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Clinical Trial
. 2024 Feb 19;15(1):1512.
doi: 10.1038/s41467-024-45769-z.

Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial

Mina Zhang  1 , Guowei Zhang  1 , Yuanyuan Niu  1 , Guifang Zhang  2 , Yinghua Ji  3 , Xiangtao Yan  1 , Xiaojuan Zhang  1 , Qichuan Wang  4 , Xiaohui Jing  5 , Junsheng Wang  6 , Zhiyong Ma  1 , Huijuan Wang  7
Affiliations
Clinical Trial

Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial

Mina Zhang et al. Nat Commun. .

Abstract

This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Flow chart of the clinical trial (patient flow chart).
AEs adverse events, PD disease progression.
Fig. 2
Fig. 2. Survival outcomes and tumor responses.
Progression-free survival (a), duration of response (b), overall survival (c) curves for the efficacy analysis set (n = 44), and (d) waterfall plot of best percentage change from baseline (n = 44). Patients 06001 and 02003 experienced PR only once, and were subsequently evaluated as PD. The optimal overall efficacy was evaluated as PD. For patient 01029, the efficacy evaluation was SD → SD → PR → PD, with only one optimal response of PR. the optimal overall efficacy evaluation was SD. CI confidence interval, DOR duration of response, NE not evaluable, OS overall survival, PD disease progression, PFS progression free survival, PR partial response, SD stable disease. Source data are provided in the Source Data file.
Fig. 3
Fig. 3. Exploratory biomarker analyses.
a The top-ranked mutated genes in the studied cohort with colors representing different types of mutations (n = 26). b Kaplan–Meier survival curves depicting the PFS of patients carrying any of the BRAC2, BRINP2, FBXW7, KIT, RB1 mutations or wild type. c The best response of patients with ctDNA clearance at C1 or C2 and those without ctDNA clearance including baseline clearance patients. d The best response of patients with ctDNA clearance at C1 or C2 and those without ctDNA clearance, excluding baseline clearance patients. e Kaplan–Meier survival curves depicting the PFS times of patients with ctDNA clearance or with ctDNA uncleared at C2 including baseline clearance patients. f Kaplan–Meier survival curves depicting the PFS times of patients with or without ctDNA clearance at C2 excluding baseline clearance patients. g Correlation between ctDNA dynamics and the clinical response. b, e, f p values were calculated using the one-sided log-rank test at a significance level of 0.05. c–d Two-sided Fisher’s exact test. BRCA2 breast cancer gene 2, BRINP3 BMP/Retinoic Acid Inducible Neural Specific 3, CI confidence interval, ctDNA circulating tumor DNA, FBXW7 F-box/WD repeat-containing protein 7, HR hazard ratio, KIT tyrosine-protein kinase KIT, Mut mutation, PFS progression-free survival, RB1 retinoblastoma 1, Wt wild type. Source data are provided in the Source Data file.
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