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Clinical Trial
. 2022 Dec 8:13:1074906.
doi: 10.3389/fimmu.2022.1074906. eCollection 2022.

Sintilimab plus autologous NK cells as second-line treatment for advanced non-small-cell lung cancer previous treated with platinum-containing chemotherapy

Lin Jia  1 , Naifei Chen  1 , Xiao Chen  1 , Chao Niu  1 , Ziling Liu  1 , Kewei Ma  1 , Nanya Wang  1 , Lei Yang  1 , Yuguang Zhao  1 , Wei Song  1 , Jin Lu  1 , Chen Chen  1 , Xiaofeng Cong  1 , Xu Wang  1 , Yinghui Xu  1 , Guozhen Cui  1 , Zengguang Liu  1 , Rongrong Chen  2 , Wei Li  1 , Jiuwei Cui  1
Affiliations
Clinical Trial

Sintilimab plus autologous NK cells as second-line treatment for advanced non-small-cell lung cancer previous treated with platinum-containing chemotherapy

Lin Jia et al. Front Immunol. .

Abstract

This pilot study (NCT03958097; https://www.clinicaltrials.gov/ct2/show/NCT03958097) was aimed to evaluate the efficacy and safety of PD-1 antibody combined autologous NK cells in the treatment of patients with stage IIIB/IIIC or IV non-small-cell lung cancer (NSCLC) who failed the first-line platinum-based chemotherapy. All patients received both sintilimab 200mg and 3×109 NK cells every 3 weeks. 20 patients were enrolled, median follow up time was 22.6 months. The median PFS was 11.6 months, ORR was 45%. Median OS was 17.7 months, 6-month OS rate and 12-month OS rate was 95.0% and 80.0%. Unexpected adverse events were not observed. 2 patients reported grade 3 adverse events (hypertriglyceridemia, neutropenia and increased creatine kinase). The autologous NK cells did not add extra adverse events to the ICI treatment. Autologous NK plus sintilimab showed promising antitumor activity and an acceptable safety profile in advanced driven-mutation negative NSCLC who failed on the first line treatment.

Keywords: NK cells; PD1 antibody; immune cell therapy; immunotherapy; non-small cell lung cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Progression-free survival in intention to treat population.
Figure 2
Figure 2
Best percentage change from baseline in target-lesion size.
Figure 3
Figure 3
Duration of response for patients with PR and CR.
Figure 4
Figure 4
PD-L1 expression in NK cells. (A) Representative flow cytometry analysis of PD-L1 expression baseline. Histogram plots show the isotype control staining profile (gray line) versus the specific antibody staining profile (red line). (B) PD-L1+ NK cell percentages and mean fluorescence intensity (MFI) indicate the PD-L1 expression in NK cells after treatment. (C) Representative flow cytometry analysis of PD-L1 expression after treatment. (D) PD-L1+ NK cell percentages and MFI indicate the PD-L1 expression in NK cells after treatment. ns, no significance.**p<0.01.*p<0.05. .
Figure 5
Figure 5
Ensemble diagram. (A) Study design. (B) Autologous PBMCs were collected by apheresis on D-14, then NK cells were isolated and cultured. 3×109 NK cells were divided into 3 days infusion during D1-D3, 200mg PD-1 antibody (sintilimab) was given on D1, 1 hour after NK cells infusion. NSCLC, non-small-cell lung cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; PFS, progression-free survival; ITT, intention to treatment; ORR, objective response rate; OS, overall survival; DoR, duration of response; DCR, disease control rate; CBR, clinical benefit rate; NK cells, Natural Killer cells; PBMC, peripheral blood mononuclear cells.
See this image and copyright information in PMC

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