Ignite Creation Date:
2025-12-24 @ 11:57 PM
Ignite Modification Date:
2025-12-25 @ 9:54 PM
Study NCT ID:
NCT04585958
Status:
RECRUITING
Last Update Posted:
2025-12-24
First Post:
2020-10-13
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Testing the Combination of DS-8201a and Olaparib in HER2-Expressing Cancers With Expansion in Patients With Platinum Resistant Ovarian Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I Study of DS-8201a in Combination With Olaparib in HER2-Expressing Malignancies
Status:
RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
Detailed 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 HER2 expression by immunohistochemistry (IHC) in a central laboratory and correlate with response in the dose escalation and in the dose expansion.
III. To evaluate the plasma pharmacokinetic (PK) profiles of olaparib and DS-8201a metabolites when administered in combination in the dose escalation and in the dose expansion.
IV. To determine markers of DNA damage response (DDR) in tumor specimens at baseline and on-treatment in patients with platinum resistant high grade serous ovarian carcinoma in dose expansion.
EXPLORATORY OBJECTIVES:
I. To measure baseline HER2 expression by immune multiple reaction monitoring-mass spectroscopy (ImmunoMRM), and correlate with baseline central IHC and with response in dose escalation and in dose expansion.
II. To assess the formation of topoisomerase I cleaved complex formation (TOP1cc) in blood specimens and correlate with response in dose escalation and in dose expansion.
III. To assess the formation of TOP1cc in paired on-treatment tumor specimens (after DS-8201a alone and after DS-8201a and olaparib combination) and correlate with response in patients with platinum resistant high grade serous ovarian carcinoma in the expansion.
IV. To measure changes in HER2 expression over the course of treatment by IHC and immune multiple reaction monitoring-mass spectrometry (immunoMRM) and correlate with response in patients with platinum resistant high grade serous ovarian carcinoma in dose expansion.
V. To determine biomarkers of response and resistance in tumor specimens and blood specimens, including whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing.
OUTLINE: This is a dose-escalation study of trastuzumab deruxtecan in combination with olaparib followed by a dose-expansion study.
Patients receive trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1 and olaparib orally (PO) twice daily (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, echocardiography (ECHO) or multigated acquisition scan (MUGA), computed tomography (CT), and biopsies throughout the trial.
After completion of study treatment, patients are followed up for 30 days.
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 HER2 expression by immunohistochemistry (IHC) in a central laboratory and correlate with response in the dose escalation and in the dose expansion.
III. To evaluate the plasma pharmacokinetic (PK) profiles of olaparib and DS-8201a metabolites when administered in combination in the dose escalation and in the dose expansion.
IV. To determine markers of DNA damage response (DDR) in tumor specimens at baseline and on-treatment in patients with platinum resistant high grade serous ovarian carcinoma in dose expansion.
EXPLORATORY OBJECTIVES:
I. To measure baseline HER2 expression by immune multiple reaction monitoring-mass spectroscopy (ImmunoMRM), and correlate with baseline central IHC and with response in dose escalation and in dose expansion.
II. To assess the formation of topoisomerase I cleaved complex formation (TOP1cc) in blood specimens and correlate with response in dose escalation and in dose expansion.
III. To assess the formation of TOP1cc in paired on-treatment tumor specimens (after DS-8201a alone and after DS-8201a and olaparib combination) and correlate with response in patients with platinum resistant high grade serous ovarian carcinoma in the expansion.
IV. To measure changes in HER2 expression over the course of treatment by IHC and immune multiple reaction monitoring-mass spectrometry (immunoMRM) and correlate with response in patients with platinum resistant high grade serous ovarian carcinoma in dose expansion.
V. To determine biomarkers of response and resistance in tumor specimens and blood specimens, including whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing.
OUTLINE: This is a dose-escalation study of trastuzumab deruxtecan in combination with olaparib followed by a dose-expansion study.
Patients receive trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1 and olaparib orally (PO) twice daily (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, echocardiography (ECHO) or multigated acquisition scan (MUGA), computed tomography (CT), and biopsies throughout the trial.
After completion of study treatment, patients are followed up for 30 days.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2020-07841 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 10355 | OTHER | Dana-Farber - Harvard Cancer Center LAO | View | |
| 10355 | OTHER | CTEP | View | |
| UM1CA186709 | NIH | None | https://reporter.nih.gov/quic… | View |