Reference Detail

Ref Type

Journal Article

PMID

(37263673)

Authors

Ma Y, Xue J, Zhao Y, Zhang Y, Huang Y, Yang Y, Fang W, Guo Y, Li Q, Ge X, Sun J, Zhang B, Zhang Y, Xiao J, Zhang L, Zhao H

Title

Phase I trial of KN046, a novel bispecific antibody targeting PD-L1 and CTLA-4 in patients with advanced solid tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal for immunotherapy of cancer	11	6	2023 Jun		J Immunother Cancer

URL

Abstract Text

KN046 is a novel bispecific antibody targeting programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). This multicenter phase I trial investigated the safety, tolerability, pharmacokinetics (PK), and efficacy of KN046 in patients with advanced solid tumors.Patients who failed standard treatment were included. KN046 was administered at doses of 1, 3, and 5 mg/kg every 2 weeks (Q2W), 5 mg/kg every 3 weeks (Q3W), and 300 mg Q3W based on the modified toxicity probability interval method in the dose-escalation phase; the recommended dose was used in the expansion phase. Primary objectives were maximum tolerated dose (MTD) and recommended phase II dose (RP2D) in escalation and preliminary efficacy in expansion. Secondary objectives included PK, pharmacodynamics, safety, and tolerability of KN046. We also explored biomarkers based on PD-L1 expression, multiplex immunofluorescence (mIF) staining, and RNAseq-derived nCounter platform.Totally, 100 eligible patients were enrolled, including 59 with nasopharyngeal carcinoma (NPC), 36 with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), and those with other advanced solid tumors. The most common treatment-related adverse events (TRAEs) were rash (33.0%), pruritus (31.0%), and fatigue (20.0%). Grade ≥3 TRAEs were observed in 14.0% of participants. No dose-limiting toxicity occurred in the dose-escalation phase, and the MTD was not reached. The RP2D was determined as 5 mg/kg Q2W according to the pharmacokinetic-pharmacodynamic model, the preliminary exposure-response analysis, and the overall safety profile. Among 88 efficacy-evaluable participants, the objective response rate (ORR) was 12.5%, and the median duration of response was 16.6 months. In the NPC subgroup, the ORR was 15.4%, and the median overall survival (OS) was 24.7 (95% CI 16.3 to not estimable) months. In the EGFR-mutant NSCLC subgroup, the ORR was 6.3%. mIF analysis results showed patients with high CD8 expression showed longer median OS (27.1 vs 9.2 months, p=0.02); better prognosis was observed in patients with high CD8 and PD-L1 expression.KN046 was well tolerated and showed promising antitumor efficacy in advanced solid tumors, especially in patients with NPC. The combination of both CD8 and PD-L1 expression improved the prediction of KN046 response.NCT03733951 .

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
KN046	KN046	1	1

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
KN046		KN 046\|KN-046\|Erfonrilimab	CTLA4 Antibody 32 Immune Checkpoint Inhibitor 149 PD-L1/PD-1 antibody 122	KN046 is a bispecific monoclonal antibody that targets PD-L1 (CD274) expressed on tumor cells and CTLA-4 on T lymphocytes, potentially leading to enhanced antitumor immune response (PMID: 37263673).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 positive	Advanced Solid Tumor	predicted - sensitive	KN046	Phase I	Actionable	In a Phase I trial, KN046 treatment was well tolerated and resulted in an objective response rate of 12.5% (11/88; all partial responses) and median duration of response of 16.6 months in patients with advanced solid tumors, patients with CD274 (PD-L1)-positive tumors experienced longer median progression-free survival (2.5 vs 1.3 months, p=0.0098) and overall survival (19.9 vs 5.4 months, p=0.014) than those with CD274 (PD-L1)-negative tumors ( (PMID: 37263673; NCT03733951).	37263673