Abstract CT179: Safety and effectiveness of plasmapheresis-based elimination of soluble TNFα receptors combined with chemotherapy in advanced, chemorefractory triple-negative breast cancer patients - a phase I/II study (CP7-005)
Authors: Wysocki Piotr Jan , Ostrowski Adam , Segal Robert , Manax Victoria , Potocki Pawel , Konopka Kamil , Kwinta Lukasz , Fraczek Paulina , Lubas Maciej , Lobacz Mateusz , Florin Lawrence 
Published: June 2022

Abstract
Introduction: Tumor necrosis factor-alpha (TNFα) is a pleiotropic cytokine with known antitumor activity, produced mainly by activated immune cells. Cancer cells neutralize TNFα by shedding soluble TNF receptors 1&2 (sTNF-Rs), which act as TNFα-binding decoys, promoting cancer cell proliferation, survival, and chemoresistance. Immunopheresis® employs therapeutic apheresis with the selective immunoadsorption LW-02 column (LW-02) for treating solid malignancies. LW-02-based Immunopheresis (granted FDA Breakthrough Device Designation and a CE Mark for mTNBC) selectively removes sTNF-Rs from plasma, permitting TNFα to bind to membrane-bound TNF-Rs, activating intracellular death pathways, and also modulate T-cell-mediated immune activity. Part A data of our phase I/II clinical trial in metastatic, chemorefractory, triple-negative breast cancer (mTNBC) patients (NCT04004910) confirmed that LW-02-based Immunopheresis monotherapy is safe and well-tolerated, with signs of disease stabilization (SD) in patients treated &gt;4 weeks. Here we present interim data on the safety and preliminary efficacy of LW-02 Immunopheresis combined with chemotherapy.
Methods: LW-02 Immunopheresis (3x/week for 16 weeks) is combined with a weekly paclitaxel (80 mg/m2)+carboplatin (AUC 2) regimen in patients with mTNBC; treatment is continued past 16 weeks in clinical and/or objective responders. Primary endpoints are safety and tolerability. Secondary endpoints assessed in patients treated &gt;4 weeks include overall survival, tumor response according to RECIST, rate of CNS progression and quality-of-life.
Results: Of 11 patients enrolled in Part B of the study, 7 patients were treated for &gt;4 weeks. The ORR was 18% (1CR, 1PR) with one additional patient experiencing SD; the ORR and CBR in patients treated &gt;4 weeks were 29% and 43%, respectively. The median OS, to date, is 18.6 weeks and 26.7 weeks in the group treated &gt;4 weeks. The rate of CNS progression (new or preexisting lesions) appears lower than expected. The most common adverse events (AEs) were chemotherapy-induced myelotoxicity (anemia, neutropenia, thrombocytopenia) and transient electrolyte abnormalities. Thirty-one serious AEs (SAEs) were reported for all 11 patients, 15 (48.4%) were transfusion requiring anemias. Of the SAEs, 3 (9.6%) were judged to have a potential causal relationship to LW-02 column Immunopheresis.
Conclusion: LW-02-based Immunopheresis combined with weekly chemotherapy is generally safe, well-tolerated and highly effective in specific sTNFR subtraction on a longer-term basis, with promising signals of clinical benefit in heavily pretreated mTNBC patients (median 3.3 [2-5] prior lines of systemic therapy). Further clinical evaluation of the antitumor activity of LW-02-based immunopheresis combined with low-dose chemotherapy is ongoing with a focus on quality-of-life and prevention of CNS disease progression, the latter especially important in chemorefractory mTNBC, given the high prevalence of CNS involvement.
Citation Format: Piotr Jan Wysocki, Adam Ostrowski, Robert Segal, Victoria Manax, Pawel Potocki, Kamil Konopka, Lukasz Kwinta, Paulina Fraczek, Maciej Lubas, Mateusz Lobacz, Lawrence Florin. Safety and effectiveness of plasmapheresis-based elimination of soluble TNFα receptors combined with chemotherapy in advanced, chemorefractory triple-negative breast cancer patients - a phase I/II study (CP7-005) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT179.