ESMO Breast Cancer 2023
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 roll in patients with BRCA1 mutations and other tumor profiles.