Safety, antitumor activity and biomarkers of sugemalimab in Chinese patients with advanced solid tumors or lymphomas: results from the first-in-human phase 1 trial

Jifang Gong,Hangjun Dai,Baocai Xing,Zhanhui Miao,Jin Li,Hong-Qiang Xia ,Wei Li,Zhijun Pei ,Qingmei Shi,Baorui Liu,Junning Cao,Quanli Gao,Yi‐Long Wu ,Hongming Pan,Qingyuan Zhang,Xingya Li,Yanqiu Zhao,Jianxin Yang,Nong Xu,Qinzhou Qi,Lin Shen

doi:10.1007/s00262-021-03102-3

Abstract

BackgroundThis first-in-human phase 1 trial is to evaluate the safety, pharmacokinetics, preliminary efficacy, and biomarkers of sugemalimab, a full-length, fully human anti-PD-L1 monoclonal antibody, in Chinese patients with advanced malignancies.MethodsEligible patients with unresectable advanced or metastatic solid tumors or lymphomas were enrolled in phase 1a to receive sugemalimab following a modified 3 + 3 design. The primary endpoints included safety, tolerability, and the recommended Phase 2 dose (RP2D). In phase 1b, patients with 7 selected types of tumor received sugemalimab at the RP2D alone (monotherapy cohorts) or in combination with standard-of-care (SOC) chemotherapy (combination cohorts). The primary endpoint of phase 1b was investigator-assessed objective response rate (ORR).ResultsAs of 19 February 2020, 29 and 178 patients were treated in phase 1a and 1b, respectively. No dose-limiting toxicities were observed in phase 1a, and the RP2D of sugemalimab was determined as 1200 mg fixed dose once every 3 weeks. Sugemalimab-related adverse events (AEs) were mostly (75.9%) grade 1–2 in phase 1a. Antitumor activity was observed across dose levels with an ORR of 24.1%. In phase 1b, 15.9% and 40.4% of patients in the monotherapy and combination cohorts, respectively, reported grade 3–5 sugemalimab-related AEs. Promising efficacy was observed in all combination cohorts, with ORRs ranging from 47.6 to 75.0%. Exploratory biomarker analysis did not indicate significant differences in responses at different PD-L1 expression/tumor mutation burden levels.ConclusionsSugemalimab was well-tolerated and showed promising antitumor activity as monotherapy or in combination with SOC chemotherapy in advanced malignancies.This trial was registered with ClinicalTrials.gov on Oct 18, 2017, number NCT03312842.

Highlights

Cancer has become the leading cause of death and a major barrier to extending life expectancy worldwide in the past decade [1]
As for the squamous and non-squamous non-small cell lung cancer (NSCLC) cohorts combined, 17 patients were evaluable for PD-L1 expression, and the objective response rate (ORR) was 50.0% in patients with PD-L1 tumor cells (TC) ≥ 1% and 71.4% in patients with PD-L1 TC < 1%. In this first-in-human trial, we demonstrated that sugemalimab was well tolerated, without any unexpected safety issues observed, and had promising antitumor activity in Chinese patients with advanced solid tumors and lymphomas
During phase 1a dose-escalation, we demonstrated that sugemalimab can be safely administrated at doses from 3 mg/kg Q3W to 40 mg/kg Q3W

Summary

Introduction

Cancer has become the leading cause of death and a major barrier to extending life expectancy worldwide in the past decade [1]. This first-in-human phase 1 trial is to evaluate the safety, pharmacokinetics, preliminary efficacy, and biomarkers of sugemalimab, a full-length, fully human anti-PD-L1 monoclonal antibody, in Chinese patients with advanced malignancies. In phase 1b, 15.9% and 40.4% of patients in the monotherapy and combination cohorts, respectively, reported grade 3–5 sugemalimab-related AEs. Promising efficacy was observed in all combination cohorts, with ORRs ranging from 47.6 to 75.0%. Conclusions Sugemalimab was well-tolerated and showed promising antitumor activity as monotherapy or in combination with SOC chemotherapy in advanced malignancies. This trial was registered with ClinicalTrials.gov on Oct 18, 2017, number NCT03312842

Methods

Results

Conclusion