194P Nab-paclitaxel plus capecitabine as first-line treatment for patients with recurrence or metastatic biliary tract cancer

TPS351 Background: Biliary tract cancer (BTC) carries a poor prognosis and no first-line treatments are approved. The accepted global standard of care is gemcitabine + cisplatin (GemCis). NUC-1031 is a phosphoramidate transformation of gemcitabine designed to overcome key cancer resistance mechanisms that are associated with gemcitabine. Promising efficacy has been observed with single-agent NUC-1031 in a phase I study in advanced solid tumors and in the phase Ib ABC-08 study of NUC-1031 + cisplatin for first-line treatment of advanced BTC. Of 14 patients enrolled in 2 cohorts (NUC-1031 625 mg/m2 or 725 mg/m2 + cisplatin 25 mg/m2 on Days 1 and 8 of 21-day cycle), 1 had a CR and 6 had PRs, resulting in an unconfirmed ORR of 50%. This represents an approximate doubling of ORR over SoC. The combination was well-tolerated with no unexpected AEs or DLTs. The RP2D of NUC-1031 with cisplatin was 725 mg/m2. The tolerability profile, together with encouraging efficacy, suggested NUC-1031 + cisplatin may represent a more effective therapy than GemCis for BTC and led to initiation of a global registrational study. Methods: NuTide:121 is a Phase III, open-label, randomized study of NUC-1031 + cisplatin vs GemCis for first-line treatment of advanced BTC. Patients ≥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, are eligible. A total of 828 patients are being randomized (1:1) to either 725 mg/m2 NUC-1031 or 1000 mg/m2 gemcitabine, both with 25 mg/m2 cisplatin, administered on days 1 and 8 of 21-day cycles. Primary objectives are OS and ORR. Secondary objectives include PFS, safety, PK and patient-reported quality of life. In addition to the final analysis, three interim analyses, including two designed to support accelerated approval, are planned. The study has passed an initial safety analysis, with no protocol changes required. NuTide:121 is being conducted at approximately 130 sites across North America, Europe and Asia Pacific countries. Clinical trial information: NCT04163900.

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SHR-1210 combined with GEMOX as first-line treatment in patients with advanced biliary tract cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.535 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 535-535 ◽

Cited By ~ 1

Author(s):

Xiaofeng Chen ◽

Xiaofeng Wu ◽

Hao Wu ◽

Qianwen Shao ◽

Feipeng Zhu ◽

...

Keyword(s):

Biliary Tract ◽

Primary Endpoint ◽

Stable Disease ◽

Biliary Tract Cancer ◽

Combined Chemotherapy ◽

Line Treatment ◽

First Line ◽

Tract Cancer ◽

Grade 3 ◽

First Line Treatment

535 Background: This study aimed to evaluate the efficacy and safety of SHR-1210 (a humanized anti-programmed cell death receptor 1 antibody) plus gemcitabine and oxaliplatin (GEMOX) as first line treatment in patients (pts) with biliary tract cancer (BTC). Methods: This was a single-arm, single-center, exploratory trial, which included advanced BTC pts. Pts received SHR-1210 (3mg/kg, total dose ≤200mg, ivd, D1/2W) combined with gemcitabine (800 mg/m2, ivd, D1/2W) and oxaliplatin (85mg/m2, ivd, D2/2W). Combined chemotherapy lasted for no more than 12 cycles. Once chemotherapy intolerance occurred or at end of 12-cycle combined chemotherapy, pts with stable disease or objective response would continue to take SHR-1210 as single agent until disease progression or intolerable toxicity. The primary endpoint was the 6-month progression free survival (PFS) rate. Results: From February 2018 to April 2019, 37 eligible pts were enrolled. The median age was 64 (range 41-74) years, male/female was 70.3/29.7%, and bile duct cancer/gallbladder cancer was 59.5/40.5%. All 37 pts were included in the safety analysis. The overall AE incidence rate was 97.3%. The incidence of grade ≥3 AEs was 73.0%, which mainly included increased GGT (gammaglutamyltransferase, 18.9%), hypokalemia (18.9%), and fatigue (16.2%). Particularly, the incidence of fever is 73.0%, in which 2 pts experienced grade 3/4 fever. Among 36 evaluable pts, 19 pts got partial response (PR, 52.8%), 14 pts stable disease (SD, 38.9%), and 3 pts progressive disease (PD, 8.3%) at best. The primary endpoint 6-month PFS rate was 50.0% (95% CI 32.4-65.4), which indicated that the primary endpoint of the study was reached, and mPFS was 6.2 months (95% CI 4.2-7.1). The 12-month overall survival (OS) rate was 50.5% (95% CI 30.6-67.4), and mOS was 12.1 months (95% CI 8.0-NA). Conclusions: This study has reached the pre-defined primary endpoint with a high response rate. Predictive biomarker analysis was reported in another abstract. Further study is needed to validate the efficacy of this combination. Clinical trial information: NCT03486678.

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Three-weekly oxaliplatin combined with gemcitabine and capecitabine in the first-line treatment of patients with advanced biliary tract cancer

Anti-Cancer Drugs ◽

10.1097/cad.0000000000000233 ◽

2015 ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Roberto Petrioli ◽

Giandomenico Roviello ◽

Anna I. Fiaschi ◽

Letizia Laera ◽

Franco Roviello ◽

...

Keyword(s):

Biliary Tract ◽

Biliary Tract Cancer ◽

Line Treatment ◽

First Line ◽

Tract Cancer ◽

First Line Treatment

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Cisplatin and gemcitabine plus ramucirumab or merestinib or placebo in first-line treatment for advanced or metastatic biliary tract cancer: A double-blind, randomized phase 2 trial

Annals of Oncology ◽

10.1093/annonc/mdw371.104 ◽

2016 ◽

Vol 27 ◽

pp. vi240 ◽

Cited By ~ 3

Author(s):

J.W. Valle ◽

N. Bousmans ◽

W. Zhang ◽

R.A. Walgren ◽

A. Vogel

Keyword(s):

Biliary Tract ◽

Biliary Tract Cancer ◽

Line Treatment ◽

Phase 2 ◽

First Line ◽

Double Blind ◽

Tract Cancer ◽

Phase 2 Trial ◽

Randomized Phase 2 ◽

First Line Treatment

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3529 POSTER A phase II trial of oxaliplatin with high-dose of 5-fluorouracil and leucovorin in the first-line treatment of inoperable, locally advanced or metastatic biliary tract cancer

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(07)71032-7 ◽

2007 ◽

Vol 5 (4) ◽

pp. 268

Author(s):

J.S. Chen ◽

Y. Chao ◽

T.S. Yang ◽

L.T. Chen ◽

K.D. Lee ◽

...

Keyword(s):

Biliary Tract ◽

Phase Ii ◽

Biliary Tract Cancer ◽

Phase Ii Trial ◽

Locally Advanced ◽

High Dose ◽

Line Treatment ◽

First Line ◽

Tract Cancer ◽

First Line Treatment

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Tumor Mutational Burden as a Biomarker for Advanced Biliary Tract Cancer

Technology in Cancer Research & Treatment ◽

10.1177/15330338211062324 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110623

Author(s):

Hongsik Kim ◽

Hana Kim ◽

Ryul Kim ◽

Hyunji Jo ◽

Hye Ryeon Kim ◽

...

Keyword(s):

Biliary Tract ◽

Biliary Tract Cancer ◽

Objective Response ◽

Progression Free Survival ◽

Line Treatment ◽

First Line ◽

Tract Cancer ◽

Mutational Burden ◽

Tumor Mutational Burden ◽

First Line Treatment

Background: High tumor mutational burden (TMB-H) has been reported as a predictive marker to immunotherapy or prognostic marker in various tumor types. However, there has been little study of the role of TMB-H in advanced biliary tract cancer (BTC). Methods: We analyzed 119 advanced BTC patients who received Gemcitabine/Cisplatin (GP) as a first-line treatment between November 2019 and April 2021. Next-generation sequencing (NGS), including TMB analysis, as a routine clinical practice was performed in 119 patients. The TruSightTM Oncology 500 assay from Illumina was used as a cancer panel. Results: Among 119 patients, 18 (18.5%) had a tumor with high TMB (≥ 10 Muts/Mb). There were no significant differences between the status of TMB and clinical outcomes with GP, including objective response rate (ORR) ( P = .126), disease control rate (DCR) ( p = .454), and median progression-free survival (PFS) ( p = .599). The median overall survival (OS) was not different between patients with TMB-H and no TMB-H ( p = .430). In subgroup analysis of 32 patients receiving immune checkpoint inhibitor (ICIs), there were significant differences in ORR ( p = .034) and median PFS ( p = .025) with ICIs between patients with and without TMB-H. Conclusions: This study revealed that TMB-H in advanced BTCs did not have a prognostic or role in the standard first-line treatment. However, TMB-H might be a predictive biomarker for response to ICIs in advanced BTC.

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