Chugai Pharma Research Articles

519P - Initial results of lung cancer genomic screening project for individualized medicine in Asia: LC-SCRUM-Asia

BackgroundLC-SCRUM was established in 2013 to screen target genes in lung cancer to advance the development of new molecular targeted drugs and diagnostics. To date, with the cooperation of over 200 institutions across Japan, LC-SCRUM has performed genomic analysis of over 7000 lung cancer patients. Since Mar 2019, LC-SCRUM has expanded to Taiwan as genomic screening infrastructure with the cooperation of Asian countries. Here, we report initial results of Asian international genomic screening, LC-SCRUM-Asia. MethodsTumor samples of non-small cell lung cancer patients were analyzed for oncogenic alterations using targeted next-generation sequencing (NGS) with Oncomine Comprehensive Assay. The analysis was performed as central test at CLIA lab in Japan. ResultsAs of May 31th in 2019, the LC-SCRUM-Asia has the participation of 5 institutions in Taiwan and 161 in Japan. For the first 2 month, a total of 477 patients (23 from Taiwan and 454 from Japan) were enrolled in this study. Median age were 68 years (range, 45-84) in Taiwan cohort and 67 (28-87) in Japan. In Taiwan 65% of patients were women, 70% adenocarcinoma and 70% non-smoker, and in Japan 37% of patients were women, 79% adenocarcinoma and 29% non-smoker, respectively. Of 13 analyzable patients in Taiwan, targeted NGS showed that 9 (69%) had at least one targetable oncogenic alterations, including 4 EGFR mut, 2 KRAS mut, 2 ALK fusinos and 1 RET fusions plus EGFR mut. Of 423 patients in Japan, 196 (46%) had at least one targetable oncogenic alterations. Oncogenic alterations commonly found were EGFR mut (19%), KRAS mut (13%), ALK fusions (2%), RET fusions (1%) and others in Japan. ConclusionsAsian international genomic screening can be implemented between Taiwan and Japan settings. LC-SCRUM-Asia will contribute to further development of precision medicine for lung cancer patients in Asia. Updated results will be presented at the meeting. Legal entity responsible for the studyLC-SCRUM-Asia. FundingAstraZeneca, Ignyta, Kyowa Hakko Kirin, Daiichi Sankyo, Eisai, Taiho, Takeda, Merck Serono, Novartis, MSD, Pfizer, Lilly, Bristol-Myers Squibb, Chugai, Boehringer Ingelheim, Astellas, LOXO, Janssen, Thermo Fisher Scientific, Ono. DisclosureC-H.S. Kuo: Honoraria (self): AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): ONO Pharma; Honoraria (self), Advisory / Consultancy: Merck; Advisory / Consultancy: Chugai; Advisory / Consultancy: Takeda. K. Yoh: Honoraria (self): Chugai; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): MSD; Honoraria (self): Novartis. Y. Zenke: Honoraria (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Chugai; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self): Taiho; Honoraria (self): Ono pharmaceutical. S. Matsumoto: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Chugai Pharma. K. Goto: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): LOXO; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Thermo Fisher Scientific; Research grant / Funding (institution): Ono. All other authors have declared no conflicts of interest.

LBA2 - TATTON expansion cohorts: A phase Ib study of osimertinib plus savolitinib in patients (pts) with EGFR-mutant, MET-positive NSCLC following disease progression on a prior EGFR-TKI

BackgroundPreliminary data from TATTON (NCT02143466, a multi-arm, multi-drug combination study) suggested that adding savolitinib (AZD6094, HMPL-504, volitinib), a potent and highly selective MET TKI, to osimertinib, a 3rd generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), which selectively inhibits EGFR TKI sensitising (EGFRm) and T790M resistance mutations, may overcome MET-driven resistance to EGFR TKIs. We present updated data from TATTON Part B and data from Part D, for the first time. MethodsPts were ≥18 years (Japan ≥20 years), mainly Asian, with locally advanced/metastatic, MET-positive, EGFRm NSCLC and disease progression on prior therapy. Pts enrolled based on MET status by local fluorescent in-situ hybridisation (MET gene copy ≥5 or MET/CEP7 ratio ≥2), next-generation sequencing or immunohistochemistry (+3 in ≥ 50% of tumour cells), with retrospective central confirmation. Pts in Part B received osimertinib 80 mg + savolitinib 600 mg or 300 mg orally (PO) once daily (QD). Pts in Part D received osimertinib 80 mg + savolitinib 300 mg PO QD, were T790M negative and had received no prior 3rd generation EGFR TKI. Primary endpoints: safety and tolerability; secondary endpoints included objective response rate and progression-free survival. ResultsIn Parts B (N = 138) and D (N = 42); Grade ≥3 AEs reported by 57% and 38%, respectively; serious AEs reported by 45% and 26%, respectively. AEs possibly related to treatment, led to discontinuation of savolitinib in 38 (28%) vs 9 (21%) and osimertinib in 14 (10%) vs 2 (5%), for Parts B and D, respectively. Efficacy data: Table.TableLBA2 Efficacy endpointsTablePart BPart DEndpointPreviously treated with a 3G EGFR TKINo prior 3G EGFR TKI, T790M-negativeNo prior 3G EGFR TKI, T790M-positiveTotalNo prior 3G EGFR TKI, T790M-negativeBest responsen = 69n = 51n = 18n = 138n = 36*ORR†, n (%) [95% CI]21 (30) [20–43]33 (65) [50–78]12 (67) [41–87]66 (48) [39–56]23 (64) [46–79]PFSn = 69n = 51n = 18n = 138n = 42Median PFS, months5·49·011·07·69·1[95% CI][4·1–8·0][5·5–11·9][4·0–NR][5·5–9·2][5·4–12·9]Total events, n (%)43 (62)33 (65)10 (56)86 (62)17 (40)*Best response data are for patients who had an opportunity to have two follow-up scans.†All confirmed responses were partial response. ConclusionsOur results support that osimertinib + savolitinib may overcome MET-driven resistance to EGFR TKIs, and warrant further exploration of the osimertinib 80 mg + savolitinib 300 mg combination in the SAVANNAH (NCT03778229) and ORCHARD (NCT03944772) studies. Clinical trial identificationNCT02143466. Editorial acknowledgementLaura Crocker, BMedSci, of iMed Comms, an Ashfield Company, funded by AstraZeneca. Legal entity responsible for the studyAstraZeneca. FundingAstraZeneca. DisclosureJ. Han: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Research grant / Funding (self): ONO; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Takeda. L.V. Sequist: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Janssen; Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Merrimack Pharmaceuticals; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): LOXO; Honoraria (self), Research grant / Funding (institution): Blueprint Medicines; Honoraria (self), Research grant / Funding (institution): Genentech. M. Ahn: Honoraria (self), Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD, Ono Pharmaceutical, Roche; Advisory / Consultancy: Takeda, Alpha Pharmaceutical. B.C. Cho: Research grant / Funding (institution): Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono Pharmaceutical, Dizal Pharma, MSD; Advisory / Consultancy: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Ono Pharmaceutical, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, and MSD; Shareholder / Stockholder / Stock options: TheraCanVac Inc, Gencurix Inc, Bridgebio Therapeutics; Licensing / Royalties, Patent with royalties paid: Champions Oncology. H. Yu: Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): AstraZeneca, Lilly, Pfizer, Daiichi, Novartis, Astellas. S. Kim: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. J.C. Yang: Honoraria (self): AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai, MSD, Pfizer, Novartis, Bristol-Myers Squibb, Ono Pharmaceuticals; Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, Bristol-Myers Squibb, Ono Pharmaceuticals, Daiichi Sankyo, Hansoh, Takeda, Blueprint. M. Cantarini: Shareholder / Stockholder / Stock options, Full / Part-time employment, Full time Contractor: AstraZeneca. R.B. Verheijen: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: Aduro Biotech. A. Mellemgaard: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Frewer: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. X. Ou: Full / Part-time employment, Full time Contractor: AstraZeneca. G. Oxnard: Honoraria (self): Chugai Pharma, Bio-Rad, Sysmex, Guardant Health, Foundation Medicine; Advisory / Consultancy: AstraZeneca, Inviata, Takeda, Loxo, Ignyta, DropWorks, GRAIL, Illumina, Janssen; Licensing / Royalties, Patent pending: DFCI.

486P - Phase II study of low-dose afatinib maintenance treatment for patients with EGFR-mutated non-small cell lung cancer (NJLCG1601)

BackgroundAfatinib is a 2nd generation EGFR-TKI and has been a standard first line treatment for patients (pts) with advanced NSCLC with EGFR mutations. Afatinib has good efficiency, whereas afatinib has severe adverse events (AEs) and often lead to discontinuation of treatment or a dose reduction. NJLCG1601 was conducted to evaluate the efficacy of low-dose afatinib maintenance treatment. MethodsEGFR-TKI-naïve stage III / IV / recurrent NSCLC pts harboring EGFR mutations (exon 19 deletion or exon 21 L858R or minor mutation) were enrolled. Pts received afatinib 40mg orally once a day. When prescribed AEs (grade ≧ 2 in CACAE ver 4.0) or unacceptable AEs occurred, a dose of afatinib was reduced from 40mg to 30mg, 30mg to 20mg. The treatment was continued until disease progression, occurrence of intolerable severe AEs, or withdrawal of consent. The primary endpoint was 1-year progression free survival (PFS) rate. Secondary endpoints were PFS, overall response rate (ORR), the incidence of AEs, and the incidence of grade ≧ 3 AEs. Assuming a threshold 1-year PFS rate of 42% and an expected 1-year PFS rate of 63%, a total of 26 pts was required to have 90% power at a two-tailed alpha of 0.05. This is a subset analysis of patients with adenocarcinoma in NJLCG1601 study (Trial Identifier, UMIN000020688). ResultsBetween Apr 2016 and Sep 2017, 30 pts were enrolled. Among 30 patients, 28 patients (93%) were adenocarcinoma. Pts characteristics were as follows: median ages, 70 years (range 46-79 years); proportion of males, 43%; clinical stage, IV 61% and post-op 39%; EGFR mutation types, exon 19 deletion 54%, ex21 L858R 36%, and minor mutations 11%. 1-year PFS rate was 53.6% (95% CI, 33.8-69.8), median PFS was 13.0 months, and ORR was 78.6%. Dose reductions occurred in 86% (24/28). Incidence of all cause grade ≧ 3 was 60% which is smaller than the frequency of Japanese subset in LUX-Lung 3. ILD was occurred in 3 patients and 1 patients died. Treatment-related deaths were observed in 2 pts. ConclusionsLow-dose afatinib maintenance treatment reduced treatment-related adverse events without detracting from the therapeutic efficacy. Legal entity responsible for the studyUMIN000020688. FundingHas not received any funding. DisclosureA. Nakamura: Honoraria (self): MSD; Honoraria (self): Chugai; Honoraria (self): AstraZeneca. S. Inoue: Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self): MSD; Honoraria (self): Otsuka Pharmaceutical; Honoraria (self), research funding: Kyorin Pharmaceutical; Honoraria (self): Ono Pharmaceutical; Honoraria (self): GlaxoSmithKline; Honoraria (self): Daiichi Sankyo Company; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Teijin Pharma; Honoraria (self), research funding: Novartis Pharma; Honoraria (self): Pfizer Inc; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Meiji Seika Pharma. S. Sugawara: Honoraria (self): AstraZeneca; Honoraria (self): Chugai Pharma; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Honoraria (self): Novartis; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Ono Pharmaceutical; Honoraria (self): MSD. All other authors have declared no conflicts of interest.

614P - Microsatellite instability status in metastatic colorectal cancer and effect of immune checkpoint inhibitors on survival in MSI-high metastatic colorectal cancer

e15106Background: Tumor mismatch repair (MMR) predicts benefit of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC). We conducted a large-scale prospective observational tr...

1481O - Clinical development of molecular-targeted therapies for non-small cell lung cancer through nationwide genome screening in Japan (LC-SCRUM-Japan)

1481O - Clinical development of molecular-targeted therapies for non-small cell lung cancer through nationwide genome screening in Japan (LC-SCRUM-Japan)

1242P - Clinical utility of precision immunoprofiling and monitoring of the tumour microenvironment using flow cytometry and CyTOF in patients with advanced NSCLC treated with atezolizumab: Results from a phase II study for biomarker analysis (EPOC1702)

1242P - Clinical utility of precision immunoprofiling and monitoring of the tumour microenvironment using flow cytometry and CyTOF in patients with advanced NSCLC treated with atezolizumab: Results from a phase II study for biomarker analysis (EPOC1702)

1557P - A large scale prospective concordance study of oncogene driver detection between plasma- and tissue-based NGS analysis in advanced non-small cell lung cancer (NSCLC)

1557P - A large scale prospective concordance study of oncogene driver detection between plasma- and tissue-based NGS analysis in advanced non-small cell lung cancer (NSCLC)

1458PD - Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer: 10-year follow-up of West Japan thoracic oncology group WJTOG0105

1458PD - Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer: 10-year follow-up of West Japan thoracic oncology group WJTOG0105

526PD - TRIUMPH: Primary efficacy of a phase II trial of trastuzumab (T) and pertuzumab (P) in patients (pts) with metastatic colorectal cancer (mCRC) with HER2 (ERBB2) amplification (amp) in tumour tissue or circulating tumour DNA (ctDNA): A GOZILA sub-study

526PD - TRIUMPH: Primary efficacy of a phase II trial of trastuzumab (T) and pertuzumab (P) in patients (pts) with metastatic colorectal cancer (mCRC) with HER2 (ERBB2) amplification (amp) in tumour tissue or circulating tumour DNA (ctDNA): A GOZILA sub-study

636P - Prognostic and predictive impact on FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

BackgroundFMS-like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis, and FLT3-associated molecular alterations are an established predictor for the treatment with FLT3 inhibitors in acute myeloid leukemia. However, the oncogenic role of FLT3 amplification (amp) in patients (pts) with metastatic colorectal cancer (mCRC) has not yet been well established. MethodsTumor tissue samples from 2,329 mCRC pts were sequenced using next-generation sequencing (NGS) with Oncomine Comprehensive Assay in the Nationwide Cancer Genome Screening Project in Japan (SCRUM-Japan GI-SCREEN). Clinicopathological features, co-altered genes, prognosis and regorafenib efficacy on FLT3 amp (defined as copy number ≥ 7.0) vs. non-FLT3 amp mCRC were investigated. ResultsBetween Apr 2015 and Jun 2018, a total of 85 pts (3.6%) with mCRC with FLT3 amp were observed. There were no clear differences in baseline characteristics between pts with or without FLT3 amp. The enrichment of TP53 mutation in FLT3 amp mCRC was observed more frequently than non-FLT3 amp (74.1% vs. 64.7%, P=0.08), but RAS mutation frequency was similar in both (48.2% vs. 42.8%, P=0.31). In contrast, activating alterations in BRAF (1.1% vs. 7.1%, P=0.053) and PIK3CA (1.1% vs 7.0%, P=0.03) mutations were both less frequent in FLT3 amp vs. non-FLT3 amp mCRC. Median OS from 1st-line chemotherapy in FLT3 amp mCRC was significantly shorter than those in non-FLT3 amp (30.2 vs. 43.4 months, P=0.002). Furthermore, in 20 pts receiving regorafenib, a multikinase inhibitor with a mild inhibitory activity of FLT3, the disease control rate (DCR) was higher in FLT3 amp mCRC pts (n=7) compared with non-FLT3 amp (57.1% vs. 23.0 %, P=0.13). ConclusionsFLT3 amp was associated with a significantly worse survival and a higher DCR from regorafenib, suggesting it has a distinct oncogenic role in mCRC. Further investigation of the oncogenic role of FLT3 amp in mCRC is warranted in clinical trials. Clinical trial identificationUMIN000016344. Legal entity responsible for the studySCRUM-Japan. Funding17 SCRUM-Japan Collaborating Pharmaceutical Companies, AMED, NCC. DisclosureH. Taniguchi: Research grant / Funding (self): Takeda; Advisory / Consultancy: Chugai; Advisory / Consultancy: Taiho. T. Kato: Honoraria (self): Chugai Pharmaceutical; Advisory / Consultancy: Takeda; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Bayer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Yakult Honsya. S. Yuki: Speaker Bureau / Expert testimony: Chugai Pharma; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Bayer Yakuhin; Speaker Bureau / Expert testimony: Ono Pharmaceutical; Speaker Bureau / Expert testimony: Pharma International; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Takeda Pharmaceutical; Speaker Bureau / Expert testimony: Eli Lilly Japan; Speaker Bureau / Expert testimony: Taiho Pharmaceutical; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Yakult Honsha; Speaker Bureau / Expert testimony: Merck Biopharma. T. Masuishi: Honoraria (self): Eli Lilly; Honoraria (self): Chugai Pharma; Honoraria (self): Merck Serono; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Yakult Honsya. K. Kato: Research grant / Funding (self): Shionogi; Research grant / Funding (self): Ono Pharmaceutical; Research grant / Funding (self): Merck Serono. N. Izawa: Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: Sanofi; Advisory / Consultancy: MSD; Advisory / Consultancy: Bayer; Advisory / Consultancy: Bristol-Myers; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck Serono. T. Moriwaki: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Yakult Honsha; Research grant / Funding (institution): Eisai; Speaker Bureau / Expert testimony: Chugai Pharma; Speaker Bureau / Expert testimony: Yakult Honsha; Speaker Bureau / Expert testimony: Merck Serono; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Liliy Japan; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Ono Pharmaceutical. Y. Kagawa: Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: Sanofi; Speaker Bureau / Expert testimony: Taiho. W. Okamoto: Research grant / Funding (institution): MSD. Y. Nakamura: Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Taiho Pharmaceutical. K. Yamazaki: Honoraria (self): Daiichi Sankyo; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Eli Lilly; Honoraria (self): Merck Serono; Honoraria (self), Research grant / Funding (institution): Taiho Pharma; Honoraria (self): Bayer Yakuhin. T. Yoshino: Research grant / Funding (institution): Chugai pharma; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Sumitomo Dainippon pharma; Research grant / Funding (institution): Glaxo SmithKline. All other authors have declared no conflicts of interest.

LBA11 - Nivolumab versus chemotherapy in advanced esophageal squamous cell carcinoma (ESCC): The phase III ATTRACTION-3 study

LBA11 - Nivolumab versus chemotherapy in advanced esophageal squamous cell carcinoma (ESCC): The phase III ATTRACTION-3 study

747P - A phase Ib trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC): Updated results

747P - A phase Ib trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC): Updated results

1764P - A phase III trial evaluating olanzapine 5 mg for the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin: J-FORCE study

BackgroundOlanzapine (OLZ) 10mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. Guidelines suggest that OLZ at a dose of 5mg should be taken into consideration in patients at risk of sedation. OLZ 5mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5mg in addition to standard antiemetic therapy for the prevention of CINV. MethodsPatients receiving cisplatin (≥ 50mg/m2) were randomly assigned to either OLZ 5mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120h). As the secondary endpoints, frequency of sleepiness during daytime and appetite loss were assessed by patient reported outcome. ResultsA total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was significantly increased with OLZ than with placebo (79% vs. 66%, P<0.001). CR in the acute (0–24h) and overall (0–120h) phase was also significantly increased with OLZ (95% vs. 89%, P=0.002, and 78% vs. 64%, P<0.001, respectively). Although the proportion of sleepiness during daytime was higher in the OLZ group than the placebo group on day 1 (75% vs. 68%, P=0.002), there was no difference found on days 2–5 between the two groups. The proportion of patients who reported appetite loss was significantly lower in the OLZ group than the placebo group on days 2–5 (P<0.001). ConclusionsOLZ 5mg can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Sleepiness during daytime due to OLZ 5mg seems to be tolerable and addition of OLZ 5mg to the standard antiemetic therapy may reduce appetite loss. Legal entity responsible for the studyMasakazu Abe. FundingJapan Agency for Medical Research and Development. DisclosureS. Iwasa: Honoraria (self): Taiho pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Ono Pharmaceutical; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Bristol-Myers Squib; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Bayer. N. Yamamoto: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Merck Serono. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, An Immediate Family Member : Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: Celltrion; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): Taiho pharmaceutical; Honoraria (self): Kyowa Hakko Kirin; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Ignyta. All other authors have declared no conflicts of interest.

587P - The impact of late-line treatment on overall survival (OS) from the initiation of first-line chemotherapy (CT) for patients (pts) with metastatic colorectal cancer (mCRC)

BackgroundFor the past 20 years, the improvement in OS has been achieved in mCRC. Active agents including anti-VEGF and anti-EGFR antibodies have contributed to this progress. Late-line treatment with regorafenib (REGO) or trifluridine/tipiracil (FTD/TPI) has also been demonstrated to be effective and these drugs are widely used as standard CT. However, no study has reported to what extent the availability of these two drugs changes the total OS of patients that is measured from the initiation of first-line CT. MethodsWe retrospectively enrolled consecutive mCRC pts at 3 institutions who received first-line CT between Jan 2005 and Sep 2016. We divided the pts into 3 groups according to the availability of drugs at the initiation of first-line CT; pts who started CT between Jan 2005 and Dec 2006 (cohort A: only cytotoxic drugs were available), between Jan 2007 and Dec 2011 (cohort B: anti-VEGF and anti-EGFR antibody were available), or between Jan 2012 and Sep 2016 (cohort C: REGO and FTD/TPI were available). Treatment outcomes were compared among the cohort A, B, and C. ResultsA total of 1,426 pts were analyzed. Pts characteristics of the cohort A (165 pts), B (626 pts), and C (635 pts) were as follows: median age, 62/64/65 years; ECOG PS≥2, 8.5%/8.8%/8.2%; right-sided primary, 26.1%/29.4%/29.9%; tumor grade Grade 3, 10.1%/13.1%/11.9%; KRAS mutation, 28.6%/38.4%/41.1%; and number of metastatic sites ≥2, 63.6%/61.3%/58.1%. In the cohort A, B, and C, 1.2%, 10.7%, and 31.2% of the pts received at least one of late-line treatment with REGO or FTD/TPI. Median OS of the cohort A, B, and C was 18.6 month (M), 25.3 M, and 27.2 M. Hazard ratio (HR) of death was 0.82 (95% confidential interval [CI], 0.68-0.98; p=0.0309) for the cohort B vs A, and 0.71 (95% CI, 0.59-0.86; p=0.0004) for the cohort C vs A, and 0.87 (95% CI 0.77-0.99; p=0.0356) for the cohort C vs B. ConclusionsThis real-world data analysis indicates that late-line treatment with REGO or FTD/TPI could contribute to the prolongation of OS from the initiation of first-line CT for mCRC pts. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureT. Masuishi: Honoraria (self): Taiho Pharmaceutical, Merck Serono, Chugai Pharma, Yakult Honsha, Takeda, Eli Lilly, Bayer Yakuhin, Sanofi; Research grant / Funding (self): Yakult Honsha. Y. Kawamoto: Honoraria (self): Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Chugai Pharmaceutical, Merck Biopharma, Eli Lilly. S. Yuki: Honoraria (self): Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., Eli Lilly Japan K.K., Bayer Yakuhin Co., Ltd., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Pharma International Inc., Yakult H. Y. Komatsu: Honoraria (self): Taiho, Chugai, Yakult, Daiichi Sankyo, Bayer, Merck, Takeda; Research grant / Funding (institution): Taiho, Chugai, Yakult, Daiichi Sankyo, Bayer, Merck, Takeda. K. Muro: Honoraria (self): Takeda, Chugai Pharma, Yakult Honsha, Merck Serono, Taiho Pharmaceutical, Lilly, Ono Pharmaceutical, Bayer; Research grant / Funding (self): Ono Pharmaceutical, MSD, Daiichi Sankyo, Shionogi, Kyowa Hakko Kirin, Gilead Sciences, Merck Serono, Pfizer, Sanofi. T. Yamanaka: Honoraria (self): Chugai, Takeda, Taiho, Boehringer-Ingelheim, Bayer, Pfizer; Advisory / Consultancy: Gilead Sciences, Daiichi-Sankyo, Sysmex, Huya Biosciences; Honoraria (institution): Chugai, Takeda, Taiho, Boehringer-Ingelheim, Bayer, Daiichi-Sankyo, Ono, Merck Serono, Astellas, Eli Lilly. K. Yamazaki: Honoraria (self): Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Bristol-Myers Squibb Japan, Taiho Pharmceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD; Research grant / Funding (institution): Taiho Pharmaceutical. All other authors have declared no conflicts of interest.

801P - Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): An analysis of the TAGS study

801P - Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): An analysis of the TAGS study

LBA4_PR - Nivolumab (NIVO) + low-dose ipilimumab (IPI) vs platinum-doublet chemotherapy (chemo) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): CheckMate 227 part 1 final analysis

LBA4_PR - Nivolumab (NIVO) + low-dose ipilimumab (IPI) vs platinum-doublet chemotherapy (chemo) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): CheckMate 227 part 1 final analysis

685TiP - A phase II basket study of MCLA-128, a bispecific antibody targeting the HER3 pathway, in NRG1 fusion-positive advanced solid tumours

685TiP - A phase II basket study of MCLA-128, a bispecific antibody targeting the HER3 pathway, in NRG1 fusion-positive advanced solid tumours

456P - First-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumours

456P - First-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumours

LBA32 - Encorafenib plus cetuximab with or without binimetinib for BRAF V600E–mutant metastatic colorectal cancer: Expanded results from a randomized, 3-arm, phase III study vs the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC)

LBA32 - Encorafenib plus cetuximab with or without binimetinib for BRAF V600E–mutant metastatic colorectal cancer: Expanded results from a randomized, 3-arm, phase III study vs the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC)

1504P - Phase II study to evaluate the peripheral blood mononuclear cell biomarker for nivolumab efficacy on previously treated non-small cell lung cancer subjects (NEJ029B: IMMUNITY-ONE)

BackgroundAlthough anti-PD-1 antibodies are the most promising agents in advanced non-small cell lung cancer (NSCLC), no definitive biomarkers of efficacy exist. We developed a novel assay for peripheral blood mononuclear cell (PBMC) biomarker using the prediction formula consisting of CD62L-downregulated (CD62Llow) CD4+T cells and CD25+Foxp3+CD4+T cells. This study aimed to validate it. MethodsThis prospective multicenter phase II study included patients with treated advanced or metastatic NSCLC. After registration and PBMC biomarker analysis, they were classified into responder (RT) or non-responder (NRT) type. Nivolumab was administered every two weeks. The primary endpoint was disease control rate (DCR) at nine weeks after nivolumab treatment in RT patients. Desired and threshold DCR were set at 80% and 60%, respectively. Secondary endpoints were objective response rate (ORR), time to treatment failure, progression-free survival (PFS), overall survival, safety and tolerability, comparison with NRT patients, and PBMC biomarker quality improvement. ResultsOf the 96 enrolled patients, 95 were eligible for PBMC analysis: 3 were unanalyzable, and 92 were analyzed; however, 40 had a minimal number of live cells. We excluded 19 patients who did not receive nivolumab in NRT and 1 with indeterminable treatment effect at nine weeks, and 72 patients comprised the per protocol set (PPS), of which 43 were RT and 29 NRT. The DCR and ORR in RT patients were 65.1% (95% confidence interval [CI], 50.9-79.4%) and 14.0% (95% CI, 3.6-24.3%), respectively. The PFS in RT patients was 113 days (95% CI, 65-158). As a subset analysis, we examined 45 patients (25 RT and 20 NRT) excluding those with ≥50% dead cell ratio in lymphocyte culture. The DCR was 80.0% (95%CI, 64.3-95.7) in RT and 50.0% (95% CI, 28.1-71.9) in NRT (chi-square test, p=0.034). ConclusionsIn alive PBMC analysis, DCR was better in the RT than in the NRT patients. This PBMC biomarker using the ratio of CD62LlowCD4+T cells to CD25+Foxp3+CD4+T cells might be promising for predicting nivolumab efficacy. Clinical trial identificationUMIN ID: UMIN000028468. Legal entity responsible for the studyNorth East Japan Study Group (NEJSG). FundingOno Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K. DisclosureO. Yamaguchi: Research grant / Funding (institution): Nihon Medi-Physics Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Ono Pharmaceutical; Speaker Bureau / Expert testimony: Bristol-Myers Squibb. T. Kozuki: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Nippon Beohringer Ingelheim Co.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co.; Honoraria (self): Kyowa-Hakko Kirin; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Merck Biopharm; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical Co.; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical Co. N. Furuya: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Lilly; Honoraria (self): Chugai Pharma ; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Ono Pharmaceutical. T. Yamada: Research grant / Funding (self): Ono Pharmaceutical Co., Ltd.; Research grant / Funding (self): Boehringer Ingelheim Japan Inc.; Research grant / Funding (self): Takeda Pharmaceutical Co. Ltd.; Research grant / Funding (self): Chugai Pharmaceutical Co., Ltd. R. Ko: Honoraria (self): Ono Pharmaceutical Co., Ltd. T. Harada: Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Hisamitsu Pharmaceutical Co., Inc; Honoraria (institution): GlaxoSmithKleine K.K. M. Seike: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb. K. Yoshimura: Honoraria (self): Chugai Pharma. K. Kobayashi: Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Taiho Pharmaceutical Company; Speaker Bureau / Expert testimony: Ono Pharmaceutical Company. H. Kagamu: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan. All other authors have declared no conflicts of interest.