Phase 2
Completed N=40
A Study of Pertuzumab With High-Dose Trastuzumab for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (MBC) With Central Nervous System (CNS) Progression Post-Radiotherapy
Source: ClinicalTrials.gov NCT02536339 ↗Enrolled (actual)
40
Serious AEs
18.0%
Results posted
Mar 2020
Primary outcomePrimary: Percentage of Participants With Objective Response in the CNS, Assessed Using Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) Criteria — 10.8; 0.0; 10.8; 89.2 Percentage of Participants
Summary
This study will examine the safety and efficacy of pertuzumab in combination with high-dose trastuzumab in adult participants with HER2-positive MBC with CNS metastases and disease progression in the brain following radiotherapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Objective Response in the CNS, Assessed Using Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) Criteria |
10.8; 0.0; 10.8; 89.2 | — |
| SECONDARY Median Duration of Response in the CNS, Assessed Using RANO-BM Criteria |
4.60 | — |
| SECONDARY Percentage of Participants With Clinical Benefit (Confirmed CR, PR, or Stable Disease [SD] ≥4 Months) in the CNS, Assessed Using RANO-BM Criteria |
67.6; 0.0; 10.8; 56.8; 32.4 | — |
| SECONDARY Median Duration of Clinical Benefit (Confirmed CR, PR, or SD ≥4 Months) in the CNS, Assessed Using RANO-BM Criteria |
6.64 | — |
| SECONDARY Percentage of Participants With Clinical Benefit (Confirmed CR, PR, or SD ≥6 Months) in the CNS, Assessed Using RANO-BM Criteria |
51.4; 0.0; 10.8; 40.5; 48.6 | — |
| SECONDARY Median Duration of Clinical Benefit (Confirmed CR, PR, or SD ≥6 Months) in the CNS, Assessed Using RANO-BM Criteria |
9.23 | — |
| SECONDARY Progression-Free Survival (CNS), Assessed Using RANO-BM Criteria |
4.63 | — |
| SECONDARY Progression-Free Survival (Systemic), Assessed Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) |
16.26 | — |
| SECONDARY Progression-Free Survival (CNS or Systemic), Assessed Using RANO-BM Criteria and RECIST v1.1 |
4.63 | — |
| SECONDARY Overall Survival |
27.17 | — |
| SECONDARY Number of Deaths by Time (≤30 or >30 Days) From Last Study Drug Administration and by Primary Cause of Death |
20; 1; 19; 16; 1; 3 | — |
| SECONDARY Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) by Highest Grade of Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) |
38; 5; 16; 14; 3; 0 | — |
| SECONDARY Number of Participants With at Least One Treatment-Emergent Serious Adverse Event (SAE) by Highest Grade of Severity, According to NCI-CTCAE v4.0 |
7; 0; 1; 5; 2; 0 | — |
| SECONDARY Number of Participants With at Least One TEAE Leading to Withdrawal of Any Study Drug, Pertuzumab Only, or Both Pertuzumab and Trastuzumab, by Highest Grade of Severity According to NCI-CTCAE v4.0 |
2; 2; 0; 2; 2 | — |
| SECONDARY Number of Participants With at Least One TEAE Leading to Pertuzumab Infusion Delay, Slow Down, or Interruption, by Highest Grade of Severity According to NCI-CTCAE v4.0 |
7; 1; 4; 1; 1; 0 | — |
| SECONDARY Number of Participants With at Least One TEAE Leading to Trastuzumab Dose Modification by Highest Grade of Severity According to NCI-CTCAE v4.0 |
12; 2; 4; 5; 1; 0 | — |
| SECONDARY Percentage of Participants With at Least One TEAE of Special Interest by Highest Grade of Severity, According to NCI-CTCAE v4.0 |
2.6; 2.6 | — |
| SECONDARY Median Left Ventricular Ejection Fraction (LVEF) Values Over Time |
60.00; 60.00; 60.00; 60.00; 60.00; 60.00 | — |
| SECONDARY Number of Participants by Investigator Interpretation of Left Ventricular Ejection Fraction (LVEF) Assessments Over Time |
39; 0; 0; 33; 0; 1 | — |
| SECONDARY Number of Participants With NCI-CTCAE v4.0 Grades 3 and 4 Clinical Laboratory Abnormalities in Hematology Tests Over Time |
3; 0; 1; 0; 2; 0 | — |
| SECONDARY Number of Participants With NCI-CTCAE v4.0 Grades 3 and 4 Clinical Laboratory Abnormalities in Blood Chemistry Tests Over Time |
0; 2; 0; 0; 1; 1 | — |
| SECONDARY Observed Trough Serum Concentrations (Cmin) of Pertuzumab at Specified Timepoints |
43.12; 88.03; 94.46; 101.99 | — |
| SECONDARY Maximum Serum Concentrations (Cmax) of Pertuzumab at Specified Timepoints |
275.94; 225.55 | — |
| SECONDARY Observed Trough Serum Concentrations (Cmin) of Trastuzumab at Specified Timepoints |
57.00; 190.82; 294.50; 306.14 | — |
| SECONDARY Maximum Serum Concentrations (Cmax) of Trastuzumab at Specified Timepoints |
181.43; 394.14 | — |
| SECONDARY Symptom Severity Scale Score Over Time, Assessed by Participant Reporting on the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT) Questionnaire |
1.65; 1.97; 2.24; 2.09; 1.94; 2.78 | — |
| SECONDARY Symptom Interference Scale Score Over Time, Assessed by Participant Reporting on the MDASI-BT Questionnaire |
2.51; 2.23; 2.81; 2.11; 1.76; 3.24 | — |
Eligibility Criteria
Inclusion Criteria
- Pathologically confirmed HER2-positive MBC
- Progression of or new brain metastases after completion of whole-brain radiotherapy or stereotactic radiosurgery
- Completion of whole-brain radiotherapy or stereotactic radiosurgery more than 60 days prior to enrollment
- Stable systemic disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- LVEF at least 50%
- Adequate hematologic, renal, and hepatic function
- Life expectancy more than 12 weeks
Exclusion Criteria
- Progression of systemic disease at Screening
- Leptomeningeal disease
- History of intolerance or hypersensitivity to study drug
- Use of certain investigational therapies within 21 days prior to enrollment
- Current anthracycline use
- Unwillingness to discontinue ado-trastuzumab emtansine or lapatinib use
- Active infection
- Pregnant or lactating women
- Significant history or risk of cardiac disease
- Symptomatic intrinsic lung disease or lung involvement
- History of other malignancy within the last 5 years
Data sourced from ClinicalTrials.gov (NCT02536339). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.