Avelumab With Binimetinib, Sacituzumab Govitecan, or Liposomal Doxorubicin in Treating Stage IV or Unresectable, Recurrent Triple Negative Breast Cancer
brief summary
This phase II trial studies how well the combination of avelumab with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan works in treating patients with triple negative breast cancer that is stage IV or is not able to be removed by surgery (unresectable) and has come back (recurrent). Immunotherapy with checkpoint inhibitors like avelumab require activation of the patient's immune system. This trial includes a two week induction or lead-in of medications that can stimulate the immune system. It is our hope that this induction will improve the response to immunotherapy with avelumab. One treatment, sacituzumab Govitecan, is a monoclonal antibody called sacituzumab linked to a chemotherapy drug called SN-38. Sacituzumab govitecan is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as Tumor-associated calcium signal transducer 2 (TROP2) receptors, and delivers SN-38 to kill them. Another treatment, liposomal doxorubicin, is a form of the anticancer drug doxorubicin that is contained in very tiny, fat-like particles. It may have fewer side effects and work better than doxorubicin, and may enhance factors associated with immune response. The third medication is called binimetinib, which may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may help activate the immune system. It is not yet known whether giving avelumab in combination with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan will work better in treating patients with triple negative breast cancer.
detailed description
OUTLINE: Patients are randomized to 1 of 3 active arms. The three previous study arms are closed to further accrual.
ARM A: Patients receive binimetinib orally (PO) twice daily (BID) for a lead-in period of 15 days in the absence of disease progression or unacceptable toxicity. Patients then receive binimetinib PO BID on days 1-28, avelumab intravenously (IV) over 60 minutes on days 1 and 15, and liposomal doxorubicin IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive sacituzumab govitecan IV on days -15 for a lead-in period in the absence of disease progression or unacceptable toxicity. Patients then receive sacituzumab govitecan day 8 and day 15 of Cycle (C) 1; day 1, 8, and 21 of C2; day 1, 15 and 21 of C3; day 8 and 15 of C4, and the schedule continues with two weeks on, one week off for 21-day cycles which repeat in the absence of disease progression or unacceptable toxicity. Participants also receive avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM C: Patients receive liposomal doxorubicin IV over 60 minutes on day -15 for a lead-in period of 15 days in the absence of disease progression or unacceptable toxicity. Patients then receive liposomal doxorubicin IV over 60 minutes on day 15 and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then every 6 months for a minimum of 1 year. Participants will be followed every 3 months after experiencing disease progression to assess for survival/anti-cancer therapy status until death or 1 year after Cycle 1 Day 1.
PRIMARY OBJECTIVE:
I. Anti-tumor effect of avelumab in combination with different therapeutic agents explored in the sub-protocols of the trial.
SECONDARY OBJECTIVES:
I. Additional anti-tumor effects.
II. Safety and tolerability of avelumab in combination with different therapeutic agents explored in the sub-protocols of the trial.
III. Patient reported outcomes (PRO) between baseline and cycle 3 day 1 across arms.
official title
Innovative Combination Immunotherapy for Metastatic Triple Negative Breast Cancer (TNBC): A Multicenter, Multi-Arm Translational Breast Cancer Research Consortium Study