FDA Approval Sought for Tisotumab Vedotin in Recurrent or Metastatic Cervical Cancer

February 10, 2021 - A biologics license application has been submitted to the FDA for the accelerated approval of the antibody-drug conjugate tisotumab vedotin for use in patients with recurrent or metastatic cervical cancer that has progressed on or following chemotherapy.

A biologics license application (BLA) has been submitted to the FDA for the accelerated approval of the antibody-drug conjugate (ADC) tisotumab vedotin for use in patients with recurrent or metastatic cervical cancer that has progressed on or following chemotherapy.1

The application is based on data from the phase 2 innovaTV 204 trial (NCT03438396), in which the ADC induced an objective response rate (ORR) of 24% (95% CI, 15.9%-33.3%) in patients with recurrent or metastatic cervical cancer who previously received doublet chemotherapy and bevacizumab (Avastin).2

The ORR included a complete response rate of 7%, a partial response rate of 17%, and a median duration of response (DOR) of 8.3 months (95% CI, 4.2–not reached). Moreover, the median time to response (TTR) with tisotumab vedotin was 1.4 months (range, 1.1-5.1) with activity reported within the first 2 treatment cycles.

“The BLA submission is an important step toward our goal of improving the lives of women with recurrent or metastatic cervical cancer,” Jan van de Winkel, PhD, chief executive officer of Genmab, stated in a press release. “We believe, if approved, tisotumab vedotin as monotherapy has the potential to become an important treatment option for women with recurrent or metastatic cervical cancer, who have disease progression on or after chemotherapy.”

In the single-arm, multicenter, phase 2 innova TV 204 trial, a total of 101 previously treated patients with recurrent and/or metastatic cervical cancer received intravenous tisotumab vedotin at a dose of 2.0 mg/kg every 3 weeks until progressive disease or intolerable toxicity.

To be eligible for participation, patients had to have recurrent or extrapelvic metastatic disease, experienced disease progression during or after doublet chemotherapy with bevacizumab (if eligible), had previously received 2 or fewer systemic therapies, and have had an ECOG performance status of 0 to 1.

The primary end point of the trial was ORR in accordance with RECIST v1.1 criteria and independent imaging review committee (IRC). Key secondary end points comprised ORR per investigator assessment and RECIST, overall survival (OS), and safety. DOR, TTR, and progression-free survival (PFS) per IRC and investigator, served as additional end points. Investigators also evaluated biomarkers and health-related quality of life with the treatment.

The median age of patients on the trial was 50 years and the majority, or 95%, were white. Fifty-eight percent of patients had an ECOG performance status of 0. Sixty-eight percent of patients had squamous cell carcinoma, 27% had adenocarcinoma, and 5% had adenosquamous carcinoma. Almost all patients, or 94%, had extrapelvic metastatic disease at baseline.

Moreover, 54% of participants had previously received cisplatin plus radiation therapy and 70% had received 1 prior line of systemic treatment for recurrent or metastatic disease. Moreover, 63% of patients previously received bevacizumab and doublet chemotherapy as frontline treatment and 56% did not respond to their last systemic treatment.

Patients received treatment for a median duration of 4.2 months at a median of 6 doses; a high dose intensity of 95.9% was reported with the ADC. Four patients continued to receive treatment, while 65% of patients discontinued because of radiographic progression. Thirteen percent of patients stopped treatment due to toxicities, 8% due to clinical progression, 5% due to withdrawn consent, 4% because of death, and 1% per investigator decision.

Additional data presented during the 2020 ESMO Virtual Congress demonstrated that 4% of those who received the ADC achieved disease stability while 24% experienced disease progression per IRC. Seventy-nine percent of participants also experienced a reduction in target lesions.

Notably, clinically meaningful responses were experienced irrespective of tumor histology, lines of previous treatment, responses to previous systemic treatment, and whether frontline bevacizumab/doublet chemotherapy was received. Responses were also observed irrespective of membrane TF expression level.

The median PFS reported with the ADC was 4.2 months, while the OS was 12.1 months. The PFS rate at 6 months was 30%, while the OS rate at this time point was 79%.

The agent was found to have a manageable toxicity profile. The most frequently experienced toxicities associated with the ADC included alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (24%), dry eye (23%), and myalgia (15%), among others.

Most of the toxicities were determined to be just grade 1 or 2 in severity, although 28% of participants experienced effects that were grade 3/4. Of a total of 4 patients who died, 1 was because of septic shock that was determined to be related to tisotumab vedotin.

Toxicities of interest included ocular toxicity, bleeding, and peripheral neuropathy.

“In the pivotal phase 2 study, tisotumab vedotin induced clinically meaningful and durable responses in this difficult-to-treat cervical cancer patient population, with a manageable and tolerable safety profile,” Roger Dansey, MD, chief medical officer at Seagen, added in the release. “Today’s submission marks an important milestone for tisotumab vedotin and a potential advance for patients with recurrent or metastatic cervical cancer for whom there is a high unmet need for effective new therapies.


  1. Genmab and Seagen submit tisotumab vedotin biologics license application to the US FDA for patients with recurrent or metastatic cervical cancer. News release. Genmab A/S and Seagen Inc. February 10, 2021. Accessed February 10, 2021. http://bit.ly/3phVk8x.
  2. Coleman RL, Lorusso D, Gennigens C, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer: results from the phase 2 innovaTV 204/GOG-3023/ENGOT-cx6 study. Ann Oncol. 2020;31(suppl 4):S1162-S1163. doi:10.1016/j.annonc.2020.08.2262