Background: Triple-negative breast cancer (TNBC) has the poorest outcome when compared to other subtypes of invasive breast cancer. IMpassion130 and Keynote-355 studies demonstrated improved clinical outcome when anti-PD-(L)-1 agents were combined with first line chemotherapies in PD-L1 positive TNBC. KN046 is a novel bispecific antibody that blocks PD-L1 and CTLA-4 pathways. Here we reported the interim results from an ongoing phase II study for KN046 in combination with nab-paclitaxel in pts with mTNBC.

Methods: This study enrolled pts with treatment-naïve locally advanced inoperable or metastatic TNBC. Eligible pts received nab-paclitaxel plus KN046 at two dose levels (DL1: KN046 3 mg/kg Q2W or DL2: KN046 5 mg/kg Q2W). Tumor response was evaluated Q8W per RECIST 1.1. PD-L1 expression was measured using SP142 assay.

Results: As of Oct. 29, 2020, 27 pts were enrolled into DL1 (n=16) and DL2 (n=11). 12 pts remained on the study and 15 pts discontinued treatment due to disease progression (n=8), death (n=1), adverse events (n=3) and other reasons (n=3). Patients tolerated well to KN046 plus nab-paclitaxel. No KN046 treatment related adverse event (TRAE) leading to death. TRAEs occurred in 27 (100%) pts, 13 (48.1%) were grade 3 or above. 11 (40.7%) pts experienced immune related adverse events (irAEs), including 2 patients experienced one grade 3 immune-mediated hepatic disorder and one grade 3 rash. The most common (≥ 20%) TRAE were AST increased (48%), ALT increased (48%), pyrexia (33%), neutrophil count decreased (30%), anaemia (26%), rash (26%) and white blood cell count decreased (26%). The most common (≥ 15%) grade 3 or above TRAEs were neutrophil count decreased (26%), white blood cell count decreased (22%) and AST increased (15%). Median PFS was 7.33 (4.04, NE) months and 12-month PFS rate was 38.3% (95% CI 19.7~74.6%). Median OS was not reached and 12-months OS rate was 80% (95% CI 61.4~100%). Among pts with PD-L1 positive (IC PD-L1≥1%) or PD-L1 status unknown tumors (exclude PD-L1 < 1%), Median PFS was 7.36 (95% CI 7.36, NE) months and 12-month PFS rate was 49.4% (95% CI 20.6~100%). 12-month OS rate was 90.9% (95% CI 75.1~100%).

Conclusions: KN046 combined with nab-paclitaxel is well tolerated and has shown favorable clinical efficacy in PD-L1 positive TNBC. Preliminary overall survival data is encouraging. Clinical trial information: NCT03872791

Citation Format: Binghe Xu, Qiao Li, Qingyuan Zhang, Yue Zhang, Quchang Ouyang, Yang Zhang, Qiang Liu, Tao Sun, June Xu, Jing Yang, Yue Yang, Xin Luo, Paul Kong, Ting Xu. Preliminary safety tolerability & efficacy results of KN046 (an anti-PD-L1/CTLA-4 bispecific antibody) in combination with Nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1660.