Clinical trial NCT03451162: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2018-03-01
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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 (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)

Primary outcomes:
measure: 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
timeFrame: From Day 1 to end of study (up to approximately 39 months)
measure: Number of Participants With Dose-limiting Toxicity (DLT)
timeFrame: From Day 1 up to Day 21
measure: Duration of Treatment
timeFrame: From Day 1 up to last dose of study drug (up to approximately 39 months)
measure: Total Cumulative Dose
timeFrame: From Day 1 up to last dose of study drug (up to approximately 39 months)
measure: Change From Baseline in LVEF as Assessed by Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan
timeFrame: 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 outcomes:
measure: Concentration of DHES0815A Total Antibody
timeFrame: 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)
measure: Concentration of Plasma Conjugated Pyrrolo [2,1-c] [1,4] Benzodiazepine Monoamide (PDB-MA)
timeFrame: 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)
measure: Concentration of Plasma Unconjugated PDB-MA
timeFrame: 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)
measure: Number of Participants With Objective Response Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: From start of treatment until confirmation of CR or PR (up to approximately 39 months)
measure: Duration of Response (DoR) Assessed According to RECIST v1.1
timeFrame: From the initial CR or PR to the time of PD or death, whichever occurs first (up to approximately 39 months)
measure: Number of Participants With Anti-Drug Antibody (ADA) to DHES0815A
timeFrame: Pre-dose on Day 1 of Cycles 1-4 and 42 days after last infusion (up to approximately 39 months)
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: