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Tivdak Shows Significantly Greater Efficacy vs. Chemotherapy in Second-, Third-Line Treatment of Recurrent Cervical Cancer

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Data from the Phase III innovaTV 301/ENGOT-cx12/GOG-3057 trial (NCT04697628) show second- or third-line treatment with Tivdak (tisotumab vedotin-tftv) achieved superior efficacy compared with chemotherapy treating patients with recurrent cervical cancer.1,2 Tivdak previously demonstrated promising and durable responses in the second- and third-line treatment of recurrent cervical cancer the Phase II innovaTV 204/ENGOT-cx6/GOG-3023 trial, prompting the FDA to grant the drug accelerated approval in September 2021 for patients with recurrent or metastatic cervical cancer with disease progression on or following chemotherapy. The accelerated approval was converted to a full approval in April 2024.3

“In a previous trial involving [Tivdak] (innovaTV 204), the subgroup of patients who had not received previous bevacizumab therapy had a higher objective response rate than patients who had received previous bevacizumab therapy,” the study authors wrote. “Given the evolving role of immunotherapy in earlier lines of treatment, our trial showed the benefit of [Tivdak] over chemotherapy in patients with recurrent cervical cancer regardless of previous receipt of an anti–PD-1 or anti–PD-L1 agent.”1

Tivdak is an antibody drug conjugate (ADC) that targets tissue factor (TF) on tumor cells. The drug comprises a TF-directed antibody attached to a cytotoxic microtubule inhibitor, monomethyl auristatin E. ADCs are targeted therapies that have demonstrated promising results treating certain cancer types, such as acute leukemia, breast cancer, and Hodgkin lymphoma. An ADC is comprised of a cytotoxic drug artificially combined with a monoclonal antibody that has been developed to transport, selectively target, and bind to tumor antigens. The treatment delivers its cytotoxic payload to the tumor sites, subsequently resulting in cell death.4

Cervical cancer has a five-year relative survival rate of 66.3% and a 17.6% five-year survival rate in patients with distant metastatic disease. Further, up to 15% of adults diagnosed with cervical cancer have metastatic disease, and among those diagnosed at earlier stages and who were administered treatment, up to 31.5% experience disease recurrence.5

The multinational, open-label innovaTV 301/ENGOT-cx12/GOG-3057 trial randomly assigned 253 patients to receive Tivdak monotherapy at a dose of 2.0 mg per kilogram of body weight every three weeks and 249 patients to receive investigator’s choice of chemotherapy with topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The trial’s primary endpoint of overall survival was significantly longer among patients administered Tivdak compared to patients in the chemotherapy cohort at 11.5 months (95% confidence interval [CI], 9.8 to 14.9) vs. 9.5 months (95% CI, 7.9 to 10.7). This translates to a 30% lower risk of death in the Tivdak cohort compared with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P=0.004).

Median progression-free survival in the Tivdak cohort was 4.2 months (95% CI, 4.0 to 4.4) compared to 2.9 months (95% CI, 2.6 to 3.1) in the chemotherapy cohort (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate in the Tivdak cohort was 17.8% compared to 5.2% in the chemotherapy cohort (odds ratio, 4.0; 95% CI, 2.1 to 7.6; two-sided P<0.001).

In terms of safety, 98.4% of patients in the Tivdak cohort had at least one adverse event (AE) during the treatment period compared with 99.2% of patients in the chemotherapy cohort. Grade 3 or greater AEs were reported by 52.0% of patients in the Tivdak cohort compared with 62.3% of patients in the chemotherapy cohort, with 14.8% of patients in the Tivdak cohort discontinuing treatment due to toxic effects.

“The innovaTV 301 trial showed that [Tivdak] resulted in significantly greater efficacy, including longer overall survival, than chemotherapy in patients with recurrent cervical cancer,” the study authors concluded. “Taken together, these data suggest that [Tivdak] may be a preferred second-line or third-line treatment option over chemotherapy for patients with recurrent cervical cancer.”1

References

1. Vergote I, 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. Vol. 391 No. 1. Published July 3, 2024.

2. Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer (innovaTV 301). ClinicalTrials.gov. June 18, 2024. Accessed July 10, 2024. https://clinicaltrials.gov/study/NCT04697628

3. FDA Grants Full Approval for Tivdak to Treat Recurrent or Metastatic Cervical Cancer. News release. Pfizer. April 29, 2024. Accessed July 10, 2024. https://www.pfizer.com/news/press-release/press-release-detail/fda-grants-full-approval-tivdakr-treat-recurrent-or

4. Chau CH, Steeg PS, Figg WD. Antibody-drug conjugates for cancer. Lancet. 2019;394(10200)793-804. doi:10.1016/S0140-6736(19)31774-X. Accessed July 10, 2024.

5. TIVDAK® Supplemental Biologics License Application Accepted for Priority Review by FDA for Patients with Recurrent or Metastatic Cervical Cancer. Pfizer. News release. January 9, 2024. Accessed July 10, 2024. https://www.pfizer.com/news/press-release/press-release-detail/tivdakr-supplemental-biologics-license-application-accepted