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Background The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumor immunity and resistance to multiple therapies including CPIs. Bemcentinib is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy in the pre-clinical setting. Methods This PhII trial enrolled 48 advanced lung adenocarcinoma pts with progression on or after 1 prior line of PLT-based chemotherapy. Primary endpoint was ORR according to RECIST 1.1. Additional endpoints included efficacy according to biomarker expression, DCR, PFS, OS and safety. Tumor biopsies were analyzed for AXL by IHC, and PD-L1 expression (22C3 pharmDx). Additional biomarker analysis was also performed. Results In May 2019, Cohort A was fully recruited: median age 65 (range 39-82) yrs, 61% male, 76% smokers or ex-smokers. Pts had completed a median of 3 treatment cycles. 15 pts were ongoing. Out of 32 pts with available PD-L1, 17 (53%) had TPS 50%. Out of 33 patients with available AXL IHC, 19 (58%) expressed AXL on their tumors. Among pts who had at least 1 evaluable post-baseline scan: ORR was 10/38 (26%) overall, 6/16 (38%) in AXL positive pts (compared to 2/13 (15%) in AXL negative pts), and 7/30 (23%) in pts with TPS 0-49%. 12-mo OS was 54% overall (2 pts lost to follow up). mOS overall was 12.2 mos (95% CI 6.2 – NR). In pts with AXL positive tumors, mOS was 12.2 mos (2.0 – NR) and in AXL negative 12.7 mos (5.6 – NR). In PD-L1 negative pts, mOS was 12.4 mos (5.6-NR). Most common TRAEs (occurring in > 10% of pts) were transaminase increases (35%), asthenia/fatigue (30%), diarrhea (26%), nausea (13%), anemia (11%), and decreased appetite (11%). All cases of transaminase increase were reversible and resolved. 13 pts (28%) had TRAEs grade > 3, all of which were resolved or resolving at the time of writing. No treatment-related deaths were reported. Conclusions The combination of bemcentinib and pembro was well tolerated and showed promising efficacy in previously treated IO-naive NSCLC pts, particularly in those with AXL positive disease, including PD-L1 negative pts. mOS of > 12 mos is favorable compared with historical references in the NSCLC second-line setting. Clinical trial identification NCT03184571. Legal entity responsible for the study BerGenBio ASA. Funding BerGenBio ASA. Disclosure J.M. Trigo Perez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Blueprint Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Medscape; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck KGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Touchtime. A. Helland: Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: PierreFabre; Speaker Bureau / Expert testimony: Pfizer. E. Arriola: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. R. Garcia Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche/Genentech; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. J. Spicer: Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): Bayer; Honoraria (institution), Research grant / Funding (institution): BerGenBio ASA; Honoraria (institution), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Research grant / Funding (institution): BMS; Honoraria (institution), Research grant / Funding (institution): Curis; Honoraria (institution), Research grant / Funding (institution): Genmab; Honoraria (institution), Research grant / Funding (institution): Roche; Honoraria (institution), Research grant / Funding (institution): Starpharma; Honoraria (institution), Research grant / Funding (institution): Taiho; Shareholder / Stockholder / Stock options: IGEM Therapeutics. R.J. Holt: Full / Part-time employment: BerGenBio ASA. J.B. Lorens: Leadership role, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Full / Part-time employment: BerGenBio ASA. M. Shoaib: Advisory / Consultancy, Full / Part-time employment: BerGenBio ASA. A. Siddiqui: Advisory / Consultancy, Full / Part-time employment: BerGenBio ASA. E.V. Schmidt: Full / Part-time employment: Merck Sharp & Dome. M.J. Chisamore: Full / Part-time employment: Merck Sharp & Dome. M.G. Krebs: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Achilles Therapeutics; Advisory / Consultancy: Octimet; Advisory / Consultancy: Janssen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: BerGenBio ASA. All other authors have declared no conflicts of interest.

Background CT-RT is the standard treatment for unresectable LA-NSCLC. P plus vinorelbine is widely used. Metronomic CT is a frequent administration of low doses of CT. mOV has shown good efficacy and improved safety, and could improve the RT effect. Our goal is to evaluate the efficacy and safety of P-mOV with radical RT in patients (pts) with LA-NSCLC. Methods Pts aged 18-75 years with histologically proven untreated and unresectable LA-NSCLC, adequate bone marrow, hepatic & renal function, ECOG PS0-1, received P 80mg/m2 D1 every 3 weeks combined with mOV 50mg/day on days D1, 3 & 5/weekly, 2 cycles (cy) as induction; patients without progression received 2 more cy of P at the same dose with mOV 30mg/day on D1, 3 & 5/weekly, concurrently with RT (66Gy in 6.5weeks). Primary endpoint was progression-free survival (PFS) by RECIST v1.1; secondary endpoints were: overall response rate (ORR), disease control rate (DCR), overall survival and safety profile. To guarantee an overall type-1 α error no greater than 0.05 and a type II (β) error 0.1 for PFS, a sample size of 67 pts was planned. Results Sixty-seven pts were recruited in 17 Spanish sites from 04/2016 to 06/2017. One of them didn’t meet all the inclusion criteria. We analyzed 66 pts included. Pt characteristics: Male 77.3%; median age 62 (range 33-75); PS 0/1 52/49%; smokers 53%; adenocarcinoma/squamous 43.9/42.4%; stage IIIA/B 42.4/57.6%. Only 32.3% of pts presented any grade 3-4 adverse event, including: neutropenia 20.0%; anemia 4.6%; febrile neutropenia 6.2%; esophagitis 3.1%; pneumonitis 1.5%. There were two deaths non-related to the treatment, during this period. Fifty-one pts have completed the treatment. ORR: 67.7%. DCR: 84.6%. With a median follow-up of 22.3 months (range 1.1-34.9), the median PFS is 11.5 months (CI95%; 9.9-15,4). Conclusions mOV-P with RT is as effective as the standard administration of vinorelbine, improving its safety profile. Clinical trial identification EudraCT 2015-003312-21. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Pierre Fabre. Disclosure All authors have declared no conflicts of interest.

Background Target therapy guide by biomarkers have become the standard of care for patients with lung cancer (LC). So, identify those molecular alterations is one of the most important care needs nowdays. Our objective was to know the implementation degree of these tests in a large cohort of patients in Spain using the Thoracic Tumor Registry (TTR) of the Grupo Espanol de Cancer de Pulmon (Spanish Lung Cancer Group). Methods The TTR is an observational cohort multicenter study of LC in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating institute. The registry was approved by the Spanish Drug Agency as a non-post-authorization, non-interventional study. We analyzed the molecular biomarkers considering all stages of LC. Results A total of 7,872 patients from 58 Spanish centers were enrolled between August 2016 to December 2018. The most frequent screened molecular test was the EGFR mutations, it was performed in 4,456 patients (67.5%). The proportion of biomarker evaluation has varied over time, ranging from 57.9% prior to 2012 up to 73.7% in 2017. The molecular assessment of some biomarkers reached 81.4% of these patients, with some differences between Regional Communities, regarding the molecular tests performed. Three thousand four hundred forty-six (3,446) patients (52.2%) had a stage IV at diagnosis. There was performed some biomarker test in 92% of the 2570 patients with stage IV and non-squamous histology. In those stage IV non-squamous patients, the EGFR and ALK test were performed in 92% and 79% respectively but 2 years ago ALK test was done only in 40% of the patients. ROS1 was studied in 20% of the cases. Conclusions Although no national plan exists for molecular biomarker analysis in Spain, the implementation of biomarkers tests in all the hospitals that contribute to the TTR is high. The increase in the ALK analysis in the last period is relevant. As we have some regional differences, it is important to understand the causes to improve them. Clinical trial identification NCT02941458. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Novartis, Merck Sharp and Dohme, Lilly. Disclosure All authors have declared no conflicts of interest.

Background Tobacco use, mainly as cigarette smoking, is the leading cause of lung cancer. Eighty-five percent of LC occur in smokers. Understanding the Spanish smoking habits allows the government to design health care policies against this consumption. To do so, the Grupo Espanol de Cancer de Pulmon (Spanish Lung Cancer Group) made this analysis within the context of the Thoracic Tumor Registry (TTR). Methods The TTR is an observational cohort multicenter study in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating site. The registry was approved by the Spanish Drug Agency, as a non-post-authorization, non-interventional study. Results Data have been collected from 6,600 LC from 58 different hospital sites across Spain. 12% (866 p) were non-smokers, 46% (3,039 p) were former smokers and 39% (2,611 p) were smokers. There were significant differences by gender, more women were non-smokers (37 % vs. 45% in males), meanwhile more former smokers were male (53.4% vs. 27.9% in women) (p-valor Conclusions Tobacco use is the leading cause of LC in Spain accounting 85% of the cases. Consumption has increased in both genders, but specially in women, in our country among lung cancer patients. Tobacco cessation campaigns, especially in women, should be a priority in western countries, like Spain, and it has to be adapted to regional differences in tobacco use. Clinical trial identification NCT02941458. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Novartis, MSD, Lilly. Disclosure M. Provencio: Advisory / Consultancy: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Background: Thirty percent to ninety percent of cancer patients suffer from pain, including neuropathic pain (NP), which results in great burden for cancer patients. Thus, it was of great interest to determine NP prevalence in cancer patients in Spain, to raise awareness of the condition, and aiming to improve management of cancer NP. Patients and methods: A 1-month follow-up prospective epidemiological multicenter study was conducted to assess prevalence and management of NP in Spanish oncologic units. The first 10 cancer patients at each unit diagnosed with NP by the validated Douleur Neuropathique 4 questionnaire (DN4) were recruited. Results: Of 8615 screened patients, 2567 (30%) suffered from pain. From these, 33% had NP according to investigators and 19% according to DN4 test. Three hundred and sixty-six patients (mean age 62.6 years; 61.2% male) were recruited. Pain decrease at 1 month was greater in patients with metastases (P < 0.01) and depended on treatment (P < 0.05), with 'oxycodone' showing 50.4% pain relief. Conclusions: NP prevalence in cancer pain is 33%. DN4 reports only about half the cancer NP cases diagnosed by clinicians. Pharmaceutical treatment of cancer pain, including NP, has a greater effect in patients with metastases and seems to depend on the specific treatment used.