Abstract CT542: Preliminary safety and efficacy results of KN046 in combination with KN026 in patients with locally advanced unresectable or metastatic HER2-positive solid cancer

Abstract Except breast cancer and gastric cancer, HER2 gene amplification or overexpression is also expressed in other solid tumors, including but not limited to colorectal cancer (CRC), non-small cell lung cancer (NSCLC), gallbladder cancer, renal pelvis cancer and pancreatic cancer. The reports of immunotherapy combined with HER2-targeted therapy are limited. KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1 and CTLA4 interaction with CD80/CD86. KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. Here the preliminary safety and efficacy results of KN046 in combination KN026 were reported in patients with locally advanced unresectable or metastatic other solid tumors who received ≥ 1 line prior systemic therapy. Methods: HER2-positive locally advanced unresectable or metastatic other solid tumors with progression after ≥ 1 line of prior systemic therapy were recruited, including 14 CRC patients, 4 NSCLC patients, 4 gallbladder cancer patients, 1 renal pelvis cancer patient and 1 pancreatic cancer patient. These patients were by KN046 (iv. 5 mg/kg Q3W) plus KN026 (iv. 30 mg/kg Q3W, loading on C1D1, D8) until progression, unacceptable toxicity, or patient withdrawal. Efficacy was assessed according to RECIST 1.1 Q6W. The primary endpoint was objective response rate (ORR). Results: As of the August 10th, 2021, 24 non-breast or non-gastric cancer patients with the median age of 56 years (range: 37-66) were enrolled. 20 and 24 patients were evaluable for overall response and safety, respectively. The ORR was 55.0% (11 of 20, 95% CI: 31.5-76.9). And the disease control rate (DCR) was 85.0% (17 of 20, 95% CI 62.1-96.8). The 6-month progression-free survival (PFS) rate was 84.1%. 11 CRC patients were evaluable for overall response. The ORR and DCR in CRC was 45.5% (5 of 11, 95% CI: 16.7-76.6) and 90.9% (10 of 11, 95% CI 58.7-99.8), respectively. Twenty of total 24(87.9%) patients suffered from treatment-related adverse events (TRAEs) of any grade. Total 4 of 24 (16.7%) patients had experienced ≥grade 3 TRAEs, including 4 cases related to KN046 and 3 cases related to KN026. The most common (≥10%) TRAEs were infusion related reaction (29.2%), diarrhea (19.4%), alanine aminotransferase increased (16.7%), aspartate aminotransferase increased (16.7%), vomiting(12.5%) and decreased appetite (12.5%). No treatment-related deaths were observed. Conclusion: This chemotherapy-free regimen of KN046 in combination with KN026 has shown promising clinical efficacy and manageable toxicity in HER2-positive non-breast and non-gastric solid tumors with ≥ 1 line prior systemic therapy. The trial is currently ongoing. ClinicalTrials.gov Number, NCT04521179 Citation Format: Jifang Gong, Lei Chen, Meili Sun, Yanming Zhang, Jieer Ying, Xiangcai Wang, Mingli Ni, Zhixiang Zhuang, Baohong Guo, Long Xiao, Summer Xia, Lin Shen. Preliminary safety and efficacy results of KN046 in combination with KN026 in patients with locally advanced unresectable or metastatic HER2-positive solid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT542.