Actively Recruiting

Phase 1
Age: 18Years +
All Genders
NCT04585958

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

Led by National Cancer Institute (NCI) · Updated on 2026-05-13

55

Participants Needed

5

Research Sites

292 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Patients must have histologically confirmed metastatic or unresectable malignancy without effective standard treatments
  • Tumors must express HER2 by immunohistochemistry (IHC) or show HER2 gene amplification by next generation sequencing or in situ hybridization
  • Patients with platinum-resistant high grade serous ovarian carcinoma with disease progression within 6 months after last platinum therapy
  • At least one lesion suitable for biopsy without significant risk
  • Disease must be evaluable or measurable by RECIST 1.1 criteria
  • Patients must have had at least one prior line of cytotoxic chemotherapy
  • Archival tissue must be available for central HER2 testing confirmation
  • Age 18 years or older
  • ECOG performance status of 0 or 1 (Karnofsky score ≥ 70%)
  • Hemoglobin ≥ 10.0 g/dL without recent transfusions
  • Absolute neutrophil count ≥ 1,000/mcL without recent granulocyte colony-stimulating factor use
  • Platelets ≥ 100,000/mcL without recent transfusions
  • Total bilirubin ≤ 1.5 times institutional upper limit of normal, or ≤ 3 times with Gilbert's syndrome or liver metastases
  • AST/ALT ≤ 3 times institutional upper limit of normal
  • Creatinine ≤ 1.5 times institutional upper limit or glomerular filtration rate ≥ 51 mL/min/1.73 m²
  • Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan
  • HIV positive patients must be stable, with undetectable viral load and CD4 count ≥ 250, no recent opportunistic infections
  • Hepatitis B patients must have undetectable viral load if on suppressive therapy
  • Hepatitis C patients must be cured or have undetectable viral load if on treatment
  • Stable brain metastases off steroids and radiation at least 4 weeks prior
  • Patients with prior or concurrent malignancies without interference on study assessment
  • Cardiac function better than New York Heart Association class 2B
  • Women of child-bearing potential and men must agree to use contraception during and after treatment
  • Women of non-child-bearing potential defined by surgery or menopause
  • Male subjects must not donate or freeze sperm during study and for 4 months after
  • Female subjects must not donate or retrieve eggs during study and for 7 months after
  • Ability to understand and sign informed consent or have legally authorized representative
Not Eligible

You will not qualify if you...

  • Chemotherapy within 4 weeks prior to study with certain exceptions for weekly or small-molecule agents
  • Radiation therapy within 4 weeks prior to study
  • Major surgery within 4 weeks prior to study
  • Receiving other investigational agents
  • History or current interstitial lung disease or pneumonitis requiring steroids
  • Severe pulmonary compromise or autoimmune disorders affecting lungs
  • Allergic reactions to DS-8201a, olaparib, or similar agents
  • Use of moderate or strong inhibitors or inducers of CYP3A
  • Myocardial infarction within 6 months, symptomatic congestive heart failure, or elevated troponin levels
  • Corrected QT interval prolongation above specified thresholds
  • Multiple primary malignancies within 3 years except certain treated cancers
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
  • Use of chloroquine or hydroxychloroquine without 14-day washout
  • Unresolved toxicities from prior anticancer therapy above grade 1 except alopecia
  • Psychiatric or social conditions limiting study compliance
  • Pregnant or breastfeeding women
  • Receipt of live attenuated vaccine within 30 days prior to first dose of DS-8201a

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 5 locations

1

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States, 85054

Active, Not Recruiting

2

Mayo Clinic in Florida

Jacksonville, Florida, United States, 32224-9980

Actively Recruiting

3

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Actively Recruiting

4

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Actively Recruiting

5

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States, 15232

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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