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, Junning Cao, Qingyuan Zhang, Nong Xu, Yanqiu Zhao, Baocai Xing, Zhanhui Miao, Yilong Wu, Hongming Pan, Quanli Gao, Xingya Li, Baorui Liu, Wei Li, Zhidong Pei, Hongqiang Xia, Qinzhou Qi, Hangjun Dai, Qingmei Shi, Jianxin Yang, Jin Li, Lin Shen, Jifang Gong, Junning Cao, Qingyuan Zhang, Nong Xu, Yanqiu Zhao, Baocai Xing, Zhanhui Miao, Yilong Wu, Hongming Pan, Quanli Gao, Xingya Li, Baorui Liu, Wei Li, Zhidong Pei, Hongqiang Xia, Qinzhou Qi, Hangjun Dai, Qingmei Shi, Jianxin Yang, Jin Li, Lin Shen

Abstract

Background: 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.

Methods: Eligible 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).

Results: As 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.

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.

Keywords: Immunotherapy; PD-L1; Solid tumor; Sugemalimab.

Conflict of interest statement

Dr. Y. Wu reported receiving honoraria from AstraZeneca, Eli Lilly and Company, Pfizer, Roche, and Sanofi. H. Xia, Q. Qi, H. Dai, Q. Shi, and J. Yang are paid employees of CStone Pharmaceuticals. Other authors declared no conflict of interest.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Study profile. PK, pharmacokinetics
Fig. 2
Fig. 2
Tumor response in each disease cohort in phase 1b. Each bar represents one patient. ≥ 2L, second-line or after; 1L, first-line; CC/GBC, cholangiocarcinoma or gallbladder carcinoma; HCC, hepatocellular carcinoma; MSI-H/dMMR, solid tumors with MSI-H/dMMR phenotype; GAC/GEJAC, gastric adenocarcinoma or gastroesophageal junction adenocarcinoma; ESCC, esophageal squamous cell carcinoma; NSCLC, non-small cell lung cancer. PR, partial response; SD, stable disease; PD, progressive disease

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Source: PubMed

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