A phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with solid cancers harboring HER2 amplification (JUPITER trial).

person Ryo Kudo Tokyo Medical and Dental University hospital, Bunkyo-Ku, Japan info_outline Ryo Kudo, Toshio Kubo, Yukiko Mori, Yohei Harada, Hidekazu Shirota, Hideyuki Hayashi, Masayuki Kano, Yasushi Shimizu, Eri Ishibashi, Hirotoshi Akita, Hisahiro Matsubara, Hiroshi Nishihara, Chikashi Ishioka, Naoko Sueoka-Aragane, Manabu Muto, Shinichi Toyooka, Ukihide Tateishi, Akihiro Hirakawa, Satoshi Miyake, Sadakatsu Ikeda

Authors person Ryo Kudo Tokyo Medical and Dental University hospital, Bunkyo-Ku, Japan info_outline Ryo Kudo, Toshio Kubo, Yukiko Mori, Yohei Harada, Hidekazu Shirota, Hideyuki Hayashi, Masayuki Kano, Yasushi Shimizu, Eri Ishibashi, Hirotoshi Akita, Hisahiro Matsubara, Hiroshi Nishihara, Chikashi Ishioka, Naoko Sueoka-Aragane, Manabu Muto, Shinichi Toyooka, Ukihide Tateishi, Akihiro Hirakawa, Satoshi Miyake, Sadakatsu Ikeda Organizations Tokyo Medical and Dental University hospital, Bunkyo-Ku, Japan, Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan, Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, Saga University, Saga, Japan, Tohoku University, Sendai, Japan, Division of Clinical Cancer Genomics, Hokkaido University Hospital, Sapporo, Japan, Chiba University, Chiba, Japan, Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan, Tokyo Medical and Dental University, Tokyo, Japan, Deparment of Medical Oncology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan, Genomics Unit, Keio Cancer Center, Keio University School of Medicine, Tokyo, Japan, Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan, Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama, Japan, Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, University of California, San Diego, La Jolla, CA Abstract Disclosures Research Funding Other Government Agency Japanese Agency for Medical Research and Development Background: The human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. However, even if an actionable gene alteration is found, the incidence of HER2 amplification in these cancers is less than 5%. Despite its considerable therapeutic potential, the evidence is not yet mature enough for use as treatment in clinical practice. To address this unmet clinical need, we have designed an organ-agnostic basket trial, which covers a variety of solid cancers harboring HER2 amplification. Methods: JUPITER trial is a Japanese multicenter, single-arm, phase 2 basket study of combination therapy with trastuzumab and pertuzumab. Patients with solid cancers harboring HER2 amplification, who have progressed with standard treatment, or rare cancers for which there is no standard treatment, are eligible. Types of cancer include bile duct, urothelial, uterine, ovarian, and other solid cancers that HER2 amplification is detected by comprehensive genomic profiling using next-generation sequencing technology. Target sample size is 38. All enrolled patients receive combination therapy with trastuzumab and pertuzumab every 3 weeks until disease progression, unacceptable toxicity, death, or withdrawal of informed consent. Response assessment using RECIST version 1.1 is performed at weeks 9 and 17, followed by every 12 weeks. The primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, duration of response, and safety. In total, 40 patients were enrolled by June 2020. Data fix is scheduled in September 2021. Trial registration: jRCT2031180150 Clinical trial information: jRCT2031180150.