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Background Interleukin-1β (IL-1β) inhibition with canakinumab was associated with a significant reduction in the incidence of lung cancer and lung cancer mortality in pts with atherosclerosis in CANTOS trial. Inhibition of IL-1β driven inflammation may lead to a tumor microenvironment more susceptible to anti-PD-(L)1 therapies. Recent studies have shown that low levels of CRP at baseline or decreased levels over time correlated with improved responses to anti-PD-(L)1 agents, providing rationale for combining canakinumab and PEM. Trial design CANOPY-1 (NCT03631199) is a double-blind, randomized, placebo (Pb)-controlled, phase III trial to determine efficacy and safety of PEM + platinum-based Ctx ± canakinumab in untreated stage IIIB/IIIC-IV squamous and non-squamous NSCLC pts. It is a 2 part study- In part 1 (open-label safety run-in with 3 cohorts of ∼9 pts each), pts received canakinumab 200 mg s.c (Q3W) + PEM 200 mg i.v (Q3W) + platinum-based Ctx [Cohort A (non-squamous), carboplatin (CBCDA) + pemetrexed (PTX); Cohort B (non-squamous), cisplatin + PTX; Cohort C (squamous or non-squamous), CBCDA + paclitaxel]. In part 2 (with ∼600 pts), pts will be randomize to receive canakinumab/Pb + PEM + platinum-based Ctx (non-squamous, CBCDA or cisplatin + PTX; squamous, CBCDA + paclitaxel or nab-paclitaxel). PEM and platinum-based Ctx will be administered at their approved doses. Randomization (1:1) will be stratified by PD-L1 status, region, and histology. In both parts, pts will receive 4 cycles of induction therapy (canakinumab/Pb + PEM + Ctx) followed by maintenance therapy (PEM + canakinumab/Pb +/- PTX) until progressive disease. Primary objectives: confirm recommended phase 3 (RP3R) for canakinumab combination (part 1), compare PFS and OS between treatment arms (part 2). Secondary objectives (part 1 and 2): ORR, DCR, safety, PK and DOR. Part 1 is completed and part 2 is ongoing based on the confirmation of canakinumab 200 mg Q3W + PEM and platinum-doublet Ctx as RP3R. Clinical trial identification CACZ885U2301/NCT03631199. Legal entity responsible for the study Novartis. Funding Novartis. Disclosure D.S.W. Tan: Advisory / Consultancy: Novartis, Pfizer, AstraZeneca; Research grant / Funding (self): Novartis ; Advisory / Consultancy: Novartis; Research grant / Funding (self): Pfizer, AstraZeneca. T.M. Kim: Advisory / Consultancy: AstraZeneca, Novartis, Takeda, Sanofi, and Bayer ; Research grant / Funding (self): AstraZeneca-KHIDI outside this work. B.J. Solomon: Advisory / Consultancy: Roche/Genentech; AstraZeneca; Novartis; Pfizer; Merck; Bristol-Myers Squibb; Loxo Oncology; Gritstone Oncology; Honoraria (self): Roche/Genentech; AstraZeneca; Novartis; Pfizer; Merck; Bristol-Myers Squibb; Loxo Oncology; Gritstone Oncology. W.L. Tan: Travel / Accommodation / Expenses: Boehringer Ingelheim for WCLC in Toronto Sept 2018. S. Geater: Honoraria (self): AstraZeneca, Boehringer Ingelheim, Roche; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca, Boehringer Ingelheim, Roche, MSD; Travel / Accommodation / Expenses: AstraZeneca, Boehringer Ingelheim, Roche. G. De Castro Jr.: Honoraria (self): Bristol-Myers Squibb; Merck Serono Serbia; MSD; Advisory / Consultancy: Bristol-Myers Squibb; MSD; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Merck Serono Serbia; MSD; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Merck Serono Serbia; MSD. A. Greystoke: Speaker Bureau / Expert testimony: Novartis, AstraZeneca, Boehringer Ingelheim, BMS, MSD, Takeda, Pfizer; Advisory / Consultancy: Novartis, AstraZeneca, Boehringer Ingelheim, BMS, MSD, Takeda, Pfizer. E. Felip: Advisory / Consultancy: AbbVie; AstraZeneca; Blueprint Medicines; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Guardant Health; Lilly; Merck KGaA; Merck Sharp & Dohme; Novartis; Pfizer; Roche; Takeda; Speaker Bureau / Expert testimony: AbbVie; AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Lilly; Merck KGaA; Merck Sharp & Dohme; Novartis; Pfizer; Roche; Takeda; Research grant / Funding (self): EMD Serono (Inst); Fundación Merck Salud (Inst). B.E. Johnson: Advisory / Consultancy: Novartis Steering Committee and Array Biopharma Steering Committee; Research grant / Funding (self): Research Grants from Novartis and Cannon Medical Imaging. A-L. Louveau: Full / Part-time employment: Novartis. V.Q. Passos: Full / Part-time employment: Novartis. B.C. Cho: Shareholder / Stockholder / Stock options: TheraCanVac Inc; Honoraria (self): AstraZeneca; Bayer; Champions Oncology; Dizal Pharma; Dong-A ST; Janssen; MOGAM Institute; MSD; Novartis; Ono Pharmaceutical; Yuhan; Advisory / Consultancy: AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Janssen; Lilly; MSD; Novartis; Ono Pharmaceutical; Pfizer; Roche; Takeda; Yuhan; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (self): AstraZeneca; Bayer; Champions Oncology; Dizal Pharma; Dong-A ST; Janssen; MOGAM Institute; MSD; Novartis; Ono Pharmaceutical; Yuhan; Licensing / Royalties: Champions Oncology. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Genomic rearrangements involving neurotrophic tropomyosin receptor kinase 1, 2, or 3 (NTRK1/2/3) result in constitutively active tropomyosin receptor kinase (TRK) fusion proteins that are oncogenic drivers in multiple pediatric and adult cancers. Larotrectinib is a selective TRK inhibitor approved by the US Food and Drug Administration in 2018 for the treatment of TRK fusion cancer based on a primary analysis in 55 patients from 3 clinical trials [Drilon et al. NEJM 2018]. Here, we report median duration of response (DOR) data in the primary cohort and updated data in an expanded cohort of 159 patients with TRK fusion cancer treated with larotrectinib, with 153 (55 primary + 98 supplemental) evaluable for efficacy. Methods Patients with TRK fusion cancer detected by local molecular profiling were treated with larotrectinib across 3 studies (NCT02122913, NCT02637687, NCT02576431). Disease status was assessed by investigators using RECIST 1.1. Data cut-off was February 19, 2019. Results In the primary cohort of 55 patients with a median follow-up of 26 months, the median DOR in 44 patients with complete or partial responses was 35.2 months (95% CI 21.2–not evaluable [NE]), with 17 progression events and 27 responses ongoing (range 1.6–44 months). Median progression-free survival in the primary cohort was 25.8 months (95% CI 9.9–NE), with 27 patients having progressed. In the expanded combined dataset, the most common tumor types included soft tissue sarcoma (n = 36), infantile fibrosarcoma (n = 29), thyroid carcinoma (n = 26), salivary gland carcinoma (n = 21), and lung cancer (n = 12). Median age was 43 years, ranging from < 1 month to 84 years; 33% < 18 years. The overall response rate was 79% (95% CI 72–85), with complete responses in 16%. Adverse events were mostly grade 1–2; 13% of patients had a grade 3–4 event related to larotrectinib. Only one patient discontinued due to an adverse event related to larotrectinib. Conclusions These data confirm the marked tissue-agnostic efficacy and long durability of response in patients with TRK fusion cancer treated with larotrectinib. Larotrectinib demonstrated a favorable long-term safety profile. Screening patients for NTRK gene fusions should be considered. Clinical trial identification NCT02122913, NCT02637687, NCT02576431. Legal entity responsible for the study Bayer. Funding Bayer. Disclosure F. Doz: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (self): Celgene; Advisory / Consultancy: Bayer; Advisory / Consultancy: Loxo Oncology; Advisory / Consultancy: Servier. L. Mascarenhas: Speaker Bureau / Expert testimony: Bayer. J. Berlin: Research grant / Funding (institution): PsiOxus; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): AbbVie (pharamcyclics); Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): FivePrime; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Macrogenics; Honoraria (self): Nestle; Advisory / Consultancy: Rafeal; Advisory / Consultancy: Seattle Genetics; Honoraria (self): Eisai; Advisory / Consultancy: Taiho; Advisory / Consultancy: Armo. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines. [ABSTRACT FROM AUTHOR]

Background There is an expanding list of therapeutically relevant biomarkers for NSCLC and effective molecular profiling is paramount. We sought to comprehensively and prospectively evaluate the molecular epidemiology of NSCLC in Asia and ascertain the extent of access to relevant therapies. The study is being conducted by the Asian Thoracic Oncology Research Group (ATORG) – an academic co-operative lung cancer trials group in Asia. Methods ATORG-001 is a prospective, multi-centre study of NSCLC patients (pts) throughout Asia. Eligible pts must have good performance status (ECOG ≤2), adequate organ function and ≤3 prior lines of cytotoxic chemotherapy. Archival tissue specimens are sent to a central laboratory in Singapore (Singapore General Hospital) for profiling, consisting of NGS with the Oncomine Focus Assay (52 gene panel including fusions) and PD-L1 immunohistochemistry. Results are returned to investigators in a clinically relevant timeframe. Baseline demographics, pre-existing molecular profile and prior treatment details are collected. Treatment and pt outcomes are followed for 2 years. Recruitment commenced in Jan 2019 in 3 sites (National Cancer Centre Singapore, Chinese University of Hong Kong, University Malaya Medical Centre). We report an interim analysis for the first 27 of a planned 500 pts. Results As of 01 Jul 2019, 27 pts have enrolled with median age 67 yrs (range 46-79), 59% male, 81% adenocarcinoma, 52% stage IV, 37% non-smokers, median lines of prior therapy 1 (range 0-6) and 85% with no known oncogenic driver. Pre-existing mutation status was known in 89% for EGFR and 63% for ALK. Median turnaround time from tissue acquisition to profiling results was 22 days (range 15-74). New alterations were most common in KRAS (19%), MYC (15%), CDK4 (7%) and ERBB2 (7%). Potentially actionable new alterations were found in 7 (26%) pts, including KRAS G12C mutation (7%), BRAF G469A mutation (4%), ERBB2 exon 20 insertion (4%), ERBB2 amplification (4%), FGFR2 amplification (4%) and MET exon 14 skipping mutation (4%). Conclusions Enrolment is ongoing with additional sites and countries planned to comprehensively evaluate the molecular epidemiology of NSCLC in Asia. Legal entity responsible for the study Asian Thoracic Oncology Research Group. Funding Asian Thoracic Oncology Research Group, Novartis. Disclosure A.C. Tan: Travel / Accommodation / Expenses: ASLAN Pharmaceuticals. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]