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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03451162
• Collaborator: (none)
• Enrollment: 14
• Locations: 5
• Arms: 2
• Actual Duration (Months): 39
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: DHES0815A	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 17, 2018
• Actual Primary Completion Date: Jul 16, 2021
• Actual Study Completion Date: Jul 16, 2021

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants with Adverse Events (AEs) and Serious AEs [From Day 1 to end of study (up to approximately 45 months)]

2. Percentage of Participants with DLT [From Day 1 up to Day 21]

3. MTD of DHES0815A [From Day 1 up to Day 21]

4. Recommended Phase 2 Dose (RP2D) of DHES0815A [From Day 1 up to Day 21]

Secondary Outcome Measures

1. Concentration of DHES0815A [Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)]

2. Area Under the Concentration-Time Curve (AUC) of DHES0815A [Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)]

3. Maximum Observed blood Concentration (Cmax) of DHES0815A [Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)]

4. Minimum Observed blood Concentration (Cmin) of DHES0815A [Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)]

5. Clearance of DHES0815A [Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)]

6. Volume of Distribution at Steady State (Vss) of DHES0815A [Cycle 1 Day 1 up to 42 days after last dose (up to approximately 45 months) (Cycle length = 21 days)]

7. Percentage of Participants with Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [From start of treatment until confirmation of complete response (CR) or partial response (PR) (up to approximately 45 months)]

8. Duration of Response (DoR) Assessed According to RECIST v1.1 [From the initial CR or PR to the time of disease progression (PD) or death, whichever occurs first (up to approximately 45 months)]

9. Percentage of Participants with Anti-Drug Antibody (ADA) to DHES0815A [Pre-dose (0 hours) on Day 1 up to 42 days after last infusion (up to approximately 45 months)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Cancer Center	New Haven	Connecticut	United States	06520
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
5	Asan Medical Center	Seoul		Korea, Republic of	05505

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT03451162
• Other Study ID Numbers: GO39869
• First Posted: Mar 1, 2018
• Last Update Posted: Jan 21, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

No Results Posted as of Jan 21, 2022