Phase 1b Study of Pegylated Liposomal Doxorubicin and Pembrolizumab in Endocrine-resistant Breast Cancer

Summary

Very few patients with endocrine-resistant, hormone-receptor positive metastatic breast cancer respond to single agent immunotherapy. Responses to chemotherapy are usually of short duration. Combining immunotherapy with chemotherapy that has minimal immunosuppressive effect, it may be possible to achieve higher response rates while keeping the immune-associated pattern of long durations of response. This will be a single-center phase 1b study to evaluate the tumor response and appropriate dose of a chemo-immunotherapy regime consisting of treatment with pegylated liposomal doxorubicin (PLD) and pembrolizumab-based in endocrine-resistant breast cancer (ERBC) patients. Up to 15 female patients, ages 18 and above, with pathological diagnosis of breast cancer, estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2-) negative subtype, stage III non-operable, or stage IV disease, who have received at least two lines of hormonal therapy, one of which included aromatase inhibitors will be eligible for enrollment to this single arm study.

Timeline

Start

2019-04-18

Primary completion

2021-04-15

Completion

2021-06-15

Publications

• Results O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. doi: 10.1093/annonc/mdh097.
• Results Tahover E, Patil YP, Gabizon AA. Emerging delivery systems to reduce doxorubicin cardiotoxicity and improve therapeutic index: focus on liposomes. Anticancer Drugs. 2015 Mar;26(3):241-58. doi: 10.1097/CAD.0000000000000182.
• Results Rios-Doria J, Durham N, Wetzel L, Rothstein R, Chesebrough J, Holoweckyj N, Zhao W, Leow CC, Hollingsworth R. Doxil synergizes with cancer immunotherapies to enhance antitumor responses in syngeneic mouse models. Neoplasia. 2015 Aug;17(8):661-70. doi: 10.1016/j.neo.2015.08.004.
• Results Gabizon AA, Patil Y, La-Beck NM. New insights and evolving role of pegylated liposomal doxorubicin in cancer therapy. Drug Resist Updat. 2016 Nov;29:90-106. doi: 10.1016/j.drup.2016.10.003. Epub 2016 Oct 29.

Drugs

Indications