Clinical Trials /

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

NCT03451162

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety, Tolerability, and Pharmacokinetic (PK) Study of DHES0815A in Participants With Human Epidermal Growth Factor Receptor (HER)2-Positive Breast Cancer
  • Official Title: A Phase I, Open-Label Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Escalating Doses of DHES0815A in Patients With HER2-Positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: GO39869
  • NCT ID: NCT03451162

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
DHES0815ADose Escalation Cohort: DHES0815A

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Cohort: DHES0815AExperimentalParticipants 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.
  • DHES0815A
Dose Expansion Cohort: DHES0815AExperimentalParticipants 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.
  • DHES0815A

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events (AEs) and Serious AEs
Time Frame:From Day 1 to end of study (up to approximately 45 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

March 16, 2018