Phase 3 Trial Results Show Tisotumab-Vedotin Improved OS in Adult Patients With Recurrent or Metastatic Cervical Cancer


In addition to overall survival, main efficacy outcomes, such as progression-free survival, objective response rate, and time to response, were compared to chemotherapy alone.

The phase 3 innovaTV 301 global trial (NCT04697628) met its primary endpoint of overall survival (OS), according to study investigators. Recurrent or metastatic cervical cancer patients with disease progression who received tisotumab-vedotin-tftv (Tivdak; Seagan) treatment on or after front-line therapy, compared with chemotherapy alone, had an improved OS during a time frame of up to approximately 2 years.1,2

Patient consulting with her gynecologist

Image credit: rh2010 |

The innovaTV 301 trial is a global, randomized, open-label trial evaluating treatment with tisotumab-vedotin compared to chemotherapy alone (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who had received no more than 2 prior systemic treatments in the recurrent or metastatic setting. Participants will be divided into 2 groups, 1 of which will be treated with tisotumab-vedotin. In the study, patients enrolled had recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology. Further, main efficacy outcomes included OS, progression-free survival, objective response rate, time to response and duration of response, and safety and quality of life outcomes.1,2

Tisotumab-vedotin is an antibody-drug conjugate (ADC) made up of monoclonal antibody directed to tissue factor (TF) and ADC technology that uses a protease-cleavable linker which covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Prior nonclinical data suggest that the anticancer activity of tisotumab-vedotin is due to the binding of the ADC to TF-expressing cancer cells, the internalization of the ADC-TF complex, and release of MMAE through proteolytic cleavage. Further, MMAE disturbs the microtubule network of actively dividing cells, resulting in cell cycle arrest and the death of apoptotic cells. In addition, tisotumab-vedotin mediates antibody-dependent cellular phagocytosis as well as antibody-dependent cellular cytotoxicity in vitro.1

Tisotumab-vedotin was granted accelerated approval by the FDA in September 2021 to treat adult patients with recurrent or metastatic cervical cancer with disease progression during or after receiving chemotherapy, making tisotumab-vedotin the first and only ADC to receive approval for this particular treatment. Further, the indication is approved under accelerated approval depending on the tumor response rate and the durability of response, with continued approval depending on the verification of its benefits in clinical trials.1

“[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,” said Roger Dansey, MD, president of research and development and chief medical officer of 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.”1

Potential adverse effects (AEs) when using tisotumab-vedotin include ocular reactions (eg, conjunctival AEs, dry eye, corneal AEs, and blepharitis), peripheral neuropathy (PN; eg, peripheral sensory neuropathy, peripheral sensorimotor neuropathy, motor neuropathy, muscular weakness, and demyelinating peripheral polyneuropathy), hemorrhage (eg, epistaxis, hematuria, vaginal hemorrhage), pneumonitis, severe cutaneous AEs, and embryo-fetal toxicity. The most common AEs, including laboratory malfunctions, consisted of hemoglobin decrease, fatigue, lymphocyte reductions, nausea, PN, alopecia, epistaxis, conjunctival AEs, hemorrhage, leukocytes decreased, creatinine, increased, dry eye, diarrhea, and rash.1

Serious AEs were present in 43% of patients, with the most common being ileus, hemorrhage, pneumonia, PN, sepsis, constipation, and pyrexia. Fatal AEs occurred in 4% of patients who received tisotumab-veotin, and included septic shock, pneumonitis, sudden death, and multisystem organ failure (each at 1% of patients).1

“With limited options for [patients advanced cervical cancer] 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 of Genmab, in the press release. “These results provide hope for patients with recurrent or metastatic cervical cancer.”1


1. Genmab. 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. September 4, 2023. Accessed September 5, 2023.

2. Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer (innovaTV 301). identifier: NCT04697628. Updated August 29, 2023. Accessed September 5, 2023.

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