TABLE 2.
Selected ongoing clinical trials of targeted therapy and immunotherapy in patients with BCBM
| Treatment | NCT identifier | Title | Phase | Number of patients | Primary point |
|---|---|---|---|---|---|
| HER2 targeted drug | NCT02614794 | Phase 2 Randomized, Double‐Blinded, Controlled Study of Tucatinib vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma | II | 612 | PFS |
| NCT03975647 | Randomized, Double‐blind, Phase 3 Study of Tucatinib or Placebo in Combination With Ado‐trastuzumab Emtansine (T‐DM1) for Subjects With Unresectable Locally advanced or Metastatic HER2+ Breast Cancer (HER2CLIMB‐02) | III | 460 | PFS | |
| NCT03933982 | Pyrotinib Plus Vinorelbine in Patients With Brain Metastases From HER2‐positive Metastatic Breast Cancer: a Prospective, Single‐arm, Open‐label Study | II | 30 | CNS ORR | |
| NCT03691051 | Pyrotinib Plus Capecitabine in Patients With Brain Metastases From HER2‐positive Metastatic Breast Cancer: a Single‐arm, Open‐label, Ahead Study | II | 78 | CNS ORR | |
| NCT04303988 | A Prospective, Single‐arm, Single‐center, Multi‐cohort Phase II Clinical Study of HER2‐positive and Triple‐negative BCBM | II | 59 | CNS ORR | |
| NCT01494662 | A Phase II Trial of HKI‐272 (Neratinib), Neratinib, and Capecitabine, and Ado‐Trastuzumab Emtansine for Patients With Human Epidermal Growth Factor Receptor 2 (HER2)‐Positive Breast Cancer and Brain Metastases | II | 168 | ORR | |
| NCT02536339 | An Open‐Label, Single‐Arm, Phase II Study of Pertuzumab With High‐Dose Trastuzumab for the Treatment of Central Nervous System Progression Post‐Radiotherapy in Patients With HER2‐Positive Metastatic Breast Cancer (PATRICIA) | II | 40 | CNS ORR | |
| NCT03417544 | A Phase II Study of Atezolizumab in Combination With Pertuzumab Plus High‐dose Trastuzumab for the Treatment of Central Nervous System Metastases in Patients With Her2‐positive Breast Cancer | II | 33 | CNS ORR | |
| NCT01622868 | Phase II Randomized Study of Whole Brain Radiotherapy/Stereotactic Radiosurgery in Combination With Concurrent Lapatinib in Patients With Brain Metastasis From HER2‐Positive Breast Cancer ‐ A Collaborative Study of NRG Oncology and KROG | II | 143 | CR Rate in the Brain at 12 Weeks after RT | |
| NCT03190967 | Phase I/II Study of T‐DM1 Alone Versus T‐DM1 and Metronomic Temozolomide in Secondary Prevention of HER2‐Positive Breast Cancer Brain Metastases Following Stereotactic Radiosurgery | I/II | 125 | Maximum tolerated dose of TMZ; Median time to progression | |
| NCT03054363 | Phase IB/II Open‐label Single‐Arm Study to Evaluate Safety and Efficacy of Tucatinib in Combination With Palbociclib and Letrozole in Subjects With Hormone Receptor‐Positive and HER2‐positive Metastatic Breast Cancer | I/II | 42 | Phase I: safety and tolerability Phase II: PFS | |
| PI3K inhibitor | NCT03765983 | Phase II Trial of GDC‐0084 in Combination With Trastuzumab for Patients With HER2‐Positive BCBM | II | 47 | CNS ORR |
| NCT02000882 | Phase II Multicenter Single‐arm Study of BKM120 Plus Capecitabine for Breast Cancer Patients With Brain Metastases | II | 10 | CBR | |
| mTOR inhibitor | NCT01305941 | A Phase II Study Evaluating The Efficacy And Tolerability Of Everolimus (RAD001) In Combination With Trastuzumab And Vinorelbine In The Treatment Of Progressive HER2‐Positive BCBM | II | 32 | CNS ORR |
| NCT01283789 | Phase II Trial of Lapatinib and RAD‐001 for HER2 Positive Metastatic Breast Cancer | II | 23 | Efficacy | |
| NCT01783756 | Phase 1b/2 Single‐arm Trial Evaluating the Combination of Lapatinib, Everolimus, and Capecitabine for the Treatment of Patients With HER2‐positive Metastatic Breast Cancer With CNS Progression After Trastuzumab | I/II | 9 | CNS ORR | |
| CDK4/6 inhibitor | NCT02896335 | A Phase 2 Study of Palbociclib in Progressive Brain Metastases Harboring Alterations in the CDK Pathway | II | 30 | CBR |
| NCT02308020 | A Phase 2 Study of Abemaciclib in Patients With Brain Metastases Secondary to Hormone Receptor‐Positive Breast Cancer, Non‐small Cell Lung Cancer, or Melanoma | II | 162 | CNS ORR | |
| NCT04334330 | Palbociclib, Trastuzumab, Lapatinib and Fulvestrant Treatment in Patients With Brain Metastasis From ER Positive, HER‐2 Positive Breast Cancer: A Multi‐center, Prospective Study in China | II | 48 | CNS ORR | |
| PARP inhibitor | NCT02595905 | Phase II Randomized Placebo‐Controlled Trial of Cisplatin With or Without ABT‐888 (Veliparib) in Metastatic Triple‐Negative Breast Cancer and/or BRCA Mutation‐Associated Breast Cancer, With, or Without Brain Metastases | II | 333 | PFS |
| NCT01173497 | A Phase II Study of the PARP Inhibitor, INIPARIB (BSI‐201), in Combination With Chemotherapy to Treat Triple‐Negative BCBM | II | 44 | Efficacy | |
| NCT04508803 | Combination of HX008 And Niraparib in germ‐line‐mutated metastatic breast cancer: a multi‐center Phase II study | II | 50 | ORR | |
| Immunotherapy | NCT04303988 | A Prospective, Single‐arm, Single‐center, Multi‐cohort Phase II Clinical Study of HER2‐positive and Triple‐negative BCBM | II | 59 | CNS ORR |
| NCT03449238 | Pembrolizumab And SRS Of Selected Brain Metastases In Breast Cancer Patients | I/II | 41 | Tumor response for non‐irradiated brain lesions at 8 weeks | |
| NCT03483012 | A Phase II Study of Atezolizumab in Combination With SRS for Patients With Triple‐negative Breast Cancer and Brain Metastasis | II | 45 | PFS | |
| Other therapies | NCT03696030 | A Phase 1 Cellular Immunotherapy Study of Intraventricularly Administered Autologous HER2‐Targeted Chimeric Antigen Receptor (HER2‐CAR) T Cells in Patients With Brain and/or Leptomeningeal Metastases From HER2 Positive Cancers | I | 39 | Incidence of dose‐limiting toxicities; treatment‐related adverse events |
| NCT04158947 | A Randomized Study of HER2+ Breast Cancer Patients With Active Refractory Brain Metastases Treated With Afatinib in Combination With T‐DM1 vs. T‐DM1 Alone | I/II | 130 | Safety and tolerability | |
| NCT03613181 | A Randomized Open‐Label, Multi‐Center Pivotal Study of ANG1005 Compared With Physician's Best Choice in HER2‐Negative Breast Cancer Patients With Newly Diagnosed Leptomeningeal Carcinomatosis and Previously Treated Brain Metastases (ANGLeD) | III | 150 | OS | |
| NCT02581839 | Treatment of Brain Metastases From Breast Cancer With Eribulin Mesylate | II | 9 | CNS PFS | |
| NCT02260531 | A Phase II Study of Cabozantinib Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases | II | 36 | CNS ORR |
Abbreviation: BCBM, breast cancer brain metastases; CBR, clinical benefit rate; CNS, central nervous system; ORR, objective response rate; OS, overall survival; PFS, progression‐free survival; RT, radiation therapy; SRS, stereotactic radiosurgery; TMZ, temozolomide; T‐DM1, trastuzumab Emtansine.