Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study

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

FIGURE 1

Pharmacokinetic profile of the TV ADC and free MMAE. Plasma concentrations of the ADC (A, C) and free MMAE (B, D) in plasma from patients in the dose escalation cohort (part 1; A, B) and the dose expansion cohort (part 2; C, D) for cycles 1 and 2. The gray dashed line represents the lower limit of quantitation. ADC, antibody–drug conjugate; MMAE, monomethyl auristatin E; TF‐ADC, tissue factor to antibody–drug conjugate; TV, tisotumab vedotin

FIGURE 2

Maximum percentage change in target lesions in patients in dose expansion phase (part 2). The best overall response was evaluated by the independent review. Data from 15 patients are shown. Two patients were not evaluable because they did not undergo postbaseline scans because of withdrawal (one death and one patient decision). The dashed line represents a 30% decrease. PD, progressive disease; PR, partial response; SD, stable disease

FIGURE 3

Time to response (TTR) and duration of response (DOR) in the five patients in dose expansion phase (part 2) who achieved a confirmed response. Response was assessed by independent review. One patient had one prior line of therapy in the recurrent or metastatic setting, and the others had two prior lines. All patients with two prior lines had received bevacizumab in combination with a chemotherapy doublet as first‐line systemic treatment. CR, complete response; PD, progressive disease; PR, partial response

FIGURE 4

Tumor membrane H‐score for tissue factor at baseline among patients in dose‐expansion phase (part 2) by best confirmed overall response. The lines within the boxes represent the median, whiskers extend to the most extreme observation within 1.5 times the interquartile range from the nearest quartile, X's represent the mean, and circles represent individual tumor samples. PR, partial response; PD, progressive disease; SD, stable disease