SUZHOU, China, Feb. 6, 2024 /PRNewswire/ -- Alphamab Oncology (stock code: 9966.HK) announced that the phase Ⅱclinical research results of anti- PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel as first-line treatment in advanced triple-negative breast cancer (TNBC) were published online in the renowned journal Nature Communications (IF: 16.6, JCR Q1). Professor Binghe Xu from Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College is the corresponding author of this paper.

Corresponding Author: Binghe Xu,
First author: Qiao Li

KN046-203 is a phase II, open label, multi-center, multi-cohorts clinical study, evaluating the efficacy, safety, and tolerability of KN046 in combination with nab-paclitaxel in patients with TNBC as first-line treatment. A total of 27 female patients who were systemic treatment na?ve for locally advanced inoperable or metastatic TNBC were enrolled.

As of August 21, 2022, based on the Independent Review Committee (IRC) evaluation, the objective response rate (ORR) from 25 efficacy evaluable TNBC patients was 44.0% (95% CI: 24.4~65.1%), the disease control rate (DCR) was 96.0% (95% CI: 79.7~99.9%), the clinical benefit rate (CBR) was 52.0% (95% CI: 31.1~72.2%) and the median DOR was not mature. The progression-free survival (PFS) and overall survival (OS) was analyzed on intention-to treat (ITT) population. The median PFS was 7.33 months (95%CI: 3.68~11.07 months). Among the patients with PD-L1 expression ≥1%, the median PFS was 8.61 months (95%CI, 1.61 - NE months). The median OS result was 30.92 months (95% CI, 14.75 - NE months), and the 2-year OS rate was 60.1% (95%CI, 37.2~76.9%). Both PD-L1 negative and positive patients could derive OS benefit from the therapy.

Among the 27 evaluable patients, Grade 3-4 treatment-related adverse events (TRAEs) occurred in 18 patients (66.7%). Treatment-related serious adverse events (TRSAEs) occurred in 6 patients (22.2%). Immune-related adverse events (irAEs) occurred in 13 patients (48.1%). Most irAEs were Grade 1 or 2. Grade ≥3 irAEs were reported in 3 patients, 2 patients with Grade 3 immune-mediated liver disease, and 1 patient with Grade 3 rash.

Conclusion: KN046 combined with nab-paclitaxel in the first-line treatment of TNBC showed encouraging PFS and OS. Patients received combination therapy were well tolerated and the safety profile was manageable.

About KN046

KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Alphamab. Its innovative designs include: a novel mechanism - CTLA-4 fused with PD-L1 single domain antibody; engineered to target the tumor microenvironment with high PD-L1 expression, and Treg (suppress tumor immunity) clearing function.