National Cancer Institute (NCI)
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). 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 deoxyribonucleic acid (DNA) replication in the tumor cells with abundant HER2, causing them to die. Olaparib is a drug that blocks an enzyme involved in many cell functions, including the repair of DNA damage. Blocking this enzyme may help keep tumor cells from repairing their damaged DNA, causing them to die. Giving DS-8201a and olaparib may shrink or stabilize the cancer.
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of the combination of trastuzumab deruxtecan (DS-8201a) in combination with olaparib, and to determine the recommended phase 2 dose (RP2D). II. To evaluate the safety and tolerability of this combination in a dose expansion cohort in patients with platinum resistant high grade serous ovarian carcinoma. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity as measured by objective response rate (ORR), clinical benefit rate, progression-free survival (PFS), and duration of response (DoR). II. To measure baseline HER…
Inclusion Criteria: * 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 * Patients must have HER2-positive or HER2-expressing tumors determined by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory. Specific requirement of HER2 status is outlined below: * Dose Escalation Module 1 and Module 2: * HER2 1-3+ expression by IHC OR * HER2 amplification by next generation sequencing panel (NGS) or in situ hybridizat…
Undergo biopsy
Undergo collection of blood samples
Undergo CT
Undergo echocardiography
Undergo MUGA
Given PO
Given IV