First-in-maintenance therapy for localized high-grade osteosarcoma: an open-label phase I/II trial of the anti-PD-L1 antibody ZKAB001.

PURPOSE
We investigated the safety and preliminary efficacy of anti-PD-L1 antibody (ZKAB001) as maintenance therapy for localized high-grade osteosarcoma patients to reduce the risk of recurrence and metastasis.


PATIENTS AND METHODS
This open-label phase I/II study was divided into dose-escalation phase I and expansion phase II. Phase I utilized 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.


RESULTS
Between October 2018 and October 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 maximum tolerated dose (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 one (4.8%) of 21 patients had a Grade 3 skin rash. The median 3-year EFS and OS were not established, however, 24-month EFS was 71.4% (95% CI: 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.


CONCLUSIONS
Switching to maintenance using ZKAB001 showed an acceptable safety profile and provided preliminary evidence of clinical activity in localized osteosarcoma patients.