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Study withdrawn due to change in treatment landscape for HER2+ metastatic breast cancer.
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| Seagen Inc. | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tucatinib + Pembrolizumab + Trastuzumab | Experimental | Patients will receive a combination therapy of tucatinib with pembrolizumab and trastuzumab during the treatment period until progression, treatment intolerance, or patient withdrawal from study. Tucatinib and pembrolizumab are administered as experimental use while trastuzumab is administered per standard use. Patients are expected to be on treatment for at least 12 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tucatinib | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 24-week CNS disease control rate (DCR) | 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. | 24 weeks |
| Recommended dose of tucatinib in combination with pembrolizumab and trastuzumab | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| CNS objective response rate (ORR) | Proportion of participants with confirmed CR or PR per RANO-BM Criteria | From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years. |
| Systemic ORR |
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Inclusion Criteria:
Exclusion Criteria:
Complete inclusion/exclusion criteria are detailed in the protocol.
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| Name | Affiliation | Role |
|---|---|---|
| Reva Basho, MD | Cedars-Sinai Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States |
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| Pembrolizumab | Drug | 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. |
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| Trastuzumab | Drug | 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. |
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Proportion of participants with confirmed CR or PR per RECIST v.1.1
| From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years. |
| Progression-free survival (PFS) | 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. | From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years. |
| Overall Survival (OS) | 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. | From baseline until death or 3 years, whichever occurs first. |
| Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration | Number of adverse events as assessed per CTCAE v.5. | From first dose of study treatment until 30 days after the last dose of study treatment. |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D001932 | Brain Neoplasms |
| D002493 | Central Nervous System Diseases |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D001927 | Brain Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000705452 | tucatinib |
| C582435 | pembrolizumab |
| D000068878 | Trastuzumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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