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

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ClinicalTrials.gov Identifier: NCT03451162
Recruitment Status : Completed
First Posted : March 1, 2018
Last Update Posted : July 14, 2021
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE February 16, 2018
First Posted Date  ICMJE March 1, 2018
Last Update Posted Date July 14, 2021
Actual Study Start Date  ICMJE April 17, 2018
Actual Primary Completion Date June 14, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 23, 2018)
  • Percentage of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: From Day 1 to end of study (up to approximately 45 months) ]
  • Percentage of Participants with DLT [ Time Frame: From Day 1 up to Day 21 ]
  • MTD of DHES0815A [ Time Frame: From Day 1 up to Day 21 ]
  • Recommended Phase 2 Dose (RP2D) of DHES0815A [ Time Frame: From Day 1 up to Day 21 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2018)
  • Concentration of DHES0815A [ Time Frame: Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days) ]
  • Area Under the Concentration-Time Curve (AUC) of DHES0815A [ Time Frame: Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days) ]
  • Maximum Observed blood Concentration (Cmax) of DHES0815A [ Time Frame: Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days) ]
  • Minimum Observed blood Concentration (Cmin) of DHES0815A [ Time Frame: Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days) ]
  • Clearance of DHES0815A [ Time Frame: Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days) ]
  • Volume of Distribution at Steady State (Vss) of DHES0815A [ Time Frame: Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days) ]
  • Percentage 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 complete response (CR) or partial response (PR) (up to approximately 45 months) ]
  • Duration of Response (DoR) Assessed According to RECIST v1.1 [ Time Frame: From the initial CR or PR to the time of disease progression (PD) or death, whichever occurs first (up to approximately 45 months) ]
  • Percentage of Participants with Anti-Drug Antibody (ADA) to DHES0815A [ Time Frame: Pre-dose (0 hours) on Day 1 up to 42 days after last infusion (up to approximately 45 months) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer
Official Title  ICMJE A Phase I, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Escalating Doses of DHES0815A in Patients With HER2-Positive Breast Cancer
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: DHES0815A
DHES0815A will be administered via intravenous (IV) infusion on Day 1 of each 21-day cycle.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: DHES0815A
  • 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.
    Intervention: Drug: DHES0815A
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 21, 2019)
14
Original Estimated Enrollment  ICMJE
 (submitted: February 23, 2018)
55
Actual Study Completion Date  ICMJE June 14, 2021
Actual Primary Completion Date June 14, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 metastases
  • Cardiopulmonary dysfunction, including inadequate left ventricular ejection function at baseline, less than 50% by either echocardiogram or multiple-gated acquisition scan
  • QT interval corrected through use of Fridericia's formula (QTcF) > 470 milliseconds
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03451162
Other Study ID Numbers  ICMJE GO39869
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Genentech, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP