Abstract
The randomized, double-blinded, multi-center, phase III GEMSTONE-302 (NCT03789604) study evaluated the efficacy and safety of sugemalimab versus placebo in combination with chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (NSCLC). In this study, 479 treatment-naive patients with stage IV squamous or non-squamous NSCLC without known EGFR sensitizing mutations, ALK, ROS1 or RET fusions were randomized (2:1) to receive 1,200 mg of sugemalimab (n = 320) or placebo (n = 159) every 3 weeks in combination with platinum-based chemotherapy for up to four cycles, followed by maintenance therapy with sugemalimab or placebo for squamous NSCLC and sugemalimab or placebo plus pemetrexed for non-squamous NSCLC. Placebo-treated patients could cross over to receive sugemalimab monotherapy on disease progression. The primary endpoint was investigator-assessed progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and objective response rate. Sugemalimab plus chemotherapy has demonstrated significant PFS prolongation in the primary analysis as reported previously. As of 22 November 2021, the prespecified interim OS analysis showed significant improvement with the addition of sugemalimab to chemotherapy (median OS = 25.4 versus 16.9 months; hazard ratio = 0.65; 95% confidence interval = 0.50–0.84; P = 0.0008). Sugemalimab plus chemotherapy provided superior PFS and OS compared to placebo plus chemotherapy, supporting the use of sugemalimab as a first-line treatment option for metastatic NSCLC.
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Data availability
The data supporting the findings of this study are not publicly available due to restrictions regarding patient privacy but are available upon reasonable request. Data will be available to evaluate this paper, verify its contents and for research use. All requests for clinical data will be reviewed by the sponsor (CStone Pharmaceuticals) to verify if the request is subject to any intellectual property or confidentiality obligations. Source data are provided with this paper.
Change history
05 January 2024
A Correction to this paper has been published: https://doi.org/10.1038/s43018-023-00719-4
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Acknowledgements
The study was supported by CStone Pharmaceuticals. The funders had a role in the conceptualization, study design, data collection, data analysis and manuscript preparation. The authors thank all patients and their families for participating in the study, as well as the study investigators and other staff. We also thank S. Chi from CStone Pharmaceuticals and X. Wang from IQVIA (funded by CStone Pharmaceuticals) for their assistance with the statistical analysis. Medical writing assistance was provided by J. Kolston and S. Neville of Parexel (funded by CStone Pharmaceuticals), and M. Zhao and A. Wu of CStone Pharmaceuticals.
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Contributions
C.Z., Z.W., Y.L., Z.M., H.S., J.W. and J.Y. provided substantial contributions to the conception and design of the study. C.Z., Z.W., M.S., L.C., Z.M., R.W., Y.Y., W.Y., S.S., J. Che, W.Z., J. Cu, X.C., Y. Lu, H.S., C.H., J. Liu, Y. Liu, M.W., X.L., P.S., Y.S., J.Z., J. Li, K.G., C.W., H.Z., Y.Z. and C.L. enrolled and treated the patients. H.W. carried out the statistical analyses and generated the data. C.Z., J.W., R.C., M.Q. and J.Y. analyzed and interpreted the data. C.Z., J.W., R.C., M.Q. and J.Y. drafted the manuscript and provided critical revision of the manuscript. C.Z., J.W., R.C., M.Q. and H.W. verified the data. All authors had full access to the study data, reviewed the data, contributed to the development of the manuscript, approved the final version and had final responsibility for the decision to submit it for publication.
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Competing interests
C.Z. reports speaker honoraria from CStone Pharmaceuticals during the course of this study and, outside this study, reports speaker honoraria from Lilly China, Sanofi, Boehringer Ingelheim, Roche, MSD, Qilu Pharmaceutical, Jiangsu Hengrui Therapeutics, Innovent Bio, Luye Pharma Group, TopAlliance Biosciences and Amoy Diagnostics; he is an adviser for Innovent Bio, Jiangsu Hengrui Therapeutics, Qilu Pharmaceutical and TopAlliance Biosciences. J.W., R.C., M.Q., H.W. and J.Y. are paid employees of CStone Pharmaceuticals. J.W. and J.Y. declare stock ownership in the company. The other authors declare no competing interests.
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Extended data
Extended Data Fig. 1 Supplementary progression-free survival in patients in the double-blind intention-to-treat population grouped according to tumor PD-L1 expression level.
a, All patients. Sugemalimab group, N = 320 patients; Placebo group, N = 159 patients. b, Patients with PD-L1 ≥ 1%. Sugemalimab group, N = 196 patients; Placebo group, N = 96 patients.c, Patients with PD-L1 < 1%. Sugemalimab group, N = 124 patients; Placebo group, N = 63 patients. d, Patients with PD-L1 1–49%. Sugemalimab group, N = 92 patients; Placebo group, N = 48 patients.e, Patients with PD-L1 ≥ 50%. Sugemalimab group, N = 104 patients; Placebo group, N = 47 patients. CI, confidence interval; HR, hazard ratio; PD-L1, programmed death ligand 1.
Extended Data Fig. 2 Waterfall plots of best percentage change from baseline in sum of diameters assessed by investigator in double-blind phase.
a, Sugemalimab plus platinum-based chemotherapy. N = 203 patients. b, Placebo plus platinum-based chemotherapy. N = 64 patients.
Extended Data Fig. 3 Duration of response (double-blind ITT population).
Kaplan–Meier estimates of duration of response (investigator assessed) in patients with metastatic NSCLC without known sensitising mutations, treated with sugemalimab plus chemotherapy (sugemalimab group, N = 203 patients) or placebo plus chemotherapy (placebo group, N = 64 patients). CI, confidence interval; NSCLC, non-small-cell lung cancer.
Extended Data Fig. 4 progression-free survival and overall survival in crossover arm.
N = 45 patients in crossover arm. a, progression-free survival and b, overall survival in patients with metastatic NSCLC without known sensitizing mutations who were treated with 2 L sugemalimab monotherapy in the crossover arm. 2 L, second-line; CI, confidence interval; NSCLC, non-small cell lung cancer.
Supplementary information
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Zhou, C., Wang, Z., Sun, M. et al. Interim survival analysis of the randomized phase III GEMSTONE-302 trial: sugemalimab or placebo plus chemotherapy as first-line treatment for metastatic NSCLC. Nat Cancer 4, 860–871 (2023). https://doi.org/10.1038/s43018-023-00578-z
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DOI: https://doi.org/10.1038/s43018-023-00578-z
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