T-DM1 With or Without Abemaciclib for the Treatment of HER2-Positive Metastatic Breast Cancer

Summary

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PRIMARY OBJECTIVES: I. To assess whether progression-free survival (PFS) is improved with the addition of abemaciclib to trastuzumab emtansine (T-DM1) for patients with estrogen receptor positive (ER+)HER2-positive advanced or metastatic breast cancer who progressed on treatment with a taxane, trast...

PRIMARY OBJECTIVES: I. To assess whether progression-free survival (PFS) is improved with the addition of abemaciclib to trastuzumab emtansine (T-DM1) for patients with estrogen receptor positive (ER+)HER2-positive advanced or metastatic breast cancer who progressed on treatment with a taxane, trastuzumab and pertuzumab (Cohort 1). II. To assess whether progression-free survival (PFS) is improved with the addition of abemaciclib to T-DM1 for patients with estrogen receptor negative (ER-) HER2-positive advanced or metastatic breast cancer who progressed on treatment with a taxane, trastuzumab and pertuzumab (Cohort 2). SECONDARY OBJECTIVES: I. To assess the safety and tolerability of each treatment regimen. II. To assess overall survival (OS) and objective response rate (ORR) of each treatment regimen. CORRELATIVE RESEARCH OBJECTIVES: I. To assess whether the presence of vimentin expression or the level of tumor infiltrating lymphocytes (TILs) in the baseline tumor specimen is associated with an increased likelihood of longer PFS in the abemaciclib arms compared to the non-abemaciclib arms (regardless of ER status). II. To assess both the baseline prognostic effects of circulating tumor cell (CTC) levels, ER expression in CTCs, HER2 expression in CTCs, serum TK1 levels, circulating tumor-derived deoxyribonucleic acid (ctDNA), ESR1, or PIK3CA mutations and whether a reduction in these levels after 2 cycles of treatment is associated with an increased likelihood of longer PFS overall and separately in the treatment arms. III. To assess whether polymorphisms in FCgamma receptors (FCGR2A and FCGR3A) are associated with inferior PFS. IV. To describe alterations seen in the peripheral blood immune system architecture after 2 cycles of treatment. V. To assess whether peripheral blood immune markers at baseline are prognostic and whether change in peripheral blood immune markers after 2 cycles of treatment are associated with PFS. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive T-DM1 intravenously (IV) over 90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive T-DM1 IV over 90 minutes on day 1 and abemaciclib orally (PO) twice daily (BID) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months for up to 5 years.

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