Tisotumab Vedotin protocols have significant anti-tumor activity in all settings of metastatic cervical cancer


At a median follow-up of 13.0 months in the tisotumab vedotin / pembrolizumab cohort (n = 34), the ORR was 38% (n = 13; 95% CI, 22% to 56%), including 2 OR (6 %) and 11 PR (32%); there were 12 cases of SD (35%).

“Given the limited sample size, first-line tisotumab vedotin plus carboplatin and second- and third-line tisotumab vedotin plus pembrolizumab have shown encouraging and lasting anti-tumor activity in patients with cervical cancer. recurrent or metastatic uterus ”, said lead author of the study, Ignace B. Vergote, MD, PhD, Head of Department of Obstetrics and Gynecology and Gynecological Oncology, Catholic University of Louvain, in Belgium, in a virtual presentation of the data.

First-line platinum and taxane chemotherapy plus bevacizumab (Avastin), if eligible, improved survival in patients with recurrent or metastatic cervical cancer, but more effective and longer treatments sure are needed.

Tisotumab vedotin, an antibody-drug conjugate (ADC) that targets tissue factor, is being studied for the treatment of several solid tumors, including cervical cancer.

On April 9, 2021, the FDA granted priority review to Biologics License Application (BLA) for tisotumab vedotin as a potential treatment for patients with recurrent or metastatic cervical cancer with progressive disease under or after chemotherapy.2

The request was based on the results of the innovaTV 204 phase 2 trial (NCT03438396), which showed that 2 mg / kg of intravenous (IV) treatment with ADC given every 3 weeks resulted in an ORR of 24% and a median duration of response. (DOR) of 8.3 months in patients previously treated with recurrent or metastatic cervical cancer.3 In addition, the agent had a manageable security profile.

The recommended phase 2 dose for tisotumab vedotin in combination with pembrolizumab, carboplatin and bevacizumab in patients with recurrent or metastatic cervical cancer participating in innovaTV 205 was recently reported at the meeting. International Gynecologic Cancer Society Annual Global 2021.4

This review focuses on the carboplatin and pembrolizumab cohorts. In the carboplatin cohort, patients without previous systemic treatment for recurrent or metastatic cervical cancer received 2 mg / kg IV tisotumab vedotin every 3 weeks plus IV carboplatin at an area under the curve of 5 all every 3 weeks. In the pembrolizumab cohort, patients with recurrent or metastatic cervical cancer with disease progression during or after 1 or 2 previous systemic treatments received tisotumab vedotin 2 mg / kg IV every 3 weeks plus 200 mg pembrolizumab IV every 3 weeks.

ORR according to RECIST v1.1 criteria was used as the primary endpoint; secondary endpoints included adverse reactions (AEs) and laboratory parameters, DOR, response time, progression-free survival (PFS), overall survival (OS), and pharmacokinetic concentrations and anti- antibodies. drug associated with tisotumab vedotin.

Demographics and baseline clinical characteristics indicated that in the carboplatin and pembrolizumab cohorts, the median age was 51.0 years versus 47.0 years, respectively. The majority of patients in both cohorts had an ECOG performance index of 0, squamous histology and previous radiochemotherapy.

In the pembrolizumab cohort, 81.5% of patients (n = 22) were PD-L1 positive, and the majority of patients had received 1 line of prior treatment (n = 26; 74.3%) and prior treatment with bevacizumab (n = 18; 51.4%).

Additional results showed that in the tisotumab vedotin / carboplatin cohort, the median PFS was 9.5 months (95% CI, 4.0-not reached [NR]), and the median OS was NR (range: 0.8+ to 14.1+). The median DOR was 8.3 months (95% CI, 4.2-NR). The median time to response was 1.4 months (range 1.1-4.4).

The median duration of exposure was 4.9 months (range, 1-9) with tisotumab vedotin vs 4.1 months (range 1-9) with carboplatin. The median number of cycles initiated was 6.0 (range, 1-12) with tisotumab vedotin and carboplatin.

In the tisotumab vedotin / pembrolizumab cohort, the median PFS was 5.6 months (95% CI: 2.7-13.7) and the median OS was NR (range: 1.3-17.5 +) . The median DOR was 13.8 months (95% CI, 2.8-NR). The median time to response was 1.4 months (range 1.3-5.8).

The median duration of exposure was 4.1 months (range 1-16) with tisotumab vedotin vs 4.3 months (range 1-17) with pembrolizumab. The median number of cycles initiated was 6.0 (range, 1-21) with tisotumab vedotin and 6.0 months (range, 1-25) with pembrolizumab.

In terms of safety, in the tisotumab vedotin / carboplatin cohort, all patients had at least 1 on-treatment AEI (TIA); 97% (n = 32) of these events were related to tisotumab vedotin. Grade 3 or greater AEs occurred in 78.8% (n = 26) of patients; 57.6% (n = 19) of these events were related to tisotumab vedotin.

Serious AEs occurred in 42.4% of patients (n = 14); 15.2% (n = 5) of these events were related to tisotumab vedotin. No patient in the cohort had a fatal event.

In the tisotumab vedotin / pembrolizumab cohort, all patients had at least 1 TIA; 97.1% (n = 34) of these events were related to tisotumab vedotin. AEs of grade 3 or greater occurred in 74.3% (n = 26) of patients; 45.7% (n = 16) of these events were related to tisotumab vedotin.

Serious AEs occurred in 51.4% of patients (n = 18); 14.3% (n = 5) of these events were related to tisotumab vedotin. A fatal event was reported in the cohort but was not determined to be related to tisotumab vedotin.

AEs that occurred in approximately half of patients in both cohorts included ocular events, bleeding events, and peripheral neuropathy.

“These data support further research to evaluate additional combinations of tisotumab vedotin as interventions in recurrent or metastatic cervical cancer. The dose extension cohort of tisotumab vedotin and pembrolizumab in first-line recurrent or metastatic cervical cancer in this study is being evaluated and will be reported at a future medical meeting, ”a Vergote concluded.

The references

  1. Vergote IB, Monk BJ, O’Cearbhaill RE, et al. Tisotumab vedotin (TV) + first-line carboplatin (carbo) (1L) or + pembrolizumab (pembro) in previously treated recurrent or metastatic cervical cancer (r / mCC) (2L / 3L): intermediate results of ENGOT-Cx8 / GOG -3024 / innovaTV 205 study. Presented at: ESMO 2021 Congress; September 16-21, 2021; virtual. Abstract 723MB.
  2. Seagen and Genmab announce US FDA acceptance of a priority review of the biologic license application for tisotumab vedotin for patients with recurrent or metastatic cervical cancer. Press release. April 9, 2021. Accessed September 19, 2021. https://bit.ly/3s6I7AL
  3. Coleman RL, Lorusso D, Gennigens C, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer: results of the innovaTV 204 / GOG-3023 / ENGOT-cx6 phase 2 study. Anne Oncol. 2020; 31 (suppl 4): S1162-S1163. doi: 10.1016 / j.annonc.2020.08.2262
  4. Monk BJ, Van Gorp T, Lorusso D, et al. Tisotumab vedotin + bevacizumab or pembrolizumab or carboplatin in relapsed / metastatic cervical cancer: results from the phase 1b / 2 ENGOT-Cx8 / GOG-3024 / innovaTV 205 dose escalation study. Presented at the 2021 IGCS Annual Global Meeting; August 30-September 2, 2021; virtual. Plenary 5.


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