Efficacy and safety of PD-1 blockade with JS001 in patients with advanced neuroendocrine neoplasms: a non-randomized, open-label, phase 1b trial

Date 22 October 2018
Event ESMO 2018 Congress
Session Proffered paper session - NETs and endocrine tumours
Topics Neuroendocrine Tumours
Clinical Research
Immunotherapy
Presenter Panpan Zhang
Citation Annals of Oncology (2018) 29 (suppl_8): viii467-viii478. 10.1093/annonc/mdy293
Authors P. Zhang1, M. Lu1, J. Li1, L. Shen2
  • 1Gi Department, Beijing Cancer Hospital, 100142 - Beijing/CN
  • 2., Beijing Cancer Hospital, Beijing/CN

Abstract

Background

We aimed to assess the safety and antitumor activity of JS001 in patients with recurrent or metastatic NENs.

Methods

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.

Results

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.

Conclusions

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.

Funding

Shanghai Junshi Bioscience Co.,Ltd.

Editorial Acknowledgement

The study was supported by Shanghai Junshi Bioscience Co.,Ltd.

Disclosure

All authors have declared no conflicts of interest.