This phase I trial identifies the side effects and best dose of DS-8201a and olaparib in treating patients with HER2-expressing cancers that have spread to other places in the body or cannot be removed by surgery or ovarian cancer that remains despite treatment with a platinum treatment (platinum resistant). Olaparib is a drug that blocks an enzyme involved in many cell functions, including the repair of deoxyribonucleic acid (DNA) damage. Blocking this enzyme may help keep tumor cells from repairing their damaged DNA, causing them to die. DS-8201a is an antibody-drug conjugate. This agent has two components: an antibody component and a chemotherapy component. The antibody component is attached to the chemotherapy molecules. Upon administration of DS-8201a, the antibody targets and binds to tumor cells that have abundant HER2 (human-epidermal growth factor receptor 2), which is a protein on the surface of some tumor cells. The chemotherapy then enters the cells and blocks DNA replication in the tumor cells with abundant HER2, causing them to die. Giving DS-8201a and olaparib may shrink or stabilize the cancer.
DOSE ESCALATION PHASE
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
HER2 1-3+ expression by IHC OR
HER2 amplification by next generation sequencing panel (NGS) or in situ hybridization (ISH) OR
Patients who have had chemotherapy (including antibody drug therapy) within 4 weeks with the following exceptions: 1 week for weekly paclitaxel; 2 weeks or five half-lives, whichever is longer, for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents, hormonal agents; or 6 weeks for nitrosoureas or mitomycin C
Patients who have had radiation therapy within 4 weeks
Patients who have had a major surgery within 4 weeks
Patients who are receiving any other investigational agents
National Cancer Institute (NCI)
Lead sponsor