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

Daiichi Sankyo

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: DS-8201a (DP); Drug: DS-8201a (DP1); Drug: DS-8201a (DP2)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02564900

152978 (Registry Identifier)

DS8201-A-J101

Details and patient eligibility

About

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.

Enrollment: 292 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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292 participants in 2 patient groups

Part 1 Dose escalation

Experimental group

Description:

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.

Treatment:

Drug: DS-8201a (DP)

Drug: DS-8201a (DP1)

Part 2 Dose expansion

Experimental group

Description:

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), HER2 expressing other solid malignant tumor (Part 2d); HER2 expressing breast cancer (Japan only; Part 2e)

Treatment:

Drug: DS-8201a (DP)

Drug: DS-8201a (DP1)

Drug: DS-8201a (DP2)