ASCO

A proof-of-concept study of LXP5268 as an add-on neoadjuvant chemotherapy in
patients with early-stage triple-negative breast cancer.

Liang Chih Liu Sr., Tzong-Der Way, Chin-Hua Lin, Ya-Hui Chen, Pin-Hung Kuo, Chung-Hsin Tseng, Chiu-Heng Chen; China Medical University Hospital, Taichung City, Taiwan;
China Medical University, Taichung City, Taiwan; LAUNXP Biomedical Co., Ltd, Taichung City, NA, Taiwan; LAUNXP Biomedical Co., Ltd, Taichung City, Taiwan

Background: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive subtype
characterized by a high risk of mortality and a poor prognosis. The 2019 ASCO and St. Gallen
International Consensus Guidelines strongly recommend neoadjuvant chemotherapy (NACT)
for early-stage TNBC. Previous studies indicated that NACT improved overall and disease-free
survival in early-stage TNBC. LXP5268, a drug in the 505(b)(2) category, has demonstrated
efficacy in reducing tumor size in animal models. Our study aims to assess whether combining
LXP5268 with NACT enhances anti-tumor efficacy and tumor shrinkage rates in early-stage
TNBC patients. Methods: Enrolled patients had untreated stage II-III TNBC. NACT consisted of
docetaxel every 3 weeks for four cycles, followed by epirubicin plus cyclophosphamide every
3 weeks for an additional four cycles (24 weeks total). In the LXP5268 add-on NACT
(LXP5268+NACT) group, patients took LXP5268 orally once daily with NACT. After treatment,
we analyzed tumor objective response rate (ORR), shrinkage rate by CT images, and adverse
events (AEs) diagnosed by the principal investigator. Whole-exome sequencing (WES) was
performed on 6 subjects in the LXP5268+NACT group, identifying potential germline variants
and biomarkers, clinically interpreted following ACMG/AMP 2015 guidelines. Results: Both
groups had similar baseline characteristics. LXP5268+NACT subjects (54.8 6 7.2 years) and
NACT subjects (59.3 6 9.8 years) showed significant age differences (p,0.001). The ORR was

100% in both the LXP5268+NACT group (3 pathological complete response, pCR and 4 path-
ological partial response, pPR) and NACT group (6 pPR). The tumor shrinkage rate was sig-
nificantly higher in the LXP5268+NACT group at 77.3% 6 21.8 compared to 43.4% 6 12.8 in the

NACT group (p, 0.001). Moreover, subjects in the LXP5268+NACT group with a tumor reduc-
tion exceeding 50% surpassed those in the NACT group. AEs included neutropenia (85.7%),

constipation (66.7%), and insomnia (66.7%), all grade 1. Interestingly, mutation in XIRP2
correlated with higher tumor shrinkage rate. Conclusions: LXP5268 combined with NACT was
more effective than NACT alone for early-stage TNBC, without increasing AEs. These results
highlight LXP5268’s potential in TNBC therapy. Previous studies indicated XIRP2 mutations in
metastatic breast cancer. LXP5268+NACT achieved pCR in XIRP2-mutated patients. Future
clinical trials will expand to enhance result verification accuracy. Clinical trial information:
CMUH106-REC3-145. Research Sponsor: LAUNXP Biomedical Co., Ltd.

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