A Phase I Study of DS-8201a in Combination With Olaparib in HER2-Expressing Malignancies
National Cancer Institute (NCI)
Summary
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.
Description
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…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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 hybridizati…
Interventions
- ProcedureBiopsy Procedure
Undergo biopsy
- ProcedureBiospecimen Collection
Undergo collection of blood and urine samples
- ProcedureComputed Tomography
Undergo CT
- ProcedureEchocardiography Test
Undergo echocardiography
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- DrugOlaparib
Given PO
- BiologicalTrastuzumab Deruxtecan
Locations (5)
- Mayo Clinic Hospital in ArizonaPhoenix, Arizona
- Mayo Clinic in FloridaJacksonville, Florida
- Dana-Farber Cancer InstituteBoston, Massachusetts
- Mayo Clinic in RochesterRochester, Minnesota
- University of Pittsburgh Cancer Institute (UPCI)Pittsburgh, Pennsylvania