"Transformational" innovaTV Long-Term OS Data for Cervical Cancer

Bradley Monk, MD, discusses the long-term follow-up of the innovaTV trial, with data presented at the European Society for Medical Oncology (ESMO) 2025 meeting.

Monk begins by reviewing the evolution of preferred chemotherapy backbones for first-line cervical cancer.

• 2009: The initial preferred chemotherapy backbone of platinum and taxane was published in the Journal of Clinical Oncology.
• 2014: The first targeted therapy ever approved in a gynecologic cancer, bevacizumab (Avastin), was added to the backbone. This "earth-shattering" combination was published in The New England Journal of Medicine.
• More Recently: For the third time, the combination was enhanced with the addition of pembrolizumab (Keytruda) in the first line. Patients could now receive 4 medications—platinum, taxane, bevacizumab, and pembrolizumab—with a small potential for cure even in the metastatic setting. This was also published in The New England Journal of Medicine.

With chemotherapy, antiangiogenic therapy, and immunotherapy already in use, the next logical step was to investigate an antibody-drug conjugate (ADC).

In the second-line setting, the preferred treatment was established as tisotumab vedotin (Tivdak), an ADC against tissue factor, which is agnostic of the biomarker. This was established through a Gynecologic Oncology Group (GOG) study, with the phase 3 results ultimately published in The New England Journal of Medicine.

Monk, as the GOG principal investigator, then discussed the next step: exploring combinations of these agents—chemotherapy, bevacizumab, pembrolizumab, and tisotumab vedotin—to test for both safety and ultimately, efficacy.

The innovaTV trial investigated 3 key arms:

1. Tisotumab vedotin + carboplatin (TV-carbo): This arm replaced paclitaxel in the front line.
2. Tisotumab vedotin + pembrolizumab (TV-pembro) in the first line.
3. Tisotumab vedotin + pembrolizumab (TV-pembro) in the second line.

The primary focus of the poster presented at ESMO 2025 was to report the long-term outcomes, specifically long-term progression-free survival and overall survival.

Monk describes the results as "transformational."

• First-line TV-carbo: The confirmed objective response rate was 54.5%. This is very similar to the response rate for carboplatin/paclitaxel. The rationale for replacing paclitaxel with tisotumab vedotin is to avoid the former's adverse effects, such as alopecia, bone marrow suppression, and fatigue. While the performance was similar, Monk notes this combination is provocative.
• First-line TV-pembro: This regimen had an objective response rate of 40.6%.
• Second-line TV-pembro: his is considered the most important finding because most patients do not receive pembrolizumab in the front line. When they reach the second line, they have 2 FDA-approved options: tisotumab vedotin or pembrolizumab. The data confirms they can receive both agents for a combined overall response rate of 35.3%.

This second-line combination is so significant that it is now NCCN recommended. The long-term data showed a median overall survival (OS) of 15.3 months for the second-line tisotumab vedotin and pembrolizumab arm. Monk emphasizes the transformative nature of this finding, offering a "small chance of cure" and a substantial increase in OS for women who have been intensely pretreated with chemotherapy, radiation, carboplatin, paclitaxel, and likely bevacizumab.