Tisotumab Vedotin Achieves a Statistically Significant OS Improvement in Advanced Cervical Cancer

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Tisotumab vedotin (Tivdak) administered as treatment for patients with recurrent or metastatic cervical cancer achieved a significant improvement in overall survival (OS) compared with chemotherapy, meeting the primary end point of the phase 3 innovaTV 301 clinical trial (NCT04697628).¹

The OS result was determined by an Independent Data Monitoring Committee (IDMC). At the interim analysis, the IDMC found that the pre-specified threshold for OS improvement was crossed. Statistically significant improvement was also shown in the secondary end points of progression-free survival and objective response rate (ORR). Safety wise, the profile for tisotumab vedotin in the innovaTV301 study was consistent with the known profile.

“[Tisotumab vedotin] is the only United States Food and Drug Administration-approved therapy in second-line recurrent or metastatic cervical cancer regardless of biomarker status, tumor histology and prior therapy,” said Roger Dansey, MD, President of Research and Development and chief medical officer at Seagen, in a press release. “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.”

The accelerated approval for tisotumab vedotin as treatment of recurrent or metastatic cervical cancer was granted based on the phase 2 innovaTV 204 study (NCT03438396). In the study, treatment with tisotumab vedotin led to an ORR of 24% (95% CI, 15.9%-33.3%) with complete responses in 7% of patients, partial responses in 17%, stable disease in 49%, and progressive disease in 24%. In addition, there was a 79% decrease in target lesion size from baseline observed in the study. Most patients treated with tisotumab vedotin in the innovaTV204 had quickly occurring and durable responses. The time to response was 1.4 months (range, 1.1-5.1), with responses lasting for a median of 8.3 months (range, 4.2–not reached).

Continued approval of tisotumab vedotin for recurrent or metastatic cervical cancer is contingent upon confirmatory data in the phase 3, randomized clinical trial.

In innovaTV 301, a total of 506 patients with recurrent or metastatic cervical cancer will be evaluated. Patients in the experimental arm received 2.0 mg/kg every of tisotumab vedotin, every 3 weeks. In the control arm, patients received chemotherapy of investigator’s choice, which may be one of the following.

• Topotecan 1 or 1.25 mg/m² intravenous (IV) on days 1 to 5, every 21 days.
• Vinorelbine 30 mg/m² IV on days 1 and 8, every 21 days.
• Gemcitabine 1000 mg/m² IV on days 1 and 8, every 21 days.
• Irinotecan 100 or 125 mg/m² IV weekly for 28 days, every 42 days.
• Pemetrexed 500 mg/m² IV on day 1, every 21 days.

Other end points to be explored in innovaTV 301 include time to response, duration of response, incidence of adverse events, and health-related quality of life measures.

Patients eligible for inclusion in the confirmatory study are those with recurrent or metastatic cervical cancer whose disease progressed on standard-of-care chemotherapy who have received 1 or 2 prior systemic therapy regimens for their disease, have measurable disease, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months.

“With limited options for advanced cervical cancer patients who have progressed after front-line therapy, there is a need for therapeutic options with new mechanisms of action, particularly those with a demonstrated survival benefit,” said Jan van de Winkel, PhD, chief executive officer, Genmab, in the press release. “These results provide hope for patients with recurrent or metastatic cervical cancer.”

_REFERENCES:

_{1. Genmab and Seagen announce that Tivdak® (tisotumab vedotin-tftv) met its primary endpoint of improved overall survival in patients with recurrent or metastatic cervical cancer compared to chemotherapy. News release. Genmab A/S and Seagen, Inc. September 4, 2023. Accessed September 5, 2023. http://tinyurl.com/35h93ry7}

_{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. September 20, 2021. Accessed September 5, 2023. https://bit.ly/3AE9bgC}

_{3. Tisotumab vedotin vs chemotherapy in recurrent or metastatic cervical cancer (innovaTV 301). ClinicalTrials.gov. Updated August 29, 2023. Accessed September 5, 2023. http://tinyurl.com/3fzup7r5}