Tisotumab Vedotin Continues to Show Survival Benefits in Recurrent Cervical Cancer

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Tisotumab vedotin-tftv (Tivdak) as a second- or third-line treatment led to improved overall survival (OS) vs investigator’s choice of chemotherapy in patients with cervical cancer, according to a prespecified interim analysis of the phase 3 innovaTV 301/ENGOT-cx12/GOG-3057 study (NCT04697628).^1,2

In the tisotumab vedotin arm, OS was 11.5 months (95% CI, 9.8-14.9) vs 9.5 months in the chemotherapy arm (95% CI, 7.9-10.7), resulting in a 30% lower risk of death with tisotumab vedotin (HR, 0.70; 95% CI, 0.54-0.89; 2-sided P =.004). Progression-free survival (PFS) was 4.2 months (95% CI, 4.0-4.4) with tisotumab vedotin vs 2.9 months (95% CI, 2.6-3.1) with chemotherapy (HR, 0.67; 95% CI, 0.54-0.82; 2-sided P <.001). In the tisotumab vedotin arm, the confirmed objective response rate (ORR) was 17.8% compared with 5.2% with chemotherapy (odds ratio, 4.0; 95% CI, 2.1-7.6; 2-sided P <.001).

Regarding safety, 98.4% of patients in the tisotumab vedotin arm and 99.2% in the chemotherapy arm experienced at least 1 adverse event (AE) during treatment. Grade 3 or higher AEs were reported in 52.0% and 62.3% of patients in the tisotumab vedotin and chemotherapy arms, respectively.

“By doing this trial, we came up with a treatment option that we didn't have for these patients, and something that's different from checkpoint inhibition, immunotherapy, and chemotherapy. It uses a technology called an antibody-drug conjugate, an ADC, and it is novel in this disease,” said Brian Slomovitz, MD, gynecologic oncologist, director of gynecologic oncology, Mount Sinai Medical Center, Miami Beach, Florida, and investigator of the innovaTV 301 trial, in an interview with Targeted Oncology^TM.

About Tisotumab Vedotin

Tisotumab vedotin is a targeted ADC therapy composed of a tissue factor (TF)-directed monoclonal antibody covalently inked to monomethyl auristatin E, a microtubule-disrupting agent.¹ TF expression is higher in several solid tumors, including cervical cancer.

While tisotumab vedotin as a monotherapy has shown significant promise, it is also being explored in combinations, including with the immune checkpoint inhibitor pembrolizumab (Keytruda). In the innovaTV 205 study (NCT03786081), tisotumab vedotin plus pembrolizumab in the first-line setting delivered an ORR of 40.6% (95% CI, 23.7%-59.4), and the median duration of response was not reached.³

In April 2024, the FDA granted full approval to tisotumab vedotin for the treatment of advanced cervical cancer.⁴ The innovaTV 301 trial supported this approval. Data was presented at the 2023 European Society for Medical Oncology (ESMO) Annual Congress. Here, 6-month PFS rates at 6 months were 30.4% and 18.9% with tisotumab vedotin vs chemotherapy, respectively.

REFERENCES:

1. Second- or third-line treatment with tisotumab vedotin results in greater efficacy than chemotherapy in patients with recurrent cervical cancer. News release. European Society for Medical Oncology. July 12, 2024. Accessed July 17, 2024. https://tinyurl.com/yc5586me

2. Vergote I, González-Martín A, Fujiwara K, et al. Tisotumab vedotin as second- or third-line therapy for recurrent cervical cancer. N Engl J Med. 2024;391:44-55. doi:10.1056/NEJMoa2313811

3. Vergote I, Van Nieuwenhuysen E, O’Cearbhaill R, et al. Tisotumab vedotin in combination with carboplatin, pembrolizumab, or bevacizumab in recurrent or metastatic cervical cancer: results from the innovaTV 205/GOG-3024/ENGOT-cx8 study. J Clin Oncol. 2024;41:5536-5549. doi:10.1200/JCO.23.00720

4. FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. News release. FDA. April 29, 2024. Accessed July 17, 2024. https://tinyurl.com/2s3h66ke