FDA Grants Full Approval to Tisotumab Vedotin-tftv for Recurrent, Metastatic Cervical Cancer

Following its accelerated approval in September 2021, the FDA has granted full approval to tisotumab vedotin-tftv (Tivdak; Pfizer and Genmab) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.¹

“As a treating physician, it is encouraging to see overall survival data among these patients and a manageable safety profile with tisotumab vedotin,” said Brian Slomovitz, MD, Director of Gynecologic Oncology and Co-Chair of the Cancer Research Committee at Mount Sinai Medical Center in Miami Beach, Florida, in the news release. “Treatment options for patients with advanced or recurrent cervical cancer are limited. The 5-year survival rate for patients who have metastatic disease at diagnosis is less than 20% in the US.”¹

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Tisotumab vedotin-tftv is the first antibody-drug conjugate (ADC) to demonstrate positive overall survival (OS) data in patients with previously treated recurrent or metastatic cancer, according to a news release. The conversion to full approval from accelerated approval is based on data from the global phase 3 innovaTV 301 clinical trial, which demonstrated OS benefit with tisotumab vedotin-tftv compared with chemotherapy.¹

“Recurrent or metastatic cervical cancer is a particularly devastating and mostly incurable disease, and patients are in need of survival-extending treatment options,” said Chris Boshoff, MD, PhD, Chief Oncology Officer and Executive Vice President at Pfizer, in the news release. “Today’s full approval by the FDA reinforces the important role of Tivdak for these patients, as the first antibody-drug conjugate with statistically significant prolonged overall survival data.”¹

According to study results published in the Annals of Oncology, eligible patients in innovaTV 301 were randomized 1:1 to either tisotumab vedotin-tftv monotherapy or investigator’s choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary end point was OS and key secondary end points included progression-free survival (PFS) and confirmed overall response rate (ORR) by investigator.²

A total of 502 patients were randomized (253 to tisotumab vedotin-tftv and 249 to chemotherapy). The median survival follow-up was 10.8 months, the median age was 50 years, and the arms were balanced for demographics and disease characteristics. Additionally, 63.9% and 27.5% of patients had prior bevacizumab and prior anti-PD-(L)1 therapy, respectively.²

The investigators found that patients in the tisotumab vedotin-tftv arm had a 30% reduction in risk of death vs chemotherapy (HR 0.70; 95% CI 0.54-0.89; P=0.0038), with a significantly longer median OS or 11.5 months (95% CI 9.8-14.9) vs 9.5 months in the chemotherapy arm (95% CI 7.9-10.7). PFS was also superior in the tisotumab vedotin-tftv arm (HR:0.67 [95% CI, 0.54-0.82]; P<0.0001). Confirmed ORR was 17.8% in the tisotumab vedotin-tftv arm and 5.2% in the chemotherapy arms (odds ratio: 4.0; 95% CI, 2.1-7.6; P<0.0001).²

“The full FDA approval of Tivdak represents a significant achievement for women with recurrent and metastatic cervical cancer, reinforcing Tivdak as a treatment option that has proven to extend survival in patients whose disease has advanced after initial treatments,” said Jan van de Winkel, PhD, CEO of Genmab, in the news release. “This milestone underscores the importance of our ongoing clinical development program to assess the full potential of tisotumab vedotin as a treatment option in other indications.”¹

Most patients experienced at least 1 treatment-related adverse event (AE), including 87.6% of patients in the tisotumab vedotin-tftv arm (grade ≥3: 29.2%) and 85.4% in the chemotherapy arm (grade ≥3: 45.2%). AEs were consistent with the known safety profile of tisotumab vedotin-tftv, including ocular, peripheral neuropathy, and bleeding AEs.²

Tisotumab vedotin-tftv includes a Boxed Warning for ocular toxicity as well as warnings and precautions for peripheral neuropathy, hemorrhage, pneumonitis, severe cutaneous adverse reactions, and embryo-fetal toxicity. The most common AEs in innovaTV 301, including laboratory abnormalities, in patients receiving tisotumab vedotin-tftv were decreased hemoglobin (41%), peripheral neuropathy (38%), conjunctival adverse reactions (37%), increased aspartate aminotransferase (34%), nausea (33%), increased alanine aminotransferase (30%), fatigue (28%), decreased sodium (27%), epistaxis (26%), and constipation (25%).¹

“These is a high unmet need for more treatment options that have demonstrated survival benefit in the contemporary treatment landscape,” Slomovitz said in the news release. “The approval of tisotumab vedotin brings us a step closer to fulfilling that need.”¹

References

1. FDA Grants Full Approval for Tivdak to Treat Recurrent or Metastatic Cervical Cancer. News release. Pfizer. April 29, 2024. Accessed April 30, 2024. https://www.pfizer.com/news/press-release/press-release-detail/fda-grants-full-approval-tivdakr-treat-recurrent-or

2. Vergote IB, Martin AG, Fujiwara K, Kalbacher E, et al. LBA9 innovaTV 301/ENGOT-cx12/GOC-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 Onc. 2023;34(2):S1276-S1277. doi:10.1016/j.annonc.2023.10.029