Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer

February 25, 2024 updated by: Genentech, Inc.

A Phase I, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Escalating Doses of DHES0815A in Patients With HER2-Positive Breast Cancer

This first-in-human, Phase 1, open-label, multicenter, dose-escalation study will evaluate the safety, tolerability, and PK of DHES0815A as a single agent in participants with advanced and/or metastatic HER2-positive breast cancer for whom established treatment has proven ineffective or intolerable or is unavailable. The study may include a dose-expansion cohort (based on an ongoing assessment of the totality of data obtained in this study) to further assess safety, tolerability, PK, and preliminary anti-tumor activity.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • New York
      • New York, New York, United States, 11101
        • Memorial Sloan Kettering Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Measurable disease by RECIST v1.1 with at least one measurable target lesion
  • Locally advanced or metastatic HER2-positive breast cancer that has relapsed or is refractory to established therapies
  • Adequate hematologic and end-organ function
  • For dose-expansion cohort only: no more than two prior systemic chemotherapy-containing regimens in the advanced/metastatic setting (excluding trastuzumab emtansine, which is considered a targeted cytotoxic agent)

Key Exclusion Criteria:

  • Treatment with chemotherapy, hormonal therapy (except hormone replacement therapy, oral contraceptives), immunotherapy, biologic therapy, radiation therapy (except palliative radiation to bony metastases), or herbal therapy as cancer therapy within 4 weeks prior to initiation of DHES0815A
  • History of exposure to the protocol specified doses of anthracyclines
  • Pregnancy, lactation, or breastfeeding
  • Major surgical procedure within 4 weeks prior to Day 1
  • Evidence of a significant uncontrolled concomitant disease of the nervous system, pulmonary, autoimmune, renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture
  • Known active bacterial, viral, fungal, mycobacterial, or other infection
  • Clinically significant history of liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Untreated or active central nervous system (CNS) metastases
  • Cardiopulmonary dysfunction, including inadequate left ventricular ejection function at baseline, less than 50% by either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
  • QT interval corrected through use of Fridericia's formula (QTcF) > 470 milliseconds (ms)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose Escalation Cohort: DHES0815A
Participants will receive DHES0815A in escalating doses in the dose-escalation cohort of the study. Participants will receive additional infusions of DHES0815A on Day 1 of subsequent cycles provided that they meet the protocol specified criteria for acceptable toxicity and ongoing clinical benefit.
Drug: DHES0815A
DHES0815A will be administered via intravenous (IV) infusion on Day 1 of each 21-day cycle.
Experimental: Dose Expansion Cohort: DHES0815A
Participants will be treated at or below the Maximum Tolerated Dose (MTD) of DHES0815A (based on the review of the totality of the data) to obtain additional safety, tolerability, PK, and anti-tumor activity data.
Drug: DHES0815A
DHES0815A will be administered via intravenous (IV) infusion on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) With Severity Determined as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Time Frame: From Day 1 to end of study (up to approximately 39 months)
AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. SAE is any AE that is fatal, is life threatening, requires or prolongs inpatient hospitalization, results in persistent/significant disability/incapacity and is congenital anomaly/birth defect. Severity of AEs were graded per NCI CTCAE v4.0. Grade 1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2: Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3: Severe/medically significant, but not immediately life-threatening: hospitalization/prolongation of hospitalization indicated; disabling/limiting self-care activities of daily living; Grade 4: Life-threatening consequences/urgent intervention indicated; Grade 5: Death related to AE.
From Day 1 to end of study (up to approximately 39 months)
Number of Participants With Dose-limiting Toxicity (DLT)
Time Frame: From Day 1 up to Day 21
DLT=any one events occurring during DLT assessment window: ≥15% decrease from baseline in left ventricular ejection fraction (LVEF)/≥10% decrease to <50% LVEF; Grade ≥ 3 non-hematologic toxicity; Grade ≥4 neutropenia (absolute neutrophil count <500 cells/microliters [μL]) lasting <7 days; Grade ≥3 febrile neutropenia; Grade ≥4 anemia; Grade ≥4 thrombocytopenia; Grade 3 thrombocytopenia associated with clinically significant bleeding; Any increase in hepatic transaminase (ALT or AST) >3*baseline in combination with either an increase in direct bilirubin >2*upper limit of normal/clinical jaundice, in absence of cholestasis/other contributory factors. NCI CTCAE v4.0. was used to grade these events.Grade1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; Grade2: Moderate; minimal, local/non-invasive intervention indicated;Grade3: Severe/medically significant, but not immediately life-threatening;Grade4: Life-threatening consequences/urgent intervention indicated.
From Day 1 up to Day 21
Duration of Treatment
Time Frame: From Day 1 up to last dose of study drug (up to approximately 39 months)
Treatment duration was calculated from the first dose of study drug to the last dose of study drug administration.
From Day 1 up to last dose of study drug (up to approximately 39 months)
Total Cumulative Dose
Time Frame: From Day 1 up to last dose of study drug (up to approximately 39 months)
From Day 1 up to last dose of study drug (up to approximately 39 months)
Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan
Time Frame: Baseline, end of Cycle 1, Days 15-21 of Cycles 2, 4, and 6, and every four cycles thereafter up to the study discontinuation visit (up to approximately 39 months)
LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heartbeat and is a measure of cardiac output for the heart. Baseline LVEF value and the change from baseline to the worst value in LVEF measurement were reported. LVEF was measured by ECHO or MUGA scan.
Baseline, end of Cycle 1, Days 15-21 of Cycles 2, 4, and 6, and every four cycles thereafter up to the study discontinuation visit (up to approximately 39 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Concentration of DHES0815A Total Antibody
Time Frame: Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)
DHES0815A total antibody is one of three key pharmacokinetic analytes of DHES0815A.
Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)
Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)
Time Frame: Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)
Conjugated PDB-MA is one of three key pharmacokinetic analytes of DHES0815A.
Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)
Concentration of Plasma Unconjugated PDB-MA
Time Frame: Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)
Plasma Unconjugated PDB-MA is one of three key pharmacokinetic analytes of DHES0815A.
Pre-dose and 30 minutes (min) post-dose on Day 1 Cycles 1-4; 4 hour (h) post-dose on Day 1 Cycle1; post-dose on Days 2, 3, 11, 17 Cycle 1; post-dose on Days 8 and 15 Cycles 1-4; study discontinuation visit (up to approx. 39 months) (Cycle length=21 days)
Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time Frame: From start of treatment until confirmation of CR or PR (up to approximately 39 months)
Objective response was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR, defined as disappearance of all target lesions. PR, defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR.
From start of treatment until confirmation of CR or PR (up to approximately 39 months)
Duration of Response (DoR) Assessed According to RECIST v1.1
Time Frame: From the initial CR or PR to the time of PD or death, whichever occurs first (up to approximately 39 months)
DOR was defined as the time from the first occurrence of a documented objective response to disease progression (PD) or death from any cause, whichever occurred first, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).
From the initial CR or PR to the time of PD or death, whichever occurs first (up to approximately 39 months)
Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A
Time Frame: Pre-dose on Day 1 of Cycles 1-4 and 42 days after last infusion (up to approximately 39 months)
Number of participants with treatment induced and treatment-enhanced ADA are reported here. Participants were considered to have treatment-induced ADA responses if they were ADA negative at baseline and developed an ADA response following DHES0815A administration. Participants were considered to have treatment-enhanced ADA if they were ADA positive at baseline and the titer of one or more postbaseline samples is at least 4-fold greater than baseline titer (i.e., ≥ 0.60 titer units) following study drug administration.
Pre-dose on Day 1 of Cycles 1-4 and 42 days after last infusion (up to approximately 39 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Genentech, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 17, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 16, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 16, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 16, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 1, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 5, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GO39869

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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