We aimed to assess the safety and antitumor activity of JS001 in patients with recurrent or metastatic NENs.
In this an open-label, non-randomized, phase 1b trial(NCT03167853), we enrolled patients with measurable advanced nonfunctional NENs (Ki67≥10%) that had failed standard therapy. The benchmark of PDL1-positivity was set at ≥ 5% tumor cell expression or > 1% immune cells(membrane and cytoplasm) on an autostainer (BOND-MAX, LEICA). JS001 was administered at a dose of 3 mg/kg every 2 weeks for up to 2 years or until confirmed progression, intolerable toxicity, or withdrawal of consent. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary endpoint was objective response rate (ORR) per RECIST v1.1 and irRECIST.
23 patients with advanced NEN were enrolled from April 2017 to March 2018; of these 2 patients were NET, 3 NET G3, 15 NEC and 3 MANEC. The primary site was pancreas in 7 patients, gastrointestinal tract in 11 patients, and other sites in 5 patients. The median age was 59 years(range, 38-77) and 14(60.9%) patients were male. 5(21.7%) patients received ≥ 3 prior lines of therapy. PD-L1 positive rate was 28.6%(6/21). 21 patients were evaluated as of the data cutoff. The ORR was 28.6%(6/21) in all, 40%(2/5) in NET and 25%(4/16) in NEC, and the DCR was 47.6% (10/21) for irRECIST; 4 patients (2NET; 2NEC) achieved PR for an ORR of 19.0%, and the DCR was 38.1%(8/21) for RECIST. Of 6 PD-L1-positive patients (2NET; 4NEC), the ORR was 83.3%(5/6) for irRECIST and 66.7% (4/6) for RECIST. A reduction in tumor size (sum of the longest tumor diameters) was documented for 42.8%(9/21). Median progression-free survival was 2.8 months(95%CI 1.6-4.0months). The duration of response of the 4 patients were for 2.3+, 3.3, 2.8+ and 2.3+ months, and the inconsistent 2 patients were 2.3+ and 2.8 months for RECIST. The most frequent treatment-related adverse events(TRAEs) was grade 1 fatigue(n = 8), increased ALT or AST(n = 6), and hypothyroidism(n = 4). Grade 3 TRAEs occurred in 2(9%) patients with peritonitis. No patients had grade ≥4 TRAEs.
JS001 demonstrated antitumor activity and manageable safety profiles in pretreated patients with advanced NENs.
Clinical trial identification
NCT03167853. Release date: April 6, 2017.
Legal entity responsible for the study
Beijing Cancer Hospital.
Shanghai Junshi Bioscience Co.,Ltd.
The study was supported by Shanghai Junshi Bioscience Co.,Ltd.
All authors have declared no conflicts of interest.