Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study
Kan Yonemori, Yasutoshi Kuboki, Kosei Hasegawa, Takashi Iwata, Hidenori Kato, Kazuhiro Takehara, Yasuyuki Hirashima, Hisamori Kato, Chaitali Passey, Jeppe Klint Buchbjerg, Jeffrey R Harris, Camilla Mondrup Andreassen, Leonardo Nicacio, Ibrahima Soumaoro, Keiichi Fujiwara, Kan Yonemori, Yasutoshi Kuboki, Kosei Hasegawa, Takashi Iwata, Hidenori Kato, Kazuhiro Takehara, Yasuyuki Hirashima, Hisamori Kato, Chaitali Passey, Jeppe Klint Buchbjerg, Jeffrey R Harris, Camilla Mondrup Andreassen, Leonardo Nicacio, Ibrahima Soumaoro, Keiichi Fujiwara
Abstract
New treatments, particularly second-line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody-drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single-arm, open-label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non-Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1-2 prior lines of therapy. In part 1, no dose-limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment-emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non-Japanese patients.
Keywords: female; recurrence; thromboplastin; tisotumab vedotin; uterine cervical neoplasms.
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Figures
References
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394‐424. doi:10.3322/caac.21492
- World Health Organization . Cancer Fact Sheets: Cervical Cancer.
- Yamagami W, Nagase S, Takahashi F, et al. Clinical statistics of gynecologic cancers in Japan. J Gynecol Oncol. 2017;28(2):e32. doi:10.3802/jgo.2017.28.e32
- Noguchi T, Zaitsu M, Oki I, et al. Recent increasing incidence of early‐stage cervical cancers of the squamous cell carcinoma subtype among young women. Int J Environ Res Public Health. 2020;17(20):7401. doi:10.3390/ijerph17207401
- Utada M, Chernyavskiy P, Lee WJ, et al. Increasing risk of uterine cervical cancer among young Japanese women: comparison of incidence trends in Japan, South Korea and Japanese‐Americans between 1985 and 2012. Int J Cancer. 2019;144(9):2144‐2152. doi:10.1002/ijc.32014
- National Cancer Center Cancer Information Service . Cancer type statistics: cervix. Accessed March 2022.
- Kitagawa R, Katsumata N, Shibata T, et al. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open‐label randomized phase III trial JCOG0505. J Clin Oncol. 2015;33(19):2129‐2135. doi:10.1200/JCO.2014.58.4391
- Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370(8):734‐743. doi:10.1056/NEJMoa1309748
- Ebina Y, Mikami M, Nagase S, et al. Japan Society of Gynecologic Oncology guidelines 2017 for the treatment of uterine cervical cancer. Int J Clin Oncol. 2019;24(1):1‐19. doi:10.1007/s10147-018-1351-y
- US Food and Drug Administration . Keytruda [package insert]. Merck Sharp Dohme. Accessed May 2022.
- Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385(20):1856‐1867. doi:10.1056/NEJMoa2112435
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) . Cervical Cancer. Accessed May 2022. .
- Safety and efficacy of tisotumab vedotin monotherapy & in combination with other cancer agents in subjects with cervical cancer. Accessed March 2022.
- Efficacy and safety study of tisotumab vedotin for patients with solid tumors (innovaTV 207). Accessed March 2022.
- Breij EC, de Goeij BE, Verploegen S, et al. An antibody‐drug conjugate that targets tissue factor exhibits potent therapeutic activity against a broad range of solid tumors. Cancer Res. 2013;74(4):1214‐1226. doi:10.1158/0008-5472.CAN-13-2440
- de Goeij BE, Satijn D, Freitag CM, et al. High turnover of tissue factor enables efficient intracellular delivery of antibody‐drug conjugates. Mol Cancer Ther. 2015;14(5):1130‐1140. doi:10.1158/1535-7163.MCT-14-0798
- Versteeg HH, Spek CA, Peppelenbosch MP, Richel DJ. Tissue factor and cancer metastasis: the role of intracellular and extracellular signaling pathways. Mol Med. 2004;10(1–6):6‐11. doi:10.2119/2003-00047.versteeg
- Zhao X, Cheng C, Gou J, et al. Expression of tissue factor in human cervical carcinoma tissue. Exp Ther Med. 2018;16(5):4075‐4081. doi:10.3892/etm.2018.6723
- Cocco E, Varughese J, Buza N, et al. Expression of tissue factor in adenocarcinoma and squamous cell carcinoma of the uterine cervix: implications for immunotherapy with hI‐con1, a factor VII‐IgGFc chimeric protein targeting tissue factor. BMC Cancer. 2011;11:263. doi:10.1186/1471-2407-11-263
- Hong DS, Concin N, Vergote I, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer. Clin Cancer Res. 2020;26(6):1220‐1228. doi:10.1158/1078-0432.CCR-19-2962
- Coleman RL, Lorusso D, Gennigens C, et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG‐3023/ENGOT‐cx6): a multicentre, open‐label, single‐arm, phase 2 study. Lancet Oncol. 2021;22(5):609‐619. doi:10.1016/S1470-2045(21)00056-5
- US Food and Drug Administration Tivdak™ (tisotumab verdotin‐tftv) [package insert]. Seagen Inc. Updated September 2021. Accessed October 6, 2021.
- Pharmaceuticals and Medical Devices Agency (PMDA) Basic principles on Global Clinical Trials. Accessed July 12, 2021.
Source: PubMed