Tisotumab Vedotin Improves Survival Vs Chemo in Recurrent Cervical Cancer

The FDA previously granted accelerated approval to tisotumab vedotin as a treatment for those with previously treated recurrent or metastatic cervical cancer in September 2021.

Treatment with tisotumab vedotin-tftv (Tivdak) resulted in an improvement in overall survival (OS) compared with chemotherapy in patients with recurrent or metastatic cervical cancer previously treated with first-line therapy, according to a press release on findings from the interim analysis of the phase 3 innovaTV 301 trial (NCT04697628).¹

An assessment by the Independent Data Monitoring Committee highlighted that the OS benefit following treatment with tisotumab vedotin reached the trial’s pre-specified efficacy threshold. Additionally, investigators reported statistically significant improvements in the tisotumab vedotin arm with respect to investigator-assessed progression-free survival (PFS) and objective response rate (ORR). Tisotumab vedotin did not produce any new safety signals in the trial.

The FDA previously granted accelerated approval to tisotumab vedotin as a treatment for those with previously treated recurrent or metastatic cervical cancer in September 2021.² Supporting data for the accelerated approval came from the phase 2 innovaTV 204 trial (NCT03438396), in which investigators reported an ORR of 24.0% (95% CI, 15.9%-33.3%) in patients who were treated with tisotumab vedotin. Developers intend to confirm the benefits of tisotumab vedotin that were highlighted at the time of the accelerated approval with data from the innovaTV 301 trial.

Investigators will present results from the innovaTV 301 trial at a future medical meeting and discuss their findings with regulatory authorities.

“[Tisotumab vedotin] is the only [FDA]-approved therapy in second-line recurrent or metastatic cervical cancer regardless of biomarker status, tumor histology and prior therapy,” Roger Dansey, MD, president of Research and Development and chief medical officer at Seagen, said in the press release.¹ “Demonstrating a survival benefit with the results of innovaTV 301 is a critical milestone in our efforts to ensure more adults living with advanced cervical cancer have an approved treatment option.”

Investigators of the international, open-label, randomized phase 3 innovaTV 301 trial assessed tisotumab vedotin vs investigator’s choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed in patients with metastatic or recurrent cervical cancer. Patients were randomly assigned to receive 2.0 mg/kg of tisotumab vedotin every 3 weeks or chemotherapy.

The trial’s primary end point was OS. Secondary end points included PFS per RECIST v1.1 criteria, ORR, time to response, duration of response, adverse effects, and health-related quality of life.

Patients 18 years and older with disease progression during or after treatment with a standard-of-care systemic chemotherapy doublet or platinum-based therapy, and who received 1 or 2 prior systemic therapies for their disease were eligible to enroll on the trial. Additional eligibility criteria included having measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1 prior to randomization, and a life expectancy of at least 3 months.

Those with primary neuroendocrine, lymphoid, or sarcomatoid histology were unable to enroll on the trial. Patients were also unable to enroll on the trial if they had clinically significant bleeding issues, active ocular surface disease, major surgery within 4 weeks of study entry, grade 2 or higher peripheral neuropathy, or any prior treatment with agents containing monomethyl auristatin E.

References

1. Seagen and Genmab announce TIVDAK® (tisotumab vedotin-tftv) improved overall survival in patients with recurrent or metastatic cervical cancer compared with chemotherapy alone. News release. Seagen Inc. and Genmab A/S. September 4, 2023. Accessed September 4, 2023. bit.ly/3r60gnB
2. Seagen and Genmab announce FDA accelerated approval for TIVDAK™ (tisotumab vedotin-tftv) in previously treated recurrent or metastatic cervical cancer. News release. Seagen Inc. and Genmab A/S. September 20, 2021. Accessed September 5, 2023. https://bwnews.pr/2XJLowv