In the global randomized open-label phase III innovaTV 301/ENGOT-cx12/GOG-3057 trial, treatment with the antibody-drug conjugate tisotumab vedotin-tftv resulted in a statistically significant 30% reduction in the risk of death in patients previously treated for recurrent or metastatic cervical cancer, as compared with investigator’s choice of single-agent chemotherapy.1
“Tisotumab vedotin showed a statistically significant and clinically meaningful improvement in overall survival. Consistent benefits in progression-free survival and confirmed objective response rates were also observed and supportive of the overall survival benefit. Based on these data, tisotumab vedotin should be considered as a potential new standard of care for patients who have experienced disease progression after first-line systemic therapy,” said lead investigator Ignace B.Vergote, MD, PhD, Professor at the Catholic University of Leuven in Belgium and cofounder of the European Network of Gynaecological Oncological Trial groups (ENGOT).
Ignace B.Vergote, MD, PhD
The results, including overall and progression-free survival benefits, were presented during the Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2023 by Dr. Vergote.1
Tisotumab vedotin is an investigational antibody-drug conjugate composed of a tissue factor–directed human monoclonal antibody covalently linked to the microtubule-disrupting agent monomethyl auristatin E. It received accelerated approval from the U.S. Food and Drug Administration for treatment of patients with recurrent or metastatic cervical cancer that progressed on or after chemotherapy, based on the phase II innovaTV 204/GOG-3023/ENGOT-cx6 study.2 The innovaTV 301 trial is intended to serve as the pivotal confirmatory trial for U.S. and European Union approval and to support potential global regulatory applications.
About innovaTV 301/ENGOTcx12/GOG-3057
The innovaTV 301 trial evaluated tisotumab vedotin vs investigator’s choice of single-agent chemotherapy in 502 patients with recurrent or metastatic cervical cancer who had received one or two prior regimens in the recurrent setting. Patients received tisotumab vedotin at 2.0 mg/kg every 3 weeks or investigator’s choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The treatment arms were balanced, with three-quarters being from Europe or Asia, almost two-thirds having squamous cell carcinoma, 90% having extrapelvic metastases, and about 60% receiving one prior regimen.
Multiple Endpoints Met
After a median follow-up of 10.8 months, median overall survival, the primary endpoint, was 11.5 months with tisotumab vedotin and 9.5 months with chemotherapy (hazard ratio [HR] = 0.70; P = .0038), resulting in a 12-month overall survival rate of 48.7% vs 35.3%, respectively, Dr. Vergote reported. “The P value of .0038 was far below what we needed for statistical significance,” he noted.
Median progression-free survival was 4.2 months vs 2.9 months, respectively, a 33% reduction in risk (HR = 0.67; P < .0001), with 30.4% vs 18.9%, respectively, progression-free at 6 months. Overall survival and progression-free survival were generally consistent across key subgroups, including those who received prior immunotherapy in addition to prior chemotherapy, Dr. Vergote said.
The confirmed objective response rate was also significantly improved with tisotumab vedotin (17.8% vs 5.2%; P < .0001), with all six complete responses (2.4%) seen in the experimental arm. The disease control rate was 75.9% vs 58.2%, respectively, and the median duration of response was about 5 months in each arm.
Treatment-related adverse events occurring in patients with tisotumab vedotin were generally of low grade and manageable, according to the investigators. The proportion of patients with grade ≥ 3 toxicities was actually lower with tisotumab vedotin than with chemotherapy (29.2% vs 45.2%). The most common grade ≥ 3 adverse events of special interest with tisotumab vedotin were peripheral neuropathy (5.2%), ocular toxicities (3.2%), and bleeding (0.8%). Treatment-related deaths occurred in two patients receiving tisotumab vedotin (acute kidney injury and Stevens-Johnson syndrome) and one receiving chemotherapy (pancytopenia). “There were no grade 4 or 5 adverse events of special interest with tisotumab vedotin,” he said.
DISCLOSURE: Dr. Vergote reported financial relationships with Agenus, Aksebio China, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, F. Hoffmann–LaRoche, Genmab, GSK, Immunogen, Jazz Pharma, Karyopharm, MSD, Novocure, Novartis, Oncoinvent AS, Seagen, Sotio a.s., Elevar Therapeutics, Mersana, Verastem Oncology, Zentalis, Amgen Europe, Clovis Oncology, Carrick Therapeutics, Millennium Pharmaceuticals, Amgen, and Roche.
REFERENCES
1. Vergote IB, Gonzalez MA, 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. ESMO Congress 2023. Abstract LBA9. Presented October 22, 2023.
2. Coleman RL, Lorusso D, Gennigens C, et al: Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): A multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 22:609-619, 2021.
