Testing the Combination of DS-8201a and Olaparib in HER2-Expressing Cancers With Expansion in Patients With Platinum Resistant Ovarian Cancer

Recruiting now · Phase 1

Conditions studied: Metastatic Malignant Solid Neoplasm, Platinum-Resistant Ovarian High Grade Serous Adenocarcinoma, Unresectable Malignant Solid Neoplasm

In brief

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.

Key facts

Study ID

NCT04585958

Run by

National Cancer Institute (NCI)

People needed

55

Starts

2021-05-21

Expected to finish

2026-12-31

Last updated by the study team

2026-08-10

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 hybridization (ISH) OR
• If local testing is not feasible, patients will submit archival tissue for central HER2 testing to determine eligibility. Patients with unknown or negative HER2 testing will not be eligible
• Dose Escalation Module 3:
• HER2 1-2+ expression by IHC OR
• HER2 amplification by next generation sequencing panel (NGS) or in situ hybridization (ISH) OR
• If local testing is not feasible, patients will submit archival tissue for central HER2 testing to determine eligibility. Patients with unknown or negative HER2 testing will not be eligible
• DOSE EXPANSION PHASE
• Patients must have histologically confirmed platinum resistant, high grade serous ovarian carcinoma. Platinum resistant is defined as radiographic progression < 6 months following the last dose of platinum therapy
• HER2 IHC 1+ per local or central testing
• There must be least one lesion suitable for biopsy without significant risk to the patient
• Patient disease must be evaluable or measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Biopsiable lesion cannot be the only RECIST-measurable lesion
• DOSE ESCALATION AND DOSE EXPANSION PHASES
• Patients must have had at least one prior line of cytotoxic chemotherapy
• Patients can have received an unlimited number of additional lines of chemotherapy, targeted therapy, biologic therapy, or hormonal therapy
• Patients must have archival formalin-fixed paraffin-embedded (FFPE) tissue available for central confirmation of HER2 testing
• Age >= 18 years. Because no dosing or adverse event data are currently available on the use of DS-8201a in combination with olaparib in patients < 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• Hemoglobin >= 10.0 g/dL (within 21 days of randomization/enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
• Absolute neutrophil count >= 1,000/mcL (within 21 days of randomization/enrollment)

You may not qualify if…

• 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
• Patients with a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e. rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to DS-8201a, the inactive ingredients in the drug product, olaparib, or severe hypersensitivity to other monoclonal antibodies
• Patients receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP3A are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Patients with a medical history of myocardial infarction within 6 months before randomization/enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association class IIb to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to randomization
• Patients with a corrected QT interval (QTc) prolongation to > 470 ms (females) or > 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)
• Patients with multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, and other solid tumors curatively treated
• Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• Patients receiving chloroquine or hydroxychloroquine will require a washout period of >= 14 days to be eligible for the study
• Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade =< 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the investigator after consultation with the sponsor medical monitor or designee (e.g., grade 2 chemotherapy-induced neuropathy)
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because DS-8201a is a HER2 antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a. These potential risks may also apply to other agents used in this study
• Patients who have received a live, attenuated vaccine within 30 days prior to the first dose of DS-8201a

Where it is running

• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Coral Gables — Coral Gables, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Deerfield Beach — Deerfield Beach, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Doral — Doral, Florida, United States (enrolling)
• Mayo Clinic in Florida — Jacksonville, Florida, United States (enrolling)
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Kendall — Miami, Florida, United States (enrolling)
• UM Sylvester Comprehensive Cancer Center at Plantation — Plantation, Florida, United States (enrolling)
• Emory University Hospital Midtown — Atlanta, Georgia, United States (enrolling)
• Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States (enrolling)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
• Mayo Clinic in Rochester — Rochester, Minnesota, United States (enrolling)
• Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States

Full record on ClinicalTrials.gov

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