The preliminary efficacy and safety data of KN046 in patients failed on prior immune checkpoint inhibitors therapy.

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3020 Background: KN046 is a bispecific antibody that blocks PD-L1 and CTLA-4 by interaction with PD1 and CD80/CD86. KN046-CHN-001 (NCT03529526) is a, dose escalation and expansion phase Ia/Ib clinical trial in China. Here we reported safety, tolerability and preliminary efficacy in patients failed on prior immune checkpoint inhibiters (ICIs) treatment. Methods: Patients progressed on ICIs (including but not limited to antibodies targeting PD-1, PD-L1, OX40, et al) with pathologically confirmed solid tumor, ECOG 0-1, measurable lesion per RECIST v1.1, no immune-related adverse events (IRAEs) led to ICIs discontinuation, were enrolled and received intravenous KN046 treatment across four dose levels including 3.0 mg/kg (n = 3) and 5.0 mg/kg (n = 20) Q2W; and 5.0 mg/kg (n = 4), 300.0 mg flat dose (n = 2) Q3W. Safety and tolerability were assessed per NCI-CTCAE v5.0. Treatment-emergent AEs (TEAEs) and IRAEs were decided by investigators. Efficacy was evaluated by investigators per RECIST 1.1 every 6 weeks. Results: Twenty-nine who progressed on prior ICIs therapy were enrolled (25anti-PD-1 antibody; 3 anti-OX40 antibody; and 1 anti-CD137 antibody) and were included in the current analysis. Among 29 patients, 19 were nasopharyngeal cancer (NPC) and 9 were non-small cell lung cancer (NSCLC). The median duration of the exposure of KN046 was 12 weeks (range 2 to 40). Eleven patients remained on the treatment and 18 discontinued due to disease progression (n = 13), AE (n = 1), death (n = 1) and others (n = 3). Twenty-six (89.7%) patients experienced TRAEs of all grades and 2 (6.9%) experienced grade≥3 TRAEs (1 grade 3 anemia and 1 grade 3 infusion-related reaction). The most common (≥10%) TRAEs were pruritus (8, 27.6%), rash (8, 27.6%), asthenia (6, 20.7%), fatigue (6, 20.7%), pyrexia (5, 17.2%), infusion related reaction (4, 13.8%), alanine aminotransferase elevation (3, 10.3%) and white blood cell count elevation (3, 10.3%). Eleven (37.9%) patients experienced irAEs (with no grade≥3). Objective responses were occurred in 3 (12.0%, 25 evaluable) patients, disease control rate was 52.0% (10 stable disease). Median progression free survival was 2.69 (95%CI 1.31,5.52) months. Median overall survival was not reached. PFS rates for 3 and 6 Months were 41.0% (95%CI 18.5, 62.5) and 21.9% (95%CI 4.6, 47.3). OS rates for 6 and 9 months were88% (95%CI 57.2, 97.1) and 58.7% (95%CI 8.3, 89.2), respectively. Conclusions: Overall, KN046 showed a favorable safety profile and promising clinical benefit in advanced solid tumor patients who failed on prior ICIs therapy. Clinical trial information: NCT03529526 .