Phase II trial of nivolumab monotherapy and biomarker screening in patients with chemo‐refractory germ cell tumors
Takashi Kawahara, Koji Kawai, Takahiro Kojima, Yoshiyuki Nagumo, Shotarou Sakka, Shuya Kandori, Hiromitsu Negoro, Bryan J. Mathis, Kazushi Maruo, Kōji Miura, Noriaki Sakamoto, Nobuo Shinohara, Shinichi Yamashita, Kan Yonemori, Takeshi Kishida, Osamu Ukimura, Kazuo Nishimura, Yasuyuki Kobayashi, Hiroyuki Nishiyama
Abstract
OBJECTIVES: Germ cell tumors are highly susceptible to chemotherapy; however, there is a lack of established treatments for consistently relapsing germ cell tumor. Therefore, in this phase II study, we evaluated the efficacy and safety of nivolumab for relapsed germ cell tumor. METHODS: Seventeen adult patients (median age 34 years) with refractory primary germ cell tumor after second-line or higher chemotherapy were enrolled. Nivolumab was administered over 30 min at 240 mg/body every 2 weeks until disease progression or intolerable adverse event occurrence. The primary endpoint was the overall response rate. RESULT: We performed a biomarker analysis of programmed death ligand-1 expression and genomic sequencing. Tumor histology revealed nonseminoma and seminoma in 14 and three patients, respectively. Patients were pretreated with a median of three chemotherapy lines, and three patients received high-dose chemotherapy. The median number of nivolumab doses was 3 (range 2-46). One patient showed a partial response and three showed stable disease. Responses were durable in one patient with a partial response and one patient with stable disease (median 90 and 68 weeks, respectively). Nivolumab was well-tolerated, with only two Grade 3 adverse events observed. Programmed death ligand-1 expression was not associated with objective responses. Genomic sequencing revealed a high tumor mutation burden in a patient with a durable partial response. While a small subset of chemorefractory germ cell tumors may respond to nivolumab, programmed death ligand-1 is unreliable to measure response. CONCLUSIONS: Tumor mutation burden is a potential biomarker for future testing of germ cell tumor response.