Endogenous tumor necrosis factor-α (TNF-α) has known anti-tumor effects; however, its activity is inhibited by soluble TNF receptors (sTNF-R1, -R2) produced by tumors. Systemic administration of recombinant TNF-α is limited due to unacceptable toxicity (except in isolated limb perfusion). Triple-negative breast cancers, including those with BRCA1/2 mutations, are candidates for novel immunotherapies. This study used extracorporeal apheresis (Immunopheresis) with the LW-02 Column to selectively remove sTNF-Rs from plasma to promote TNF-α’s anticancer action resulting in objective tumor responses.
This trial [NCT04004910] evaluated column performance (removal of sTNF-Rs), safety, and clinical efficacy (via RECIST 1.1) of LW-02 Column Immunopheresis in advanced breast cancer patients who failed 2 or more lines of systemic therapy. The trial enrolled 46 patients, 3 with germline BRCA1 mutations. Patients received LW-02 Column Immunopheresis 3x/week, as monotherapy or combined with chemotherapy for 16 weeks (or longer if patients were stable or improved clinically). Each treatment processed up to 2 plasma volumes.
Column performance data (from a prior data cutoff for 1700 procedures) found median reductions of sTNF-Rs from plasma after 30-minutes of Immunopheresis of 95.6% and 82.2% for sTNF-R1 and sTNF-R2, respectively. Safety and efficacy results are from data through 31 January 2023. About safety, of 665 AEs, 22 (3.3%) were deemed to have had a causal relationship to treatment with the LW-02 Column (including 2 SAEs). Median treatment durations were 9.7 and 14.5 wks for all patients and for patients treated ≥4 wks, respectively (and 55.9 wks for the subset of 3 patients with confirmed BRCA1 mutations, 2 are still being treated). Similarly, median OS was 17.9 and 27.6 and 55.9 wks for the same groups. CBR results for patients treated ≥4 wks was 39% and 67% for the 3 BRCA1 patients (the latter reflecting 1 CR and 1 PR).
LW-02 Column Immunopheresis is safe and effectively removes sTNF-Rs from advanced breast cancer patients and contributes to efficacy improvements. Additional trials will examine its role in patients with BRCA1 mutations and other tumor profiles.
NCT04004910.
Immunicom, Inc.
Immunicom, Inc.
P.J. Wysocki, P. Tomczak, T. Jankowski, T. Nowikiewicz: Financial Interests, Personal and Institutional, Principal Investigator: Immunicom, Inc. V. Manax, L. Florin, R. Segal, K.M. Djazouli, S. Bilgrami, A. Marleau, A. Ostrowski: Financial Interests, Personal, Full or part-time Employment: Immunicom, Inc.