Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer

Primary Objectives 1. To assess the safety and tolerability of DS-8201a Secondary Objectives 1. To assess the PK profiles of DS-8201a, total anti-HER2 antibody, and MAAA-1181a 2. To investigate the anti-tumor activity of DS-8201a 3. To assess the incidence of anti-drug antibodies (ADA) against DS-8201a

DS-8201a

DS-8201a

Lyophilized powder

100

Primary Endpoints
Safety endpoints:
• Safety endpoints will include serious adverse events (SAEs), TEAEs, AEs and
AESIs leading to discontinuation.
• Other safety endpoints will include physical examination findings (including
Eastern Cooperative Oncology Group Performance Status [ECOG PS]), vital
sign measurements, standard clinical laboratory parameters, ECG parameters,
ECHO or MUGA findings, and ophthalmologic findings. TEAEs will be
graded according to the National Cancer Institute Common Terminology
Criteria for Adverse Events (NCI-CTCAE) version 4.03.

PK endpoints:
• Serum concentration data at each time point and PK parameters of DS–8201a,
total anti-HER2 antibody, and MAAA-1181a will be presented.

Efficacy endpoints:
Tumor response will be evaluated by the Investigators using Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1:
• ORR
• DCR
• Duration of response (DoR)
• Progression-free survival (PFS)
• Overall survival (OS)
• Best percentage change in the sum of diameter(s) of target lesion(s)

Inclusion Criteria:

Has a pathologically documented unresectable or metastatic gastric or GEJ adenocarcinoma, or breast cancer, with HER2 expression [immunohistochemistry (IHC) 3+, 2+, or 1+ and/or in situ hybridization (ISH) +] that is refractory to or intolerable with standard treatment, or for which no standard treatment is available
Has a left ventricular ejection fraction (LVEF) ≥ 50%
Has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1

Exclusion Criteria:

Has a medical history of myocardial infarction within 6 months before enrollment
Has a medical history of ventricular arrhythmias, other than rare occasional premature ventricular contractions
Has uncontrolled or significant cardiovascular disease
Has any other history or condition that might compromise:

Safety of the participant or offspring
Safety of study staff
Analysis of Results