Serplulimab, a novel anti-PD-1 antibody, in patients with microsatellite instability-high solid tumours: an open-label, single-arm, multicentre, phase II trial

Shukui Qin, Jin Li, Haijun Zhong, Chuan Jin, Lili Chen, Xianglin Yuan, Qingxia Fan, Kehe Chen, Peiguo Cao, Jianjun Xiao, Da Jiang, Tao Zhang, Hongyu Zhang, Xicheng Wang, Wei Wang, Lin Han, Qingyu Wang, Jun Zhu, Serplulimab-MSI-H Investigators, Shukui Qin, Jin Li, Haijun Zhong, Chuan Jin, Lili Chen, Xianglin Yuan, Qingxia Fan, Kehe Chen, Peiguo Cao, Jianjun Xiao, Da Jiang, Tao Zhang, Hongyu Zhang, Xicheng Wang, Wei Wang, Lin Han, Qingyu Wang, Jun Zhu, Serplulimab-MSI-H Investigators

Abstract

Background: Microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumours have a high response rate to immunotherapy. Antitumour activity and safety of serplulimab, a novel humanised anti-PD-1 monoclonal antibody, were evaluated in this phase II study.

Methods: In this ongoing, single-arm, open-label, phase II trial, patients with previously treated unresectable or metastatic MSI-H/dMMR solid tumours received intravenous serplulimab 3 mg/kg every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate (ORR) assessed by an independent radiological review committee per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included additional efficacy measures, safety, and tolerability.

Results: As of 9 January 2021, 108 patients were enrolled, and 68 patients with confirmed MSI-H solid tumours were included in the main efficacy analysis population (MEAP). The median follow-up duration in the MEAP was 7.7 months, with an ORR of 38.2% (95% confidence interval, 26.7-50.8). Of the 108 patients, grade ≥3 treatment-emergent adverse events were reported in 53 (49.1%) patients; immune-related adverse events occurred in 52 (48.1%) patients.

Conclusions: Serplulimab demonstrates a durable antitumour effect and a manageable safety profile in previously treated patients with MSI-H solid tumours. Serplulimab is a promising tissue-agnostic treatment for previously treated MSI-H solid tumours.

Trial registration: NCT03941574.

Conflict of interest statement

LH, QW, and JZ are employees of Shanghai Henlius Biotech, Inc. All other authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1. Participant flow diagram.
Fig. 1. Participant flow diagram.
MEAP main efficacy analysis population, MSI-H microsatellite instability-high, SAP sensitivity analysis population, SIEAP special-interest efficacy analysis population, SS safety set.
Fig. 2. Best percentage change from baseline…
Fig. 2. Best percentage change from baseline in target lesion size assessed by IRRC per RECIST v1.1.
Analysis was based on the main efficacy analysis population. Three patients did not have tumour assessments and were therefore excluded. IRRC independent radiological review committee, RECIST Response Evaluation Criteria in Solid Tumors.
Fig. 3. Survival in the MEAP and…
Fig. 3. Survival in the MEAP and SIEAP.
Kaplan–Meier curves of progression-free survival (a) and overall survival (b). Tumour response was assessed by IRRC per RECIST v1.1. CI confidence interval, IRRC independent radiological review committee, MEAP main efficacy analysis population, mo month, NR not reached, OS overall survival, PFS progression-free survival, RECIST Response Evaluation Criteria in Solid Tumors, SIEAP special-interest efficacy analysis population.

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