Reference Detail

Ref Type

Journal Article

PMID

(36469563)

Authors

Zhou Y, Yang Q, Dong Y, Ji T, Zhang B, Yang C, Zheng S, Tang L, Zhou C, Qian G, Huang Y, Yu W, Li H, Wang Y, He A, Shen Z, Bao Q, Hua Y, Bai H, Zhao J, Li X, Dai X, Zhang J, Hu H, Yao Y

Title

First-in-Maintenance Therapy for Localized High-Grade Osteosarcoma: An Open-Label Phase I/II Trial of the Anti-PD-L1 Antibody ZKAB001.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	29	4	2023 Feb 16	764-774	Clin Cancer Res

URL

Abstract Text

We investigated the safety and preliminary efficacy of anti-PD-L1 antibody (ZKAB001) as maintenance therapy for localized patients with high-grade osteosarcoma to reduce the risk of recurrence and metastasis.This open-label Phase I/II study was divided into dose-escalation Phase I and expansion Phase II. Phase I used a 3+3 design with ZKAB001 at three escalating doses ranging: 5, 10, 15 mg/kg every 2 weeks in 9 patients with localized high-grade osteosarcoma and Phase II tested 10 mg/kg in 12 patients for up to 24 cycles. Primary endpoints were safety and tolerability assessed using CTCAE4.0.3.Between October 2018 and 2019, 21 eligible patients were enrolled and accepted ZKAB001 treatment: 9 in the dose-escalation phase, and 12 in expansion phase. Six patients with disease progression withdrew from this study and follow-up is ongoing. The MTD was not defined in Phase I. All doses had a manageable safety profile. The recommended dose in Phase II was set at 10 mg/kg. Most frequent immune-related adverse events were thyroiditis (76.2%) and dermatitis (42.9%). Only 1 (4.8%) of 21 patients had a Grade 3 skin rash. The median 3-year event-free survival (EFS) and overall survival (OS) were not established; however, 24-month EFS was 71.4% (95% confidence interval, 47.2-86.0) and 2-year OS was 100%. Preliminary efficacy data showed EFS benefits in patients with PD-L1 positive or an MSI-H sub-population.Switching to maintenance using ZKAB001 showed an acceptable safety profile and provided preliminary evidence of clinical activity in localized patients with osteosarcoma.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
ZKAB001	ZKAB001	1	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
ZKAB001		ZKAB 001\|ZKAB-001\|Socazolimab\|STIA1014\|STI-A1014\|STI A1014	PD-L1/PD-1 antibody 122	ZKAB001 is a monoclonal antibody targeting CD274 (PD-L1), which potentially induces antibody-dependent cell-mediated cytotoxicity (ADCC) and inhibition of tumor growth (PMID: 36469563).

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	osteosarcoma	predicted - sensitive	ZKAB001	Case Reports/Case Series	Actionable	In a Phase I/II trial, ZKAB001 treatment resulted in improved 6, 12, and 24-month event-free survival (100%) in osteosarcoma patients with CD274 (PD-L1) expression (TPS >/= 1%) compared to a 6-month EFS of 84.5% and 12 and 24-month EFS of 64.7% in patients without CD274 (PD-L1) expression (PMID: 36469563).	36469563