Phase 1b Multicenter Study of SG001, a Humanized Anti-PD-1 Antibody, in Patients with Advanced Solid Tumors

Our plain-English summary of Phase 1b Multicenter Study of SG001, a Humanized Anti-PD-1 Antibody, in Patients with Advanced Solid Tumors, by J. Fang, O. Jiang, W. Li, et al (Drug Design, Development and Therapy, 2025).

The study

• Authors: J. Fang, O. Jiang, W. Li, J. Lin, M. Fang, Q. Li, W. Zhao, K. Wang, H. Shi, Z. Chen, J. Yu, X. Xing, M. Zhao, A. Liu, W. Wang, Z. Han, S. Xiang, X. Zhang, J. Li, C. Zhou
• Journal: Drug Design, Development and Therapy
• Published: 2025;19:10423-10435
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: SG001 is a humanized, IgG4 monoclonal antibody against human PD-1. This phase 1b study aimed to evaluate efficacy and safety of SG001 in advanced solid tumors.

Methods: Patients with previously treated solid tumors that are PD-L1-positive, and/or dMMR/MSI-H, and/or Epstein-Barr virus positive were enrolled in Cohort A, while patients with PD-L1-unselected malignant mesothelioma and PD-L1-unselected non-small cell lung cancer (NSCLC) were enrolled in Cohorts C and E, respectively. All patients in Cohorts A, C, and E received SG001 at a dose of 240mg every two weeks for 2 years or until disease progression, intolerable toxicities, or withdrawal of consent. The primary endpoint was the investigator-assessed overall response rate (ORR).

Results: A total of 87 patients were enrolled: 33 in Cohort A, 24 in Cohort C, and 30 in Cohort E. Investigator-assessed ORR was 39.4% in Cohort A, 12.5% in Cohort C, and 16.7% in Cohort E; corresponding median PFS values were 9.6, 4.1, and 4.0 months. The most common treatment-related adverse events (TRAEs) were increased alanine aminotransferase (13.8%), proteinuria (12.6%), rash (12.6%), and increased aspartate aminotransferase (10.3%). No TRAEs leading to death were reported.

Conclusion: SG001 demonstrated promising activity in patients with pretreated advanced solid tumors, especially those with PD-L1-positive NSCLC. The safety profile was well tolerated.

Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03852823.

© 2025 Fang et al.

In plain English

This was an open-label, single-arm, phase 1b trial of SG001, an anti-PD-1 antibody, run at 22 sites in China, 2020 to 2022. It did not study asbestos exposure. Eighty-seven previously treated patients with advanced cancers received 240 mg every two weeks: 33 with PD-L1-positive or other selected tumors (Cohort A), 24 with malignant mesothelioma (Cohort C), and 30 with non-small cell lung cancer (Cohort E). In the mesothelioma cohort, 3 of 24 patients (12.5%, 95% CI 2.7 to 32.4) had a confirmed partial response. Median progression-free survival there was 4.1 months (95% CI 1.3 to 9.4) and median overall survival 13.6 months (95% CI 3.7 to not available). Confirmed response rates were 39.4% (95% CI 22.9 to 57.9) in Cohort A and 16.7% (95% CI 5.6 to 34.7) in Cohort E. Overall, 78.1% had treatment-related side effects, 13.8% at grade 3 or higher. Fourteen patients had adverse events leading to death, none judged related to SG001. The authors concluded SG001 showed encouraging signs of activity and tolerable safety, particularly in lung cancer and malignant mesothelioma; they noted the small, single-arm design.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Open-label, multi-center, single-arm phase 1b dose-expansion clinical trial (three of five expansion cohorts reported), conducted September 28, 2020 to May 31, 2022 at 22 sites in China
• Who was studied: 87 patients with previously treated advanced solid tumors in China. Cohort A (n=33): tumors that were PD-L1 positive, dMMR/MSI-H and/or Epstein-Barr virus positive, most commonly NSCLC. Cohort C (n=24): histologically confirmed malignant mesothelioma, PD-L1-unselected, including malignant pleural mesothelioma and 3 peritoneal mesothelioma. Cohort E (n=30): non-small cell lung cancer without EGFR or ALK mutations, PD-L1-unselected.
• Exposure: Not an asbestos exposure study. The intervention was the anti-PD-1 antibody SG001, given as a 240 mg intravenous infusion every two weeks for up to 2 years or until disease progression, intolerable toxicity, or withdrawal.
• Main results:
  • Mesothelioma cohort (Cohort C, n=24): confirmed overall response rate 12.5% (95% CI 2.7 to 32.4), with 3 partial responses and 8 stable disease. Disease control rate 45.8% (95% CI 25.6 to 67.2).
  • Mesothelioma cohort (Cohort C): 8 of 24 patients had a progression-free survival event. Median progression-free survival was 4.1 months (95% CI 1.3 to 9.4).
  • Mesothelioma cohort (Cohort C): median overall survival 13.6 months (95% CI 3.7 to not available). The 18-month overall survival rate was 46.3% (95% CI 18.3 to 70.5).
  • Cohort A (n=33): confirmed overall response rate 39.4% (95% CI 22.9 to 57.9). All responses were partial responses (13/33).
  • Cohort A: median progression-free survival 9.6 months (95% CI 4.0 to 15.0).
  • Among the 16 Cohort A patients with PD-L1-positive NSCLC: confirmed overall response rate 43.8% (95% CI 19.8 to 70.1) and disease control rate 75% (95% CI 47.6 to 92.7).
  • Cohort E (NSCLC, n=30): 5 confirmed partial responses. Overall response rate 16.7% (95% CI 5.6 to 34.7) and disease control rate 63.3% (95% CI 43.9 to 80.1).
  • All 87 patients: treatment-related adverse events occurred in 78.1% (68/87).
  • All 87 patients: treatment-related adverse events of grade 3 or higher occurred in 12 of 87 patients (13.8%).
  • All 87 patients: adverse events leading to death occurred in 14 patients (16.1%). Investigators judged none of them related to SG001.
  • All 87 patients: immune-related adverse events occurred in 26 patients (29.9%).
• The authors' conclusion: The authors concluded that SG001 at 240 mg every two weeks showed encouraging signs of anti-tumor activity and a tolerable safety profile in advanced solid tumors, particularly in NSCLC and malignant mesothelioma.
• Limitations the authors state:
  • The trial was single-arm with a relatively small sample size.
  • The sample size was too small to draw firm conclusions about specific tumor types.
  • Subgroup analysis of the mesothelioma cohort by histology could not be done because histology information was insufficient.
  • The results need validation in larger randomized controlled trials with longer follow-up.

Topics

Medical terms in this study, explained in our Lexicon: Monoclonal Antibody, PD-L1, Microsatellite Instability (MSI-H), Mesothelioma, Non-Small Cell Lung Cancer, Disease Progression.

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