Preliminary data on antitumor activity of extracorporeal subtraction of soluble TNFRs to unleash the activity of endogenous TNFα combined with chemotherapy in treatment-refractory, advanced, triple-negative breast cancer patients.

e13052 Background: 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 (sTNFRs), which act as TNFα-binding decoys. In addition, sTNFRs can directly promote proliferation, survival, and chemoresistance of cancer cells by binding to membrane-bound TNFα and initiating retrograde signaling. Therefore, the reduction of systemic and intratumoral concentrations of sTNFRs represents a novel and unique strategy to reinvent the anticancer use of TNFα. Methods: In this clinical trial (CP7-005; NCT04004910) we evaluated extracorporeal Immunopheresis (subtractive apheresis) with the novel LW-02 immunoadsorption column in advanced chemo-refractory metastatic triple-negative breast cancer (mTNBC). The LW-02 column, which utilizes a proprietary, recombinant single-chain TNFα as the sTNFR-scavenger ligand has received FDA breakthrough designation for cancer treatment. Here we present data on the second cohort of mTNBC patients treated with LW-02 combined with weekly chemotherapy; Cohort 1 (n=10) evaluated Immunopheresis as monotherapy only. In Cohort 2, patients are treated with LW-02 immunopheresis only in week 1 (3 treatments involving processing of 2 plasma volumes (2PV)). From week 2, paclitaxel [60 mg/m2]+carboplatin[AUC2] combination is administered once weekly along with LW-02 immunopheresis (2PV 3x/week). Results: To date, 7 mTNBC patients who failed ≥2 lines of chemotherapy (median=3; 2-5) in the advanced setting have been enrolled. The combination of LW-02 column immunopheresis and chemotherapy resulted in a 29% ORR (1CR, 1PR). In 5 patients who completed at least 4 weeks of treatment, the ORR was 40%. Median OS in the whole population as of this report is 13.3 weeks, and 18.4 weeks in the patients treated for >4 weeks. Treatment-related AEs occurred in most patients; however, most being attributed to chemotherapy - CTCAE G3-4 in 71% (anemia – 71%, neutropenia 29%, thrombocytopenia 29%). Immunopheresis-related G3-4 AEs were CVC complications (29%), hypophosphatemia (14%) and hypercalcemia (14%). Conclusions: The combination of LW-02-column immunopheresis and weekly chemotherapy procedure was shown to be generally safe and provided early, promising signs of antitumor activity in heavily pretreated mTNBC patients with short life expectancy. Further clinical evaluation of the antitumor activity of LW02-based immunopheresis combined chemotherapy is ongoing; however, due to myelotoxicity, the chemotherapy regimen will be adapted accordingly. Clinical trial information: NCT04004910.