Tisotumab Vedotin Gains Full FDA Approval in Advanced Cervical Cancer

• Tisotumab vedotin-tftv (Tivdak) was granted full approval by the FDA for patients with recurrent or metastatic cervical cancer whose disease has progressed on or after first-line therapy.
• The antibody-drug conjugate was studied in the phase 3 innovaTV 301 trial (NCT04697628).
• Previously in September 2021, tisotumab vedotin was granted accelerated approval for the treatment of metastatic cervical cancer.

The FDA has granted full approval to tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer whose disease has progressed on or after chemotherapy.¹

Results from the phase 3 innovaTV 301 trial support this FDA approval. During the 2023 European Society of Medical Oncology Congress, treatment with tisotumab led to a 30% reduction in the risk of death vs investigator’s choice of chemotherapy as a second- or third-line treatment among those in the intent-to-treat population.

The median overall survival (OS) was 11.5 months (95% CI, 9.8-14.9) at a median follow-up of 10.8 months (95% CI, 10.3-11.6) with tisotumab compared with 9.5 months (95% CI, 7.9-10.7) with chemotherapy (HR, 0.70, 95% CI, 0.54-0.89; P =.0038). At 12 months, the OS rates observed between the 2 arms were 48.7% and 35.3%, respectively.²

With tisotumab vedotin, the median progression-free survival (PFS) was 4.2 months (95% CI, 4.0-4.4) compared with 2.9 months (95% CI, 2.6-3.1) with chemotherapy (HR, 0.67; 95% CI, 0.54-0.82; P <.0001). Further, the PFS rates at 6 months were 30.4% and 18.9%, respectively, with tisotumab vs chemotherapy.

“In oncology care, we want to find the best treatment that treats all patients. But without doing that, we want to take positive steps. This is a tremendous step in the right direction,” Brian Slomovitz, MD, gynecologic oncologist, director of gynecologic oncology, Mount Sinai Medical Center, Miami Beach, Florida, and primary investigator of the innovaTV 301 trial, said in an interview with Targeted OncologyTM.

About Tisotumab Vedotin and innovaTV 301

Tisotumab was previously granted accelerated approval from the FDA for the treatment of patients with metastatic cervical cancer in September 2021. In January 2024, the FDA accepted the supplemental biologics license application for tisotumab, which aimed to convert the accelerated approval of the agent to full approval for patients with recurrent or metastatic cervical cancer whose disease has progressed on or after first-line therapy.

Enrollment in the phase 3 innovaTV 301 trial was open to patients who received a diagnosis of recurrent or metastatic cervical cancer, had documented disease progression on or after doublet chemotherapy with or without bevacizumab (Avastin) and an anti-PD(L)1 agent if eligible and available, measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and exposure to no more than 2 prior lines of therapy.³

The study randomized patients 1:1 to receive 2.0 mg/kg of intravenous tisotumab vedotin every 3 weeks (n = 253) or investigator’s choice of chemotherapy (n = 249), which could have included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary end point was OS with secondary end points of PFS, ORR, and safety.

REFERENCES:

1. FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. News release. US FDA. April 29, 2024. Accessed April 29, 2024. https://tinyurl.com/2s3h66ke

2. Tivdak supplemental biologics license application accepted for priority review by FDA for patients with recurrent or metastatic cervical cancer. News release. Pfizer. January 9, 2024. Accessed March 29, 2024. http://tinyurl.com/mud6nb9n

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