of Texas M. D. Anderson Cancer Center

Houston, Texas, United States, 77030-3721

Japan

Aichi Cancer Center Hospital

Aichi, Japan

National Cancer Center Hospital East

Chiba, Japan

Social Medical Corporation Hakuaikai Sagara Hospital

Kagoshima, Japan

Kindai University Hospital

Osaka, Japan

National Cancer Center Hospital

Tokyo, Japan

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Tokyo, Japan

Sponsors and Collaborators

Daiichi Sankyo Co., Ltd.

Daiichi Sankyo, Inc.

AstraZeneca

Investigators

• Study Director: Global Clinical Leader; Daiichi Sankyo, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, Krop IE, Lee C, Fujisaki Y, Sugihara M, Zhang L, Shahidi J, Takahashi S. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol. 2020 Jun 10;38(17):1887-1896. doi: 10.1200/JCO.19.02318. Epub 2020 Feb 14.

Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, Tsurutani J, Kadowaki S, Yamaguchi K, Iwasa S, Saito K, Fujisaki Y, Sugihara M, Shahidi J, Doi T. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):827-836. doi: 10.1016/S1470-2045(19)30088-9. Epub 2019 Apr 29. Erratum in: Lancet Oncol. 2019 May 10;:.

Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29. Erratum in: Lancet Oncol. 2019 May 10;:.

Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, Shimizu C, Shimoi T, Kuboki Y, Matsubara N, Kitano A, Jikoh T, Lee C, Fujisaki Y, Ogitani Y, Yver A, Tamura K. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017 Nov;18(11):1512-1522. doi: 10.1016/S1470-2045(17)30604-6. Epub 2017 Oct 13.

• Responsible Party: Daiichi Sankyo Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02564900
• Other Study ID Numbers: DS8201-A-J101; 152978 ( Registry Identifier: JAPIC CTI )
• First Posted: October 1, 2015
• Last Update Posted: August 9, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: 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 Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• 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/

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):

Advanced solid tumors; phase 1; oncology; HER2; Antibody drug conjugate (ADC)

Additional relevant MeSH terms:

Neoplasms