Abstract PD11-10: PD11-10 Efficacy, Safety, and Tolerability of KN046 (an anti-PD-L1/CTLA-4 Bispecific Antibody) in combination with Nab-paclitaxel in Metastatic Triple-negative Breast Cancer (mTNBC):Final results of the Phase II trial
Authors: Li Qiao , Zhang Qingyuan , Zhang Yue , Ouyang Quchang , Liu Qiang , Sun Tao , Ye Feng , Zhang Baochun , Xu Ting , Xia Summer , Zhang Karl , Zhang Bangyong , Xu Binghe 
Published: March 2023

Abstract
Background: Despite recent FDA approval of immune checkpoint inhibitor pembrolizumab and drug-antibody conjugate in the treatment of mTNBC, the overall survival benefit of these patients remains modest. We conducted a phase 2 study to assess the efficacy and safety of anti-PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel in mTNBC patients (pts) regardless of PD-L1 status. Preliminary results have been delivered in 2021 AACR[1], here we reported the final results of the progression-free survival (PFS) and overall survival (OS) analysis. 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. The primary endpoint included objective response (ORR) and duration of response (DoR), secondary included disease control rate (DCR), clinical benefit rate (CBR), PFS, 1-year/2-year OS rate and safety/tolerability. Results: As of May 9, 2022 (cut-off date), 27 pts were enrolled into DL1 (n=16) and DL2 (n=11). Median patient age in the study was 50 years (range, 33-70 years). At baseline, 52% and 48% of patients had ECOG PS of 0 and 1, respectively. By the cut-off date, there are 1 pts under treatment and 16pts alive. The median study follow-up time was 26.3 months (95% CI, 20.7 - 29.8). Based on the intent-to-treatment (ITT) population, the confirmed ORR was 33.3% (95% CI, 16.5% - 54.0%), DCR was 88.9% (95% CI, 70.8% - 97.7%), and CBR was 48.1% (95% CI, 28.7% - 68.1%), which remained stable compared with last reported in 2021 [1]. The DoR was 11.9 (95% CI, 5.6 - NR) months. The median PFS was 7.3 (95% CI, 3.7 - 13.7) months. The median OS is immature, the preliminary result is 27.7 (95% CI, 14.8 - NR) months, and the 2-year OS rate was 60.1% (95%CI, 37.2% - 76.9%). Among the 11 pts with PD-L1 positive (≥1% IC), confirmed ORR was 45.5% (95%CI, 16.7% - 76.6%) and mPFS was 8.61 (95%CI, 1.6 - 13.8) months. Both PD-L1 positive and negative pts derived OS benefit from the combination treatment, with the 2-year OS rate of 57.14% (95%CI, 25.4% - 79.6%) and 62.5% (95%CI, 22.9% - 86.1%) respectively. Patients tolerated well to combination therapy in this trial. The most common reported treatment related adverse event (TRAEs) were ALT elevation (13 pts, 48%), AST elevation (12 pts, 44%), pyrexia (9 pts, 33%), neutropenia (8 pts, 30%), and anemia (7 pts, 26%). Grade ≥3 TRAEs (≥10%) were neutropenia (7 pts, 26%), leukopenia (6 pts, 22%) and AST elevation (5 pts, 15%). 13 pts (48%) experienced immune related adverse events (irAEs), and only 3 irAEs (11%) were grade 3. The incidence of SAE was 33%, with no TRAE leading to death. Conclusions: The combination therapy of KN046 plus nab-paclitaxel has shown favorable clinical efficacy in mTNBC, especially in PD-L1 positive patients. By the cut-off date, the mOS is not mature and there is still more than half of pts alive, which demonstrated an encouraging 2-year OS rate. Pts in this trial tolerated well to the combination therapy and safety profile was manageable. Clinical trial information: NCT03872791 Reference 1. Cancer Res (2021) 81 (13_Supplement): 1660.
Citation Format: Qiao Li, Qingyuan Zhang, Yue Zhang, Quchang Ouyang, Qiang Liu, Tao Sun, Feng Ye, Baochun Zhang, Ting Xu, Summer Xia, Karl Zhang, Bangyong Zhang, Binghe Xu. PD11-10 Efficacy, Safety, and Tolerability of KN046 (an anti-PD-L1/CTLA-4 Bispecific Antibody) in combination with Nab-paclitaxel in Metastatic Triple-negative Breast Cancer (mTNBC):Final results of the Phase II trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-10.