Abstract 1456
Background
KN035 is a novel fusion protein of anti-PD-L1 single domain antibody and Fc, formulated for subcutaneous (SC) injection. A phase 1 dose escalation study was performed in the USA to evaluate and characterize the safety and tolerability, MTD, PK, PD and preliminary antitumor activity of single agent KN035 in patients (pts) with locally advanced or metastatic solid tumors.
Methods
A modified 3 + 3 dose-escalation design was adopted with the DLT evaluation period of 28 days after the first dose of KN035, with 8 dose levels planned at 0.01, 0.03, 0.1, 0.3, 1.0, 2.5, 5 and 10 mg/kg SC weekly. Single patient cohorts were planned at the dose levels of 0.01, 0.03 and 0.1 mg/kg/dose; unless a ≥ G2 drug-related AE occurred in the first 28-day cycle, then 2 additional pts would be enrolled. Response was evaluated by RECIST 1.1 every 12 weeks.
Results
As of May 4, 2018, a total of 18 pts have been enrolled (including prostate cancer [n = 5], non-small cell lung cancer (NSCLC) [n = 2], breast cancer [n = 2], gastrointestinal cancers [n = 5], melanoma, cervical, head and neck and bladder cancer). Planned maximum dose of 10 mg/kg has been administered (n = 3) without DLT. Most common treatment-related AEs were G1/2 (61.1%). Adverse Events experienced by more than 1 patient were fatigue (n = 4, 22%), aspartate aminotransferase increased, alanine aminotransferase increased and nausea (each n = 2, 11%). The only treatment–related G3 AE was lymphopenia (n = 1), which occurred at 0.1 mg/kg and resolved one week later despite continued dosing. Overall, the emergence of AEs was not dose-related. The exposure to KN035 was dose-dependent and increased proportionally. Average half-life (t1/2) of KN035 was approximately 200 hours. Among 13 evaluable pts, 2 pts had confirmed PR, including 1 NSCLC pt at 0.3mg/kg (response duration 9 months) and 1 MSI-H prostate cancer pt at 2.5mg/kg (ongoing response 5 months), and 5 pts achieved SD.
Conclusions
KN035 exhibits a favorable safety profile in patients with advanced malignancies and preliminary results demonstrate encouraging anti-tumor activity.
Clinical trial identification
Protocol Number: KN035-US-001, NCT02827968.
Legal entity responsible for the study
3D Medicines (Sichuan) Co., Ltd.
Funding
3D Medicines (Sichuan) Co., Ltd.
Editorial Acknowledgement
Disclosure
W. Harb: Consulting for advisory role (Institution/Self): Boston Biomedical, Pfizer, Vigeo. R. Dong: CMO: 3D Medicines (Sichuan) Co., Ltd; Advisor: Newbay Biopharma; CEO: Haihe Biopharma. J. Gong: Independent board of directors: Staidson (Beijing) Biopharmaceuticals Co., Ltd, Shandong Jincheng Pharmaceutical Group Co., Ltd. And Accendatech Co, Ltd. All other authors have declared no conflicts of interest.