FDA Approves Tisotumab Vedotin for Recurrent or Metastatic Cervical Cancer

The FDA has granted full approval to tisotumab vedotin-tftv (Tivdak) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.¹

The regulatory decision was supported by data from the phase 3 innovaTV 301 trial (NCT04697628), which showed that patients treated with tisotumab vedotin (n = 253) experienced a median overall survival (OS) of 11.5 months (95% CI, 9.8-14.9) compared with 9.5 months (95% CI, 7.9-10.7) for patients treated with chemotherapy (n = 249; HR, 0.70; 95% CI, 0.54-0.89; P = .0038). Additionally, the median progression-free survival (PFS) was 4.2 months (95% CI, 4.0-4.4) in the tisotumab vedotin arm vs 2.9 months (95% CI, 2.6-3.1) in the chemotherapy arm (HR, 0.67; 95% CI, 0.54-0.82; P <.0001).

Previously, in September 2021, the FDA granted accelerated approval to tisotumab vedotin for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, based on data from the phase 2 innovaTV 204 trial (NCT03438396).²

The phase 3, global, open-label, randomized innovaTV 301 trial evaluated the agent vs investigator's choice of chemotherapy in patients with recurrent or metastatic cervical cancer who experienced disease progression on or after a chemotherapy doublet with or without bevacizumab (Avastin) and an anti–PD-1 or –PD-L1 agent, if eligible and applicable.³

No more than 2 prior lines of therapy were permitted. Patients also needed to have measurable disease per RECIST v1.1 criteria and an ECOG performance status of 0 or 1.

Patients were randomly assigned 1:1 to receive 2.0 mg/kg of tisotumab vedotin once every 3 weeks or investigator's choice of chemotherapy, which consisted of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.

OS served as the trial's primary end point. Key secondary end points included PFS, overall response rate (ORR), and safety.

Additional data showed the 12-month OS rate was 48.7% for the tisotumab vedotin arm vs 35.3% for the chemotherapy arm. The 6-month PFS rates were 30.4% and 18.9%, respectively.

Tisotumab vedotin elicited an ORR of 17.8% (95% CI, 13.3%-23.1%) compared with 5.2% (95% CI, 2.8%-8.8%) for chemotherapy (odds ratio, 4.0; 95% CI, 2.1-7.6; P <.0001). In the experimental arm, the complete response, partial response, stable disease, and progressive disease rates were 2.4%, 15.4%, 58.1%, and 18.2%, respectively. Those respective rates were 0%, 5.2%, 53.0%, and 29.7% in the chemotherapy arm.

The disease control rate was 75.9% (95% CI, 70.1%-81.0%) for tisotumab vedotin vs 58.2% (95% CI, 51.8%-64.4%) for chemotherapy. The median duration of response was 5.3 months (95% CI, 4.2-8.3) and 5.7 months (95% CI, 2.8–not reached) for tisotumab and chemotherapy, respectively.

The most common adverse effects reported in at least 25% of patients treated with tisotumab vedotin included decreased hemoglobin, peripheral neuropathy, conjunctival adverse reactions, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, fatigue, decreased sodium, epistaxis, and constipation.¹

References

1. FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. FDA. April 29, 2024. Accessed April 29, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer
2. FDA grants accelerated approval to tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. FDA. September 20, 2021. Accessed April 29, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer
3. Vergote IB, Gonzalez Martin A, Fujiwara K, et al. innovaTV 301/ENGOT-cx12/GOG-3057: A global, randomized, open-label, phase III study of tisotumab vedotin vs investigator’s choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer. Ann Oncol. 2023;34(suppl 2):S1276-S1277. doi:10.1016/j.annonc.2023.10.029