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To evaluate the efficacy and safety of nintedanib plus docetaxel in patients with advanced adenocarcinoma non-small cell lung cancer (NSCLC) who progressed after chemotherapy and immune checkpoint inhibitor (ICI) therapy.VARGADO (NCT02392455) is an ongoing, prospective, non-interventional, real-world study of nintedanib plus docetaxel after first-line chemotherapy in the routine clinical treatment of patients with locally advanced, metastatic or locally recurrent adenocarcinoma NSCLC. Data were collected during routine visits. We report the results from cohort B (n = 80), who received third-line nintedanib plus docetaxel after first-line chemotherapy and second-line ICI therapy.The median duration of follow-up was 12.4 months. Median progression-free survival from initiation of third-line nintedanib plus docetaxel was 6.4 months (95% confidence interval 4.8, 7.3); median overall survival was 12.1 months (95% confidence interval 9.4, 13.5). The 1-year overall survival rate after initiation of third-line nintedanib plus docetaxel treatment (primary end point) was 52% (95% confidence interval 38.0%, 64.4%). Among 64 patients with a documented response, the objective response rate was 50% (n = 32; one complete response and 31 partial responses) and the disease control rate was 86% (n = 55). There were no new safety signals or unexpected toxicities. Among all treated patients, 74% (n = 59) experienced drug-related adverse events, most commonly (nintedanib-related/docetaxel-related) diarrhoea (34%/24%), a decreased white blood cell count (11%/19%) and nausea (13%/16%).Nintedanib plus docetaxel demonstrated a high response rate and disease stabilisation in the third-line setting after failure of prior chemotherapy and ICI treatment, with a manageable safety profile. These results suggest that nintedanib plus docetaxel represents an efficient treatment option after failure of prior ICIs. The ongoing VARGADO study provides valuable real-world data to inform clinical decision-making regarding treatment sequencing after chemotherapy and ICI failure in patients with adenocarcinoma NSCLC.

Background Catumaxomab, the approved therapy for treatment of malignant ascites, exerts its anti-tumor effects via T-cell-mediated lysis, antibody-dependent cell-mediated cytotoxicity, and phagocytosis via activation of FcγR-positive accessory cells. It has been reported that FcγR-polymorphisms influence the IgG binding capacity of the receptor and that ethnic groups may differ with respect to responsiveness of immune effector cells to antibody-based therapies. The present nonclinical study therefore investigated potential inter-ethnic differences (Caucasian vs. Japanese, Korean, Black African and Hispanic Donors) and FcγR-gene polymorphisms with regard to the potency of catumaxomab in vitro. Methods Blood samples of healthy subjects of different ethnic background (25 donors of Caucasian, Korean, Black African and Hispanic ethnicity and 15 Japanese donors) were collected for comparative analyses. PBMCs were purified from whole blood samples and used as effector cells evaluating catumaxomab-mediated cytotoxicity towards EpCAM+ tumor target cells (HCT-8; colon) in vitro. Furthermore, the samples were genotyped for FcγR IIa and FcγR IIIa gene polymorphisms by PCR. Results The comparative analysis of catumaxomab-mediated cytotoxicity obtained for the individual ethnic subgroups did not reveal major inter-ethnic differences although genetic polymorphisms for FcγR IIa/IIIa had been identified among donors. Even though a wider variability was observed among Caucasians, the potency range observed with immune effector cells of Japanese, Korean, Black African and Hispanic was found to be within the potency range observed for the Caucasian ethnicity. Conclusions No impact of ethnic background or FcγRIIa/IIIa polymorphism on the immune cell-mediated pharmacological activity of the trifunctional antibody catumaxomab could be identified in vitro. Therefore, it can be assumed that patients with a different ethnic background may also benefit from catumaxomab therapy as already demonstrated for Caucasian patients. Disclosure F. Marme: consultant for Fresenius Biotech GmbH. K. Hasegawa: financial support for clinical studies from Fresenius Biotech GmbH. H. Martinius: works for Fresenius Biotech GmbH. J. Atz: works for Fresenius Biotech GmbH. K. Fujiwara: financial support for clinical studies from Fresenius Biotech GmbH.