A phase II trial of trastuzumab plus modified-FOLFOX for gemcitabine/cisplatin refractory HER2-positive biliary tract cancer (BTC): Multi-institutional study of the Korean Cancer Study Group (KCSG-HB19-14).

person Choong-kun Lee Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea info_outline Choong-kun Lee, Jaekyung Cheon, Hong Jae Chon, Min Hwan Kim, Jin Won Kim, Myung Ah Lee, Hyung Soon Park, Myoung Joo Kang, Joung-Soon Jang, Hye Jin Choi

Authors person Choong-kun Lee Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea info_outline Choong-kun Lee, Jaekyung Cheon, Hong Jae Chon, Min Hwan Kim, Jin Won Kim, Myung Ah Lee, Hyung Soon Park, Myoung Joo Kang, Joung-Soon Jang, Hye Jin Choi Organizations Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea, Department of Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea, Severance Hospital, Yonsei University Health System, Seoul, South Korea, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea, St. Vincent's Hospital, Suwon, South Korea, Haeundae Paik Hospital, Busan, South Korea, Division of Hematology/Oncology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea, Yonsei Cancer Center, Seoul, South Korea Abstract Disclosures Research Funding Other Boryung Pharmaceutical, Celltrion, Korean Cancer Study Group Background: Biliary tract cancer (BTC), one of the most fatal cancers with limited treatment options, is generally rare in most high-income countries, but is relatively prevalent in South Korea. Recent genomic profilings have provided druggable molecular targets including HER2 amplification, which accounts for about 15% of total BTC patients. Trastuzumab is a humanized monoclonal antibody against HER2 with known efficacy in patients with HER2-positive breast and gastric cancer, and has not been tested prospectively in patients with HER2-positive BTC. The modified-FOLFOX regimen is currently being tested as a second-line therapy of BTC in phase III ABC-06 trial. This phase II study is investigating the combination of trastuzumab and modified-FOLFOX as second- or third-line treatment in HER2-postivie BTC. Methods: This study (KCSG-HB19-14; NCT04722133) is a phase II, multi-institutional, single arm trial to evaluate the efficacy and safety of trastuzumab plus modified-FOLFOX in gemcitabine/cisplatin refractory patients with HER2-positive BTC. The main inclusion criteria are HER2-positive (defined as IHC3+, or IHC2+/ISH+; ISH+ defined as HER2/CEP17 ≥2.0, or ERBB2 gene copy number ≥ 6.0 by NGS) BTC (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of vater cancer) patients who progressed on gemcitabine/cisplatin containing chemotherapy (one or two previous cytotoxic chemotherapy lines permitted), ECOG 0 or 1, and adequate organ function. Patients receive trastuzumab-pkrb 4mg/kg (after 6mg/kg load) D1, oxaliplatin 85mg/m 2 D1, leucovorin 200mg/m 2 D1, 5-FU 400mg/m 2 bolus D1, and 5-FU 2400mg/m 2 infusion D1-2 every 2 weeks until unacceptable toxicities or disease progression. The study has a Simon's two-stage design, with objective response rate (ORR) per RECIST v1.1 as primary endpoint. Secondary endpoints included progression-free survival, disease control rate, overall survival, safety, quality of life and correlative biomarker exploration. Additional patients were to be recruited if pre-specified thresholds for ORR are met at the first stage. The study will enroll up to 34 patients and is currently recruiting at eight sites in South Korea. As of February 2021, 16 patients have been enrolled. The pre-specified activity goal for the first stage of accrual was met; second stage accrual began in February 2021. Clinical trial information: NCT04722133