Brain Metastases, Breast Cancer, CNS Disease, HER2-positive Breast Cancer
Conditions
Keywords
tucatinib, pembrolizumab, trastuzumab
Brief summary
This is a single arm, open label trial to assess the safety and efficacy of tucatinib in combination with pembrolizumab and trastuzumab for the treatment of HER2+ breast cancer brain metastases (BCBM). A total of 33 patients with untreated or previously treated and progressing HER2+ BCBM not requiring urgent central nervous system (CNS)-directed therapy will be enrolled. The study will determine the recommended dose of tucatinib in this combination and assess the efficacy of this combination in controlling CNS disease in patients with HER2+ BCBM.
Interventions
DRUGTucatinib
Initial dosage of trial treatment for tucatinib will be given as 300 mg (dispensed as 2 x 150 mg tablets) orally twice a day for Days 1 - 21 of each 3-week cycle during the treatment period.
DRUGPembrolizumab
Initial dosage of trial treatment for pembrolizumab will be given as 200 mg by intravenous infusion every 3 weeks on Day 1 of each 3-week cycle during the treatment period. Pembrolizumab will be administered for a maximum of 35 doses.
DRUGTrastuzumab
Initial dosage of trial treatment for trastuzumab will be given as 8 mg/kg by intravenous (IV) infusion once on Day 1 of Cycle 1, and 6 mg/kg by IV every 3 weeks on Day 1 of each 3-week cycle starting on Cycle 2 during the treatment period.
Sponsors
Merck Sharp & Dohme LLC
Seagen Inc.
Reva Basho
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. ECOG performance status of 0-2. 3. HER2+ (as defined by ASCO/CAP clinical practice guideline) metastatic breast cancer. 4. Untreated or previously treated and progressing CNS disease. 5. Measurable CNS metastases. 6. Must be able to undergo MRI of the brain. 7. Adequate organ function.
Exclusion criteria
1. Any indication for immediate CNS-directed therapy. 2. History of generalized or complex partial seizures. 3. Any other manifestation of neurologic progression that in the opinion of the treating physician is due to brain metastases. 4. Leptomeningeal disease. 5. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor. 6. Prior therapy with tucatinib. 7. Active autoimmune disease that has required systemic treatment in excess of prednisone 10mg daily or equivalent in the past 2 years. Complete inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-week CNS disease control rate (DCR) | 24 weeks | Percentage of patients who experience objective tumor response \[ partial response (PR) or complete response (CR) \] or stable disease as assessed by investigator per RANO-BM reads on protocol-specified MRIs of the brain. |
| Recommended dose of tucatinib in combination with pembrolizumab and trastuzumab | 24 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CNS objective response rate (ORR) | From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years. | Proportion of participants with confirmed CR or PR per RANO-BM Criteria |
| Overall Survival (OS) | From baseline until death or 3 years, whichever occurs first. | From date of registration to date of death due to any cause. Patient's last known to be alive are censored at date of last contact. |
| Progression-free survival (PFS) | From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years. | From date of registration to date of first documentation of true progression or symptomatic deterioration (as defined above), or death due to any cause. Patients last known to be alive and progression free are censored at date of last assessment. PFS will be assessed in the CNS and systemically. |
| Systemic ORR | From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years. | Proportion of participants with confirmed CR or PR per RECIST v.1.1 |
| Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration | From first dose of study treatment until 30 days after the last dose of study treatment. | Number of adverse events as assessed per CTCAE v.5. |
Countries
United States
Outcome results
None listed