Clinical trial NCT02564900: Study of DS-8201a in Subjects With Advanced Solid Malignant Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Advanced solid tumors
phase 1
oncology
HER2
Antibody drug conjugate (ADC)
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
name: AstraZeneca
First posted: 2015-10-01
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label, two-part, multicenter study to evaluate the safety and tolerability of DS-8201a in participants with advanced solid malignant tumors.


Eligibility 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

Primary outcomes:
measure: Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
timeFrame: From 6 months postdose of last participant up to 3 years 5 months
Secondary outcomes:
measure: Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
timeFrame: From 6 months postdose of last participant up to 3 years 5 months
measure: Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
timeFrame: From 6 months postdose of last participant up to 3 years 5 months
measure: Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
timeFrame: From 6 months postdose of last participant up to 3 years 5 months
measure: Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
timeFrame: From 6 months postdose of last participant up to 3 years 5 months
measure: Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
timeFrame: From 6 months postdose of last participant up to 3 years 5 months
measure: Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
timeFrame: From 6 months postdose of last participant up to 3 years 5 months
measure: Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose
timeFrame: Post first dose up to Day 147
measure: Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose
timeFrame: Post first dose up to Day 147
measure: Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose
timeFrame: Post first dose up to Day 147
measure: Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose
timeFrame: Post first dose up to Day 147
measure: Overview of Treatment-emergent Adverse Events
timeFrame: Baseline up to 28 days after the last dose of study drug, up to 3 years 5 months
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: UC Health Clinical Trials Office
state: Ohio
city: Houston
country: United States
facility: University of Texas M. D. Anderson Cancer Center
state: Texas
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Kagoshima
country: Japan
facility: Social Medical Corporation Hakuaikai Sagara Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
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citation: Yin O, Iwata H, Lin CC, Tamura K, Watanabe J, Wada R, Kastrissios H, AbuTarif M, Garimella T, Lee C, Zhang L, Shahidi J, LaCreta F. Exposure-Response Relationships in Patients With HER2-Positive Metastatic Breast Cancer and Other Solid Tumors Treated With Trastuzumab Deruxtecan. Clin Pharmacol Ther. 2021 Oct;110(4):986-996. doi: 10.1002/cpt.2291. Epub 2021 Jun 10.
citation: 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.