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Found 329 Presentations For Request "biliary tract cancers"
70P - Genomic landscape and efficacy of precision medicine in biliary tract cancers
- Antoine Hollebecque (Villejuif, France)
Abstract
Background
Biliary tract cancers (BTC) are rare and heterogeneous cancers with poor prognosis. Several genomic alterations and genomic targets have been described.
Methods
We performed a retrospective analysis on BTC patients who had a molecular portrait between 2011 and 2019 at Gustave Roussy. The primary objective was to evaluate the prognostic factor of molecular aberrations.
Results
Two hundred and twelve patients (pts) were enrolled. The main characteristics were as follow: median age 61 y/o, female 51%, intrahepatic cholangiocarcinoma 57%, median of 2 previous lines. Of 212 BTC patients, 170 patients had a genomic profile based on archival tissue or a new tumor biopsy (IGR panel n = 117; Foundation One panel n = 95). 460 genomic alterations have been identified among 122 different genes. The most common altered genes were TP53 (9.4%), CDKN2A (7.4%), CDKN2B (5.7%), KRAS (5.4%), IDH1 (4.4%), FGFR2 (4.1%) and PIK3CA (3.7%). TP53 (p=0.008) and HER (p=0.04) were bad prognostic factors whereas FGFR2 fusion was associated with a better prognosis (p=0.03). No significant difference was observed for CDKN2A, CDKN2B, KRAS, IDH, PIK3CA, MYC alteration. Sixty-eight patients had genomic alteration considered as actionable and 58 received the matched targeted therapy. In the treated population, the objective response rate was 36.2% and the disease control rate 85.1%. Progression-free survival (PFS) was 6.2 months compared to 2.8 months (p = 0.02) for patients who did not received targeted treatment.
Conclusions
Biliary tract cancers frequently harbor genomic alterations some of which can lead to specific treatments. that have a prognostic impact. Prognostic role of each molecular abnormality should be studied in order to best assess the potential benefit of treatments.
Legal entity responsible for the study
Antoine Hollebecque.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
51P - Role of biliary extracellular vesicles in diagnosing various pancreatobiliary malignancies
- Mohan V. Turpati (Hyderabad, India)
Abstract
Background
Despite multiple investigations, upto 20% of biliary strictures remain indeterminate. Several recent studies have implicated Extracellular Vesicles (EVs) as potential biomarkers in various cancers. The aim of this study is to evaluate the accuracy of bile EV sizes and concentrations in differentiating malignant from benign biliary stenoses (BS).
Methods
35 patients (20 malignant,15 benign) undergoing ERCP for biliary obstruction were prospectively enrolled at Asian Institute of Gastroenterology, India. Bile was collected upstream from the biliary obstruction before any contrast medium injection. Malignant group included pancreatobiliary cancers and diagnosis was confirmed by histopathological examination (HPE). Benign group included biliary obstruction due to CBD stones and benign biliary strictures. The benign biliary strictures needed a minimum follow up period of 1 year to rule out occult malignancy not apparent on initial evaluation. EV sizes and concentrations were determined by nanoparticle tracking analyses. Area under ROC curve (ROC-AUC) was used to determine a test’s discriminative capability.
Results
Bile EV sizes and concentrations were higher in malignant as compared to benign BS (p<0.05). A cut-off of 9.95×1014 nanoparticles/L in bile distinguished patients with malignant from benign etiologies with 100% accuracy in pancreatic cancer, cholangiocarcinoma and ampullary malignancies (ROC-AUC was 100%). Using the cut-off, it was possible to identify occult malignancies not apparent on either initial imaging or HPE, which were confirmed only during follow-up evaluation. However in patients with gall bladder (GB) cancers causing biliary stricture, bile EV concentrations performed poorly in differentiating malignant from benign BS (ROC-AUC was 50%). Bile from CBD might not have been representative of GB tumor microenvironment and yield can probably be improved by cystic duct cannulation.
Conclusions
Concentration of EVs in bile samples discriminates between patients of malignant from benign biliary stenoses with 100% accuracy in pancreatic, bile duct and ampullary malignancies and might have a role in detecting occult malignancies not apparent on initial clinical, radiological or histopathological examination.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
68P - Analysis of DNA damage repair (DDR) pathway genes in biliary tract cancer and correlation with immunogenic biomarker
- Zhiyu Xiao (Guangzhou, China)
Abstract
Background
Biliary tract cancers (BTC), which include intra-hepatic cholangiocarcinoma (ICC) and extra-hepatic cholangiocarcinoma (ECC), and gallbladder cancers (GC), is an aggressive disease with poor prognosis. The role of DDR pathway genes alterations as a predictive biomarker for the response to platinum-based chemotherapy and Immunotherapy has been reported in many cancers. But the DDR gene characteristics in different subtype BTCs, and its correlation with immunogenic marker such as tumor mutation burden (TMB), microsatellite instability (MSI) and PD-L1 expression was unknown.
Methods
Tumor tissue samples from biliary tract cancers (BTC) were analyzed using next generation sequencing (panel on 381/733-gene). TMB was defined as total number of somatic non-synonymous mutations in coding region. MSI was evaluated by NGS of 500 known MSI loci. PD-L1 expression was evaluated using immunohistochemistry (SP142). Prognostic data of 102 Chinese ICC patients were obtained from cbioportal (Shanghai, Nat Genet 2014). Germ-line or somatic mutations of 180 DDR pathway genes (including Mismatch Repair and Homologous Recombination) were classified as DDR gene mutations.
Results
The DDR mutation frequency in BTC was 19% (191/1193), among 15.33% (125/815) of ICC, 16.67% (4/24) of ECC, and 17.51% (62/354) of GC. ATM mutation was the highest frequency gene in both three type tumors (4.91% of ICC, 5.60% of GC and 8.57% of ECC). In ICC, the highest frequency DDR germ-line mutation gene was BRCA2 (20.00%), followed by PALB2 (12.31%) and BRCA1 (9.23%). In DDR mutation ICC group, the most frequently mutated genes were TP53 (8.93%), KRAS (5.21%) and ARID1A (3.87%), which were both significantly lower than wild-type. DDR mutation was associated with higher TMB (P < 0.01), further in MSS tumors (P < 0.001). No correlation was found with PD-L1 expression. The overall survival (OS) of DDR mutation group (n=32) were shorter than wild-type group (n=70) (OS, median, 10.00 vs 21.00 months; HR 1.5; P = 0.079).
Conclusions
The DDR pathway genes alteration characteristics was presented in different BTC subtypes, and was associated with a higher TMB level. These data provide rationale for future investigation of clinical therapy in DDR mutation BTC.
Legal entity responsible for the study
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University.
Funding
Has not received any funding.
Disclosure
T. Chen, W. Xie, M. Huang: Full/Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.
53P - Toripalimab with chemotherapy as first-line treatment for advanced biliary tract tumors: A preliminary analysis of safety and efficacy of an open-label phase II clinical study
- Tianshu Liu (Shanghai, China)
Abstract
Background
For advanced biliary tract cancers (aBTC), recommended first-line chemotherapy as gemcitabine combined with cisplatin showed limited clinical benefit. Therefore, the phase II study aims to evaluate safety and efficacy of chemotherapy plus toripalimab, an anti-PD-1 antibody, in patients (pts) with aBTC.
Methods
Treatment-naive pts with aBTC received toripalimab (240mg, iv, Q3W), combined with GS (gemcitabine 1000 mg/m2 iv, d1, d8 + S-1 40-60mg bid*14d, Q21d) until the disease progresses or unacceptable toxicity. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were objective response rate (ORR) , safety and biomarker analysis.
Results
At data cutoff (Mar 24, 2020), 39 aBTC pts (female: 51.3%, median age: 64 years, median follow-up time: 10 (2-15) months) were enrolled at Shanghai Zhongshan Hospital. The primary sites of tumor were intrahepatic cholangiocarcinoma (ICC) (41%) extrahepatic cholangiocarcinoma (ECC) (12.8%), and gallbladder (GBC) (46.2%). 34 evaluable pts had a response rate of 20.6% and a 85.3% disease control rate (7 pts PR and 22 pts SD). Median PFS was 6.7 months and OS was immature. The most frequent treatment related AEs (TRAE) were leukopenia (82.1%), anemia (84.6%) and rash (56.4%). Grade III/IV non-hematological TRAEs were seen in 8 pts (20.5%), including rash (n = 3) and infection (n = 5). Grade 3/4 hematological TRAEs were seen in 69.2% pts (leukopenia (51.3%) and thrombocytopenia (17.9%)). 3 pts discontinued the study drug due to TRAE. SAE were seen in 6 pts (5 cases of infection, 1 case of mucositis) and 1 pts died of biliary obstruction complicated with infection. 29 pts were included in biomarker analysis. The most frequently mutated genes were TP53 (59%), CDKN2A (24%) and SMAD4 (21%). Pts with TP53 or ATM alterations had a shorter PFS than wild-type pts (6 months vs. 10.5 months, p=0.036, and 2.8 months vs. 8.2 months, p=0.00037, respectively).
Conclusions
Toripalimab with chemotherapy showed well tolerability and promising efficacy in naïve aBTC. Correlative studies identified potential predictive biomarkers. These results have guided ongoing combinations with Toripalimab in BTC.
Clinical trial identification
NCT03796429.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
52P - Modified FOLFIRINOX versus CISGEM as first-line chemotherapy for advanced biliary tract cancer: Results of AMEBICA PRODIGE 38 randomized phase II trial
- Jean Marc Phelip (Saint-Étienne, cédex 2, France)
Abstract
Background
Combination chemotherapy (CT) with cisplatin and gemcitabine (CISGEM) is the first-line standard of care for patients with advanced biliary tract cancers (BTC). FOLFIRINOX demonstrated an overall survival (OS) improvement in metastatic pancreatic adenocarcinoma compared to gemcitabine monotherapy. We aimed to compare FOLFIRINOX to CISGEM in advanced BTC.
Methods
This open-label, randomized phase II-III study was carried out in 43 French centers. Patients with locally advanced (unresectable) or metastatic BTC, ECOG PS 0-1, were randomly assigned (1:1 ratio) to receive either modified FOLFIRINOX (mFOLFIRINOX, without 5FU bolus at day 1) or CISGEM for 6 months. The primary endpoint in phase II was the progression-free survival rate at 6 months (PFS6) according to RECIST v1.1. 94 patients per arm were needed to test the H1 hypothesis that PFS6 was ≥ 60% (one-sided alpha=5%, power=85%, 73% is expected).
Results
190 patients were randomized (mFOLFIRINOX, 94; CISGEM, 96). Among them, 185 were evaluable (modified intention to treat population, mITT) for the primary endpoint (n=92 and 93, respectively). After a median follow-up of 21 months, the primary endpoint was not reached in the mFOLFIRINOX arm, with a PFS6 of 44.6% [90%CI: 35.7-53.7]. Median PFS (mITT) was 6.2 months [95%CI: 5.5-7.8] in the mFOLFIRINOX arm versus 7.4 months [95%CI: 5.6-8.7] in the CISGEM arm. Median OS was 11.7 months [95%CI: 9.5-14.2] versus 14.3 months [95%CI: 11.3-16.5] respectively. The disease control rates were 66.2% and 69.9% respectively (mainly stable disease). Rates of grade 3-4 adverse events were similar in the mFOLFIRINOX (72.8%) and CISGEM (72.0%) arms, mainly digestive (28.3% vs. 12.9%) and hematologic (32.6% vs. 57.0%).
Conclusions
First-line chemotherapy with mFOLFIRINOX did not meet the primary endpoint. CISGEM remains the first-line standard of care for advanced BTC.
Clinical trial identification
NCT02591030.
Legal entity responsible for the study
Saint Etienne Hospital.
Funding
French National Clinical Research Program in 2014.
Disclosure
J. Edeline: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Research grant/Funding (self): BMS; Research grant/Funding (self): Beigene; Advisory/Consultancy: Eisai; Advisory/Consultancy: Bayer; Advisory/Consultancy: Ipsen; Advisory/Consultancy: BTG. E. Terrebonne: Honoraria (self), Travel/Accommodation/Expenses: Ipsen. P. Michel: Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen. V. Bourgeois: Advisory/Consultancy: Esai; Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Bayer. F. Khemissa Akouz: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Bayer. E. Soularue: Speaker Bureau/Expert testimony: BMS; Travel/Accommodation/Expenses: Servier. F. Ghiringhelli: Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self): Merck Sereno; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Sanofi; Honoraria (self): Boehringer; Research grant/Funding (self), Travel/Accommodation/Expenses: Servier; Honoraria (self), Research grant/Funding (self): Sobi. R. Coriat: Advisory/Consultancy: Amgen; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ipsen AAA; Advisory/Consultancy: Bayer; Advisory/Consultancy: Servier. C. Neuzillet: Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Nutricia; Honoraria (self), Advisory/Consultancy: Baxter; Honoraria (self), Advisory/Consultancy: Fresenius Kabi; Travel/Accommodation/Expenses: OSE Immunotherapeutics; Research grant/Funding (institution): Roche. S. Manfredi: Research grant/Funding (self), Travel/Accommodation/Expenses: Lilly France SAS; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Ipsen Pharma; Travel/Accommodation/Expenses: Roche SAS; Travel/Accommodation/Expenses: Amgen SAS; Travel/Accommodation/Expenses: Janssen-Cilag; Travel/Accommodation/Expenses: MSD France; Travel/Accommodation/Expenses: Novartis Pharma SAS; Travel/Accommodation/Expenses: Sirtex Medical Europe GmbH. D. Malka: Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Serono; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy: HalioDx; Advisory/Consultancy: Agios; Advisory/Consultancy: Pierre Fabre Oncologie; Advisory/Consultancy: Incyte; Advisory/Consultancy: Novartis. All other authors have declared no conflicts of interest.
55P - Adjuvant gemcitabine-based chemotherapy for biliary tract cancer: Pooled analysis of the BCAT and PRODIGE-12 studies
- Julien Edeline (Rennes, CEDEX, France)
Abstract
Background
While gemcitabine-based chemotherapy (GBCT) is the first-line standard of care for patients with advanced biliary tract cancers (BTC), adjuvant phase III studies (BCAT and PRODIGE 12) failed to show benefit, possibly because of a lower power due to fewer patients (n=225 and n=194) compared to the adjuvant capecitabine BILCAP trial (n=447). We performed a pooled analysis of both GBCT adjuvant studies.
Methods
Individual patient data pooled analysis of all patients included in BCAT and PRODIGE 12. BCAT randomized patients with extrahepatic cholangiocarcinoma (CC) to single-agent gemcitabine for 6 months or observation. PRODIGE 12 randomized patients with all BTC subtypes to gemcitabine-oxaliplatin combination for 6 months or observation. Combined analysis was done using Kaplan-Meier curves and a Cox regression model stratified on the trial. We studied overall survival (OS) and relapse-free survival (RFS).
Results
212 vs 207 patients were randomized in the GBCT vs observation arms. Mean age (66.3 vs 64.7), sex (male, 63.2% vs 63.8%), R1 status (11.3% vs 12.6%), N1 status (36.3% vs 34.8%), primary tumor location (distal CC, 43.9% vs 41.1%; perihilar CC, 28.8% vs 27.1%; intrahepatic CC, 19.3% vs 21.7%; gallbladder carcinoma, 8.0% vs 10.1%) were balanced between arms. There were differences between populations included in the trials (p<0.001 for age, sex, N1 status, primary tumor location and total gemcitabine dose). The median follow-up was 5.5 years. After 258 RFS events, there was no difference in RFS: median 2.9 years (95%CI: 1.8-3.8) for GBCT vs 2.1 years (95%CI: 1.4-3.4) for observation (log-rank p=0.45; hazard ratio (HR)=0.91 [95%CI 0.71-1.16]; p=0.46). Respective RFS rates at 5 years were 40.8% (95%CI: 33.9%-47.5%) vs 36.6% (95%CI: 29.8%-43.4%). After 201 deaths, there was no difference in OS: median 5.1 years (95%CI: 3.4-7.0) for GBCT vs 5.0 years (95%CI: 3.9-NA) for observation (log-rank p=0.83; HR=1.03 [95%CI: 0.78-1.35]; p=0.85). Respective OS rates at 5 years were 50.5% (95%CI: 43.1%-57.4%) vs 49.3% (95%CI: 41.6%-56.5%).
Conclusions
With 419 patients included, this pooled analysis of BCAT and PRODIGE 12 did not show any improvement in RFS or OS. GBCT should not be used as an adjuvant treatment for BTC.
Clinical trial identification
PRODIGE 12: EudraCT 2008-004560-39. BCAT: UMIN 000000820.
Legal entity responsible for the study
Unicancer.
Funding
Programme Hospitalier de Recherche Clinique (PHRC-2009) and Ligue Nationale Contre le Cancer.
Disclosure
J. Edeline: Honoraria (self), Research grant/Funding (self): BMS; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Beigene; Honoraria (self): Bayer; Honoraria (self): Eisai; Honoraria (self): Ipsen; Honoraria (self): BTG; Honoraria (self): Roche. M. Benabdelghani: Honoraria (self): Servier; Honoraria (self): Ipsen; Honoraria (self): Amgen; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Bayer. P. Hammel: Honoraria (self): BMS; Honoraria (self): Servier; Honoraria (self): AstraZeneca. D. Malka: Honoraria (self): Amgen; Honoraria (self): Bayer; Honoraria (self): MSD; Honoraria (self): Merck Serono; Honoraria (self): Servier; Honoraria (self): Agios; Honoraria (self): Incyte; Honoraria (self): Novartis; Honoraria (self): Sanofi; Honoraria (self): Roche; Honoraria (self): HalioDX; Honoraria (self): Pierre Fabre Oncologie. All other authors have declared no conflicts of interest.
73P - Long-term follow-up of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract cancer
- Changhoon Yoo (Seoul, Songpa-gu, Korea, Republic of)
Abstract
Background
Biliary tract cancer (BTC) is a rare, heterogenous, and lethal group of cancers with limited treatment options. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Prior analysis of this phase I study found an objective response rate of 23.3% and a manageable safety profile in patients with pretreated BTC who received bintrafusp alfa 1200 mg. We present long-term follow-up safety and efficacy data for bintrafusp alfa in patients with pretreated BTC.
Methods
In this expansion cohort of an ongoing phase I, open-label trial (NCT02699515), Asian patients with BTC for which first-line (1L) chemotherapy failed received bintrafusp alfa 1200 mg Q2W until confirmed disease progression, unacceptable toxicity, or withdrawal. The primary objective was safety/tolerability; secondary objectives included investigator-assessed best overall response per RECIST 1.1.
Results
As of 24 October 2019, 30 patients with pretreated BTC received bintrafusp alfa for a median duration of 8.9 (range, 2-140.1) weeks; median follow-up was 122 weeks, 8 patients were still alive and 3 remained on treatment. The overall safety profile remained consistent with the prior analysis; with no additional deaths or safety signals, and 2 new grade ≥3 TRAEs (grade 3 rash and grade 3 keratoacanthoma). The median overall survival (OS) was 12.7 months [95% CI, [6.7-15.8]; the 12- and 24-month OS rates were 52.0% and 27.7%, respectively. The median duration of response was 18 (range, 2.8-24+) months, with 3 ongoing responses (18+, 23.5+, and 24+ months) of 7 responders (42.8%); the proportion of ongoing responses at 12 and 18 months was 57.1% and 42.8%, respectively.
Conclusions
After 28 months, bintrafusp alfa continues to demonstrate manageable safety with durable responses and long-term survival in Asian patients with pretreated BTC. Bintrafusp alfa is under further investigation as a 1L (NCT04066491) and 2L (NCT03833661) treatment option for patients with locally advanced/metastatic BTC.
Clinical trial identification
NCT02699515.
Editorial acknowledgement
Medical writing support was provided by Spencer Hughes, PhD, of ClinicalThinking, Inc, Hamilton, NJ, USA, and funded by Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline.
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Funding
Merck KGaA, Darmstadt, Germany and GlaxoSmithKline.
Disclosure
C. Yoo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Servier; Honoraria (self): Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Ono Pharmaceuticals. D-Y. Oh: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Bayer; Advisory/Consultancy: Taiho; Advisory/Consultancy: ASLAN; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Zymeworks; Advisory/Consultancy: Celgene; Research grant/Funding (self): Array; Research grant/Funding (self): Eli Lilly. H.J. Choi: Advisory/Consultancy: Bayer; Advisory/Consultancy: ONO; Advisory/Consultancy: MSD. M. Kudo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self): Bayer; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): Lilly; Honoraria (self), Research grant/Funding (institution): EA Pharma; Advisory/Consultancy: Ono; Advisory/Consultancy: Roche; Research grant/Funding (institution): Gilead Sciences; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Sumitomo Dainippon Pharma; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Otsuka; Research grant/Funding (institution): Abbvie. M. Ueno: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Yakult Honsha; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Merck Biopharma; Honoraria (self), Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Dainippon Sumitomo Pharma; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Astellas. S. Kondo: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Abbie; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): AZD; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Boehringer Ingelheim. L-T. Chen: Honoraria (self): ONO; Honoraria (self): Eli Lilly; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy: PharmaEngine; Honoraria (self), Research grant/Funding (institution): TTY; Honoraria (self), Research grant/Funding (institution): SyncorePharm; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Leadership role: National Institute of Cancer Research, Taiwan; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Polaris; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): BMS; Licensing/Royalties, ENO-1 mAb: HuniLife; Full/Part-time employment: National Health Research Institutes, Taiwan; Officer/Board of Directors: SinoPharm Taiwan, Ltd. M. Osada: Full/Part-time employment: Merck Biopharma. C. Helwig: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck KGaA. I. Dussault: Full/Part-time employment: EMD Serono. M. Ikeda: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self): Taiho; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self): Teijin; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Astrazeneca; Research grant/Funding (institution): Ono; Research grant/Funding (institution): Bristol Myers; Research grant/Funding (institution): MSD; Research grant/Funding (self): J-Pharma; Research grant/Funding (institution): ASLAN; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Astellas.
62P - Prognostic significance of baseline neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) in patients (pts) with biliary tract cancer (BTC)
- Noor-Ul-Ain Tariq (Metropolitan Borough of Wirral, United Kingdom)
Abstract
Background
Biliary tract cancer is a poor prognosis disease. Due to the role of chronic inflammation in the development of BTC, inflammatory markers such as NLR, PLR, and SII might be useful as prognostic markers in this disease group.
Methods
Data from sequential pts with BTC referred to The Christie (Jan 2012 - Aug 2017) were reviewed retrospectively. Median (med) value was used to dichotomise subgroups for baseline NLR, PLR and SII (Platelets x Neutrophils/Lymphocytes) for balanced division of patients. The Kaplan-Meier survival method was used and association of overall survival (OS) with different co-variables was analysed using Cox proportional hazard regression.
Results
Data from 591 pts were included; median age was 69 years, 46% were males, Eastern Co-operative Oncology Group performance status (ECOG PS) 1 was the commonest PS (51.1%). Patients had extrahepatic cholangiocarcinoma (CCA): 32.3%, intrahepatic CCA: 28.7%, gallbladder carcinoma: 20.6%, or ampulla of Vater carcinoma: 15.9%. Stage: 54.2% stage IV, 32.5% stage III, and 13.2% stage I/II; 89% of pts had died at time of analysis. The cut-off for NLR was ≥3.64, PLR was ≥193.3 and SII was ≥1082.1. The median OS for the entire cohort was 13.4 months (mths) (95% Confidence Interval [CI] 12-14.8); the 5-year survival rate was 5.1% (95%CI 3.3-7.9). The multivariable analysis was adjusted for gender, age, stage, ECOG PS, treatment type, and NLR, PLR and SII at baseline as these were significant at univariate analysis. On multivariable analysis, NLR (HR 1.34, 95%CI 1.1-1.7, p=0.01) and SII (HR 1.57, 95%CI 1.2-2.0, p<0.001) were both independent prognostic factors, with better OS in patients with lower NLR (med OS 17.7 mths vs 9.2 mths, [95% CI 16.66-22.3], p<0.001) and lower SII (med OS 17.9 mths vs 8.6 mths [95% CI 16.26-22.16], p<0.001).
Conclusions
Lower baseline NLR and SII were prognostic for better OS in pts with BTC. Prospective studies are needed to explore the clinical prognostic relevance of these markers.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N-U-A. Tariq: Honoraria (self), Travel/Accommodation/Expenses: Boehringer-Ingelheim; Travel/Accommodation/Expenses: Roche; Honoraria (self): AstraZeneca. A. Lamarca: Advisory/Consultancy: EISAI; Advisory/Consultancy: Nutricia; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy: QED; Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony: Merck; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony: Incyte; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AAA; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: SirtEx; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Mylan and Declath. R. Hubner: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: Ipsen; Advisory/Consultancy: BTG; Speaker Bureau/Expert testimony: Prime Oncology; Travel/Accommodation/Expenses: Bayer. M.G. McNamara: Research grant/Funding (self): Servier; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Nucana; Honoraria (self), Speaker Bureau/Expert testimony: Pfizer; Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Celgene; Advisory/Consultancy: Sirtex; Advisory/Consultancy: Baxalta; Advisory/Consultancy: Incyte. J.W. Valle: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy: Agios; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Debiopharm; Advisory/Consultancy: Delcath Systems; Advisory/Consultancy: GenoScience Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Imaging Equipment Ltd; Advisory/Consultancy: Incyte; Advisory/Consultancy: Keocyt; Advisory/Consultancy: Merck; Advisory/Consultancy: Mundipharma EDO; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Nucana; Advisory/Consultancy: PCI Biotech; Advisory/Consultancy: Pieris Pharmaceuticals; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: QED; Advisory/Consultancy: Servier; Advisory/Consultancy: Wren Laboratories; Travel/Accommodation/Expenses: Celgene. All other authors have declared no conflicts of interest.
78TiP - KEYNOTE-966 trial in progress: Pembrolizumab plus gemcitabine and cisplatin for advanced biliary tract cancer
- Juan W. Valle (Manchester, United Kingdom)
Abstract
Background
Biliary tract cancer (BTC), comprising intra- and extra-hepatic cholangiocarcinoma and gallbladder cancer, is a rare and aggressive malignancy. Most patients (pts) present with advanced or unresectable disease, for which the current standard of care is gemcitabine plus cisplatin. Median survival for these pts is only 12 months, highlighting the need for more effective therapies. Pembrolizumab is a PD-1 inhibitor that has demonstrated modest antitumor activity as monotherapy in pts with previously treated BTC and has improved survival when used in combination with platinum-based chemotherapy in other cancer types.
Trial design
KEYNOTE-966 (NCT04003636) is a randomized, double-blind, phase III trial designed to evaluate the efficacy and safety of pembrolizumab plus gemcitabine and cisplatin versus placebo plus gemcitabine and cisplatin in pts with previously untreated advanced BTC. Key eligibility criteria include age ≥18 years, histologically confirmed metastatic or unresectable BTC, measurable disease per RECIST v1.1, ECOG performance status 0/1, and no prior systemic therapy for advanced BTC. Pts with past or ongoing hepatitis C or controlled hepatitis B virus infection are eligible per protocol-defined criteria. Approximately 788 pts will be randomly allocated 1:1 to pembrolizumab 200 mg or placebo IV every 3 weeks in combination with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 IV on days 1 and 8 of every 3-week cycle. Pembrolizumab will be continued for ≤35 cycles or until progression, unacceptable toxicity, or withdrawal. Gemcitabine will be continued until progression, unacceptable toxicity, or withdrawal. Cisplatin will be given for a maximum of 8 cycles. Primary endpoints are progression-free survival and overall survival. Secondary endpoints are objective response rate, duration of response, and safety. Exploratory endpoints include disease control rate and health-related quality of life. Tumor imaging by CT or MRI will be performed every 6 weeks until week 54, and every 12 weeks thereafter. Adverse events will be monitored throughout the study and graded according to NCI CTCAE v.5.0. Recruitment began in September 2019 and is underway in 19 countries.
Clinical trial identification
NCT04003636.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp.
Legal entity responsible for the study
Merck Sharp & Dohme Corp.
Funding
Merck Sharp & Dohme Corp.
Disclosure
J.W. Valle: Advisory/Consultancy, Speaker Bureau/Expert testimony: Imaging Equipment Ltd; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nucana; Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Agios; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Debiopharm; Advisory/Consultancy: Delcath Systems; Advisory/Consultancy: GenoScience Pharma; Advisory/Consultancy: Incyte; Advisory/Consultancy: Keocyt; Advisory/Consultancy: Merck; Advisory/Consultancy: Mundipharma EDO; Advisory/Consultancy: PCI Biotech; Advisory/Consultancy: Pieris Pharmaceuticals; Advisory/Consultancy: QED; Advisory/Consultancy: Wren Laboratories; Advisory/Consultancy: Servier. R.K. Kelley: Advisory/Consultancy, Payments to self (advisory board): Genentech/Roche; Advisory/Consultancy, Payments to self (advisory board): Gilead; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for advisory board/steering committee service: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for advisory board/steering committee service: Agios; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for advisory board/steering committee service: BMS; Advisory/Consultancy, Research grant/Funding (institution), Payment to institution for advisory board/steering committee service: Merck; Travel/Accommodation/Expenses: Ipsen; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Partner Therapeutics; Research grant/Funding (institution): QED; Research grant/Funding (institution): Taiho. J. Furuse: Honoraria (self): Eisai, Bayer Yakuhin, Taiho Pharmaceutical, Ono Pharmaceutical, Novartis, Yakult Honsha, Teijin pharma, Shionogi, EA pharma, Eli Lilly Japan, Takeda, Chugai Pharma, Fujifilm, Mochida Pharmaceutical, Nihon Servier, Sanofi, Fujifilm Toyama Chemical, Nobel p; Research grant/Funding (institution): Eisai, Fujifilm, Ono Pharmaceutical, Yakult Honsha, Taiho Pharmaceutical, Eli Lilly Japan, Astellas Pharma, AstraZeneca, Abbvie, Shire, Merck Serono, Takara Bio, Chugai Pharma, Bayer Yakuhin, Otsuka, Novartis, MSD, Sumitomo Dainippon, J-Pharma. J. Edeline: Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ipsen; Advisory/Consultancy: BTG; Research grant/Funding (self): Beigene; Travel/Accommodation/Expenses: Amgen. R.S. Finn: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Exelixis; Advisory/Consultancy: C Stone Pharma. Z. Ren: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Merck. S-C. Su: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: MSD. U. Malhotra: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: MSD. A.B. Siegel: Full/Part-time employment: Merck & Co., Inc.; Shareholder/Stockholder/Stock options: MSD. A. Vogel: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Sanofi; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self): Decalth Systems; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self): Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Baxalta; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: BTG.
79TiP - A phase II/III, randomized, placebo-controlled study of bintrafusp alfa with gemcitabine plus cisplatin as first-line treatment of biliary tract cancer
- Do-Youn Oh (Seoul, Korea, Republic of)
Abstract
Background
Gemcitabine + cisplatin is the current standard of care for first-line treatment of patients with locally advanced/metastatic biliary tract cancer (BTC), but survival outcomes are poor. Aberrant TGF-β signaling may be associated with BTC pathogenesis; TGF-β activity in tumors may lead to resistance to anti–PD-(L)1 therapies. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. In murine models, the combination of bintrafusp alfa and chemotherapy resulted in improved antitumor activity over either therapy alone. Bintrafusp alfa monotherapy previously demonstrated clinical activity and manageable safety in BTC for which standard chemotherapy failed in an expansion cohort from a phase I study (NCT02699515); the objective response rate (ORR) was 20% per independent review. In this phase II/III study, the efficacy and safety of bintrafusp alfa and gemcitabine + cisplatin vs gemcitabine + cisplatin will be evaluated.
Trial design
This multicenter, phase II/III study (NCT04066491) of patients with histologically/cytologically confirmed BTC, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer, has an open-label safety run-in part and a randomized, double-blind, placebo-controlled part. Patients may not have received treatment for locally advanced/metastatic disease and must have an ECOG performance status of ≤1. Patients who have had interstitial lung disease will be excluded. In the open-label safety run-in part, ≥12patients will receive bintrafusp alfa (2400 mg Q3W) and gemcitabine + cisplatin (D1 and D8 Q3W for 8 cycles) followed by bintrafusp alfa monotherapy (2400 mg Q3W). In the randomized part, ≤500 patients will be randomized 1:1 to receive bintrafusp alfa (2400 mg) or placebo Q3W in addition to gemcitabine + cisplatin (D1 and D8 Q3W for 8 cycles). The primary endpoint of the randomized part is overall survival; key secondary endpoints include progression-free survival, ORR, and safety. Estimated enrollment is 512 patients.
Clinical trial identification
NCT04066491.
Editorial acknowledgement
Medical writing support was provided by Spencer Hughes, PhD, of ClinicalThinking, Inc, Hamilton, New Jersey, USA, and funded by Merck KGaA, Darmstadt, Germany and GlaxoSmithKline.
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Funding
Merck KGaA, Darmstadt, Germany and GlaxoSmithKline.
Disclosure
D-Y. Oh: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Bayer; Advisory/Consultancy: Taiho; Advisory/Consultancy: ASLAN; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Zymeworks; Advisory/Consultancy: Celgene; Research grant/Funding (self): Array; Research grant/Funding (self): Eli Lilly. F. de Braud: Advisory/Consultancy: Tiziana Life Sciences; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Servier; Advisory/Consultancy: Pharm Research Associated; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ignyta; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Octimet Oncology; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Astra Zeneca; Advisory/Consultancy: Gentili; Advisory/Consultancy, Speaker Bureau/Expert testimony: Dephaforum; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: Fondazione Menarini; Speaker Bureau/Expert testimony: Biotechespert Ltd; Speaker Bureau/Expert testimony: Prime Oncology; Research grant/Funding (institution): NMS; Research grant/Funding (institution): Merck KGAA; Research grant/Funding (institution): Kymab; Research grant/Funding (institution): Tesaro. J. Bridgewater: Advisory/Consultancy: Merck-Serono; Advisory/Consultancy: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Research grant/Funding (institution): Incyte; Travel/Accommodation/Expenses: MSD. J. Furuse: Honoraria (self): Eisai; Honoraria (self): Bayer Yakuhin; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (institution): Yakult Honsha; Honoraria (self): Teijin Pharma; Honoraria (self): Shionogi; Honoraria (self): EA Pharma; Honoraria (self), Research grant/Funding (institution): Eli Lilly Japan; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): Mochida Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Nihon Servier; Honoraria (self), Research grant/Funding (institution): Sanofi; Honoraria (self): Fujifilm Toyama Chemical; Honoraria (self): Nobel Pharma; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): Sawai Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self), Research grant/Funding (institution): Sumitomo Dainippon; Honoraria (self): Merck Serono; Honoraria (self): Nippon Kayaku; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): Shire; Honoraria (self), Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): J-Pharma; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): NanoCarrier; Research grant/Funding (institution): Bayer. C-H. Hsu: Honoraria (self), Advisory/Consultancy: Bristol-Meyers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Genentech; Advisory/Consultancy: Merck Serono. M. Ikeda: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self): Taiho; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self): Teijin; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Ono; Research grant/Funding (institution): Bristol Myers; Research grant/Funding (institution): MSD; Research grant/Funding (institution): J-Pharma; Research grant/Funding (institution): ASLAN; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Astellas. M. Javle: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: QED; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Incyte; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Taiho; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Klus; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Arqule; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astra Zeneca; Speaker Bureau/Expert testimony: Agios. M. Moehler: Research grant/Funding (institution): MSD; Advisory/Consultancy: Falk Foundation; Advisory/Consultancy: Lilly; Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: MCI Group. J.O. Park: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Servier; Advisory/Consultancy, Research grant/Funding (self): Celgene; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Merck Serono; Research grant/Funding (self): MedPacto. C. Yoo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Servier; Honoraria (self): Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Ono Pharmaceuticals. C. Helwig: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck KGaA. M. Osada: Full/Part-time employment: Merck Biopharma. M. Borad: Research grant/Funding (institution): Senhwa Pharmaceuticals; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): Agios Pharmaceuticals; Research grant/Funding (institution): Halozyme Pharmaceuticals; Research grant/Funding (institution): Celgene Pharmaceuticals; Research grant/Funding (institution): EMD Merck Serono; Research grant/Funding (institution): Toray; Research grant/Funding (institution): Dicerna; Research grant/Funding (institution): Taiho Pharmaceuticals; Research grant/Funding (institution): Sun Biopharma; Research grant/Funding (institution): Isis Pharmaceuticals; Research grant/Funding (institution): Redhill Pharmaceuticals; Research grant/Funding (institution): Boston Biomed; Research grant/Funding (institution): Basilea; Research grant/Funding (institution): Incyte Pharmaceuticals; Research grant/Funding (institution): Mirna Pharmaceuticals; Research grant/Funding (institution): Medimmune; Research grant/Funding (institution): Bioline; Research grant/Funding (institution): Sillajen; Research grant/Funding (institution): ARIAD Pharmaceuticals; Research grant/Funding (institution): PUMA Pharmaceuticals; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): QED; Research grant/Funding (institution): Pieris; Advisory/Consultancy: ADC Therapeutics; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Inspyr; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Immunovative Therapies; Advisory/Consultancy: OncBioMune; Advisory/Consultancy: Western Oncolytics; Advisory/Consultancy: Lynx Group; Advisory/Consultancy: Genentech; Advisory/Consultancy: Merck; Advisory/Consultancy: Huya; Travel/Accommodation/Expenses: Astra Zeneca. All other authors have declared no conflicts of interest.
80TiP - Global phase III study of NUC-1031 plus cisplatin vs gemcitabine plus cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121)
- Jennifer J. Knox (Toronto, ON, Canada)
Abstract
Background
The prognosis for patients (pts) with biliary tract cancer (BTC) is poor with no approved first-line treatments. Although gemcitabine + cisplatin (GemCis) is accepted as the global standard of care (SoC) for treatment of advanced BTC, the reported unconfirmed ORR and OS from randomised studies are low at 18-26% and 11.2-11.7 months, respectively. NUC-1031, a phosphoramidate transformation of the active metabolite of gemcitabine, is designed to overcome key cancer resistance mechanisms associated with gemcitabine. Promising efficacy has been achieved with single-agent NUC-1031 in a phase I study in advanced solid tumours and in the phase Ib ABC-08 study of NUC-1031 + cisplatin for first-line treatment of pts with advanced BTC. Of 14 pts enrolled, 1 achieved a CR and 6 achieved PR, giving an unconfirmed ORR of 50%, representing an approximate doubling of ORR over SoC. The combination was well-tolerated with no unexpected AEs or dose-limiting toxicities. The tolerability profile together with robust efficacy signals suggested NUC-1031 + cisplatin may represent a more effective therapy than GemCis for pts with advanced BTC and led to initiation of a global registrational study, NuTide:121.
Trial design
A phase III, open-label, randomised study of NUC-1031 + cisplatin versus GemCis for first-line treatment of advanced BTC includes pts ≥18 years with histologically- or cytologically-confirmed BTC (including cholangiocarcinoma, gallbladder, or ampullary cancer), who have had no prior systemic chemotherapy for locally advanced/metastatic disease. 828 pts are being randomised (1:1) to either NUC-1031 (725 mg/m2) + cisplatin (25 mg/m2) or gemcitabine (1000 mg/m2) + cisplatin (25 mg/m2), administered on Days 1 and 8 of a 21-day cycle. Primary objectives are OS and ORR. Secondary objectives include PFS, safety, PK, pt-reported quality of life and correlative studies. Three interim analyses, including two designed to support accelerated approval, are planned, in addition to the final analysis. The study is being conducted at approximately 120 sites across North America, Europe and Asia Pacific countries.
Clinical trial identification
NCT04163900.
Legal entity responsible for the study
NuCana plc.
Funding
NuCana plc.
Disclosure
J.J. Knox: Advisory/Consultancy: Lilly; Speaker Bureau/Expert testimony, Research grant/Funding (self): Merck; Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Honoraria (self): Novartis; Research grant/Funding (self): Ipsen. M.G. McNamara: Advisory/Consultancy, Research grant/Funding (self): Ipsen; Advisory/Consultancy: Shire; Advisory/Consultancy: Sirtex Medical; Speaker Bureau/Expert testimony, Research grant/Funding (self): NuCana; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Novartis; Research grant/Funding (self): Servier. L. Goyal: Advisory/Consultancy, Travel/Accommodation/Expenses: Debiopharm Group; Advisory/Consultancy: Alentis Therapeutics; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: H3 Biomedicine; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Klus Pharma; Advisory/Consultancy: Agios; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Taiho Pharmaceutical. M. Doherty: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Roche Canada; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy: Eisai; Advisory/Consultancy: Boehringer Ingelheim. D. Cosgrove: Full/Part-time employment: Compass Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony, Full/Part-time employment: Biocompatabilites; Leadership role, Travel/Accommodation/Expenses: US Oncology. C. Springfeld: Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy: Eisai; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD. K. Sjoquist: Honoraria (institution): Merck; Honoraria (institution): Amgen; Honoraria (institution): Servier; Honoraria (institution): Bristol-Myers-Squibb; Research grant/Funding (institution): Bayer. J.O. Park: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Celgene; Advisory/Consultancy: Shire; Advisory/Consultancy: Merck Sereno; Advisory/Consultancy: Sanofi; Advisory/Consultancy: SERVIER; Advisory/Consultancy: AstraZeneca. C. Braconi: Travel/Accommodation/Expenses: Menarini Silicon Biosystems; Honoraria (self): Pfizer; Honoraria (self): Lilly; Honoraria (self): Merck Serono; Honoraria (self): Bayer. P. Ross: Honoraria (self), Advisory/Consultancy: Sirtex Medical; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: SERVIER; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Shire; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Sanofi. J.R. Zalcberg: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Advisory/Consultancy: Targovax; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy: Sirtex Medical; Honoraria (self), Advisory/Consultancy: Halozyme; Advisory/Consultancy: Lipotek; Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Deciphera; Shareholder/Stockholder/Stock options: GW Pharmaceuticals; Shareholder/Stockholder/Stock options: Aimmune; Shareholder/Stockholder/Stock options: Vertex; Shareholder/Stockholder/Stock options: Bluebird Bio; Shareholder/Stockholder/Stock options: Alnylam; Shareholder/Stockholder/Stock options: Biomarin; Shareholder/Stockholder/Stock options: Sage Therapeutics; Shareholder/Stockholder/Stock options: Dova Pharmaceuticals; Shareholder/Stockholder/Stock options: TherapeuticsMD; Shareholder/Stockholder/Stock options: Juno Therapeutics; Shareholder/Stockholder/Stock options: Kita Pharma; Shareholder/Stockholder/Stock options: Kiadis Pharma; Shareholder/Stockholder/Stock options: CSL Limited; Shareholder/Stockholder/Stock options: Cochlear; Honoraria (self), Research grant/Funding (institution): Specialised Therapeutics; Honoraria (self): Gilead Sciences; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Baxalta/Shire; Research grant/Funding (institution): Lilly. D. Palmer: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Sirtex Medical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: NuCana; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Eisai Europe Ltd; Research grant/Funding (self): BTG. J.W. Valle: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Delcath Systems; Advisory/Consultancy: Agios; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: PCI Biotech; Advisory/Consultancy: Incyte; Advisory/Consultancy: Keocyte; Advisory/Consultancy: QED Therapeutcs; Advisory/Consultancy: Pieris Pharmaceuticals; Advisory/Consultancy: Genoscience Pharma; Advisory/Consultancy: Mundipharma EDO GmbH; Advisory/Consultancy: Wren Laboratories; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: NuCana; Advisory/Consultancy: SERVIER; Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy, Speaker Bureau/Expert testimony: Imaging Equipment Limited; Travel/Accommodation/Expenses: Celgene. All other authors have declared no conflicts of interest.
69P - PD-L1 expression as a prognostic marker in patients with advanced biliary tract cancer
- Hyera Kim (Daegu, Korea, Republic of)
Abstract
Background
Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered as a novel biomarker for prognosis and response of immune checkpoint inhibitors (CPIs) in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients.
Methods
We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score (CPS) positivity.
Results
In all 186 patients, the median age was 62 years (range 38-82), and the primary tumor location was intrahepatic cholangiocarcinoma (IH-CCC) in 72 patients (38.7%), extrahepatic (EH)-CCC in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). There were 158 (84.9%) patients with recurrent disease and 28 (15.1%) with metastatic disease. Among the 186 patients, 53 (28.5%) had PD-L1 CPS positivity, and 133 were CPS negative. The median overall survival (OS) of patients with PD-L1 CPS positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. The OS and PFS were not statistically different between groups. In sub-group analysis, EH-CCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months,
Conclusions
This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EH-CCC but not for patients with IH-CCC or GB cancer.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.