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

NCT04585958 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2020-0784110355UM1CA186709
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Unresectable Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; Platinum-Resistant Ovarian High Grade Serous Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose/recommended phase 2 dose

  Will be measured by Common Terminology Criteria for Adverse Events version (v) 5.0 and analyzed using descriptive statistics.

  Up to 42 days

• Incidence of adverse events

  Up to 30 days post treatment

Secondary Outcomes (6)

• Objective response rate (ORR)

  Up to 30 days post treatment

• Clinical benefit rate (CBR)

  Up to 30 days post treatment

• Duration of response (DOR)

  Up to 30 days post treatment

• HER2 expression

  At baseline

• Plasma pharmacokinetic (PK) profiles

  Up to 30 days post treatment

Other Outcomes (5)

• HER2 expression

  Up to 30 days post treatment

• Formation of topoisomerase I cleaved complex formation (TOP1cc) in blood samples

  Up to 30 days post treatment

• Presence of topoisomerase I cleaved complex formation (TOP1cc) in paired on-treatment tumor specimens

  Up to 30 days post treatment

Study Arms (1)

Treatment (trastuzumab deruxtecan, olaparib)

EXPERIMENTAL

Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 and olaparib PO BID on days 1-21, days 8-14, or days 3-9 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients undergo collection of blood samples, ECHO or MUGA, CT, and biopsies throughout the trial.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Drug: Olaparib; Biological: Trastuzumab Deruxtecan

Interventions

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Treatment (trastuzumab deruxtecan, olaparib)

Trastuzumab Deruxtecan BIOLOGICAL

Given IV

Also known as: DS-8201, DS-8201a, Enhertu, Fam-trastuzumab Deruxtecan-nxki, T-DXd, WHO 10516

Treatment (trastuzumab deruxtecan, olaparib)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (trastuzumab deruxtecan, olaparib)

Biospecimen Collection PROCEDURE

Undergo collection of blood and urine samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (trastuzumab deruxtecan, olaparib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (trastuzumab deruxtecan, olaparib)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (trastuzumab deruxtecan, olaparib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281

Treatment (trastuzumab deruxtecan, olaparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

ACTIVE NOT RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Biopsy; Specimen Handling; olaparib; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Elizabeth K Lee

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: October 14, 2020
• Study Start: May 21, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 13, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (5)