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◥Purpose: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623).Patients and Methods: Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity.Results: Of the 55 patients, 51% had received !2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab þ doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%À37%]. Median duration of response (DOR) was 4.2 months (range: 1.0 þ À9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%À43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%À35%), median DOR of 6.0 months (range: 1.0 þ À9.7), and 6-month PFS rate of 40% (95% CI: 24%À55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed.Conclusions: Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer.Cervical cancer is a common cancer in women, with an estimated 570,000 new cases globally in 2018, and represents the third leading cause of cancer-related death in women worldwide (1). Approximately 15,500 and 61,000 new cases of cervical cancer were estimated in North America and in Europe in 2018, respectively, resulting in approximately 5,800 and 25,800 deaths (2). Recurrent or metastatic cervical cancer has a poor prognosis, with a 5-year survival rate of 17% (3). Bevacizumab and doublet chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) were adopted as first-line (1L) standard-ofcare therapy for recurrent or metastatic cervical cancer in the past 5 years (4-6). However, nearly all patients relapse after 1L treatment, and single-institution experiences indicate that the percentage of patients who receive a second-line (2L) therapy varies (30%-70%) as many patients die before receiving treatment (7,8).Available 2Lþ therapies for recurrent or metastatic cervical cancer are characterized by low response rates (5,6). Before adoption of bevacizumab plus doublet chemotherapy in 1L, therapies administered in the 2Lþ setting reported response rates in the range of 4.5% to 15%, with median s...

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Purpose Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma. Patients and Methods A total of 71 eligible patients were randomly assigned to receive etirinotecan pegol 145 mg/m2 every 14 or 21 days until progression or unacceptable adverse events (AEs). The primary end point was objective response rate (ORR) by RECIST (version 1.0). Secondary end points included response by Gynecologic Cancer Intergroup criteria, duration of ORR, progression-free survival (PFS), and overall survival (OS). Results The overall confirmed ORR was 20% (95% CI, 10% to 30%): 20% for once every 14 days, and 19% for once every 21 days. Median response duration was 4.1 months for once every 14 days and 4.0 months for once every 21 days. Median PFS for every 14 and every 21 days was 4.1 and 5.3 months, respectively, and median OS was 10.0 and 11.7 months, respectively. Etirinotecan pegol was well tolerated, with the most common grade 3 to 4 AEs being dehydration (24%) and diarrhea (23%). Diarrhea, dehydration, nausea, and neutropenia were less frequent with the schedule of once every 21 days than with that of once every 14 days. Conclusion Both schedules of etirinotecan pegol showed activity in patients with heavily pretreated ovarian cancer, with encouraging ORR and PFS rates. The schedule of once every 21 days was better tolerated and had slightly longer PFS and OS rates. The treatment schedule of etirinotecan pegol 145 mg/m2 once every 21 days was selected for the expanded phase II study and is preferred for future phase III studies. These findings provide support to directly compare etirinotecan pegol versus one of the approved drugs (eg, pegylated liposomal doxorubicin or topotecan) in platinum-resistant ovarian cancer.