Genmab and Pfizer's Biologics License Application (sBLA) for the use of Tivdak (tisotumab vedotin) as a treatment for patients with recurrent or metastatic cervical cancer has been approved US Food and Drug Administration (FDA).
This FDA action converts the September 2021 accelerated approval of Tivdak to a full approval. Tivdak is the first antibody-drug conjugate (ADC) with demonstrated overall survival data to be granted full FDA approval in this patient population.
The study
The approval is based on results from the global, randomised, Phase III innovaTV 301 clinical trial (NCT04597628), in which Tivdak met its primary endpoint of overall survival (OS) in patients with previously treated recurrent or metastatic cervical cancer compared to chemotherapy. Secondary endpoints of progression-free survival (PFS) and a confirmed objective response rate (ORR) were also met.
In October 2023, results from the innovaTV 301 study were initially disclosed during the Presidential Symposium at the European Society of Medical Oncology (ESMO) Congress.
“As a treating physician, it is encouraging to see overall survival data among these patients and a manageable safety profile with tisotumab vedotin,” said Brian Slomovitz, Director of Gynecologic Oncology and Co-Chair of the Cancer Research Committee at Mount Sinai Medical Center, Miami Beach. “Treatment options for patients with advanced or recurrent cervical cancer are limited. The five-year survival rate for patients who have metastatic disease at diagnosis is less than 20% in the U.S. There is a high unmet need for more treatment options that have demonstrated survival benefit in the contemporary treatment landscape. The approval of tisotumab vedotin brings us a step closer to fulfilling that need.”
The results
The innovaTV 301 study met its primary endpoint of OS, demonstrating a 30% reduction in the risk of death compared with chemotherapy (Hazard ratio [HR]: 0.70 [95% CI: 0.54, 0.89], two-sided p=0.0038ii). Median OS for patients treated with TIVDAK was 11.5 months [95% CI: 9.8-14.9] versus chemotherapy 9.5 months [95% CI: 7.9-10.7].
The safety profile of TIVDAK in innovaTV 301 was consistent with its known safety profile as presented in the US prescribing information which includes a boxed warning for ocular toxicity, with no new issues identified.
Side effects
The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving Tivdak were:
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a decrease in haemoglobin (41%)
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peripheral neuropathy (38%)
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conjunctival adverse reactions (37%)
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an increase of aspartate aminotransferase (34%)
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nausea (33%)
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an increase of alanine aminotransferase (30%)
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fatigue (28%)
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a reduction in sodium (27%)
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epistaxis (26%)
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constipation (25%)
The sBLA application received a Priority Review Designation, which is granted by the FDA to medicines that may offer significant advances in treatment or provde a solution to a disease where no adequate therapies exist.
Tivdak was granted accelerated approval in the US by the FDA in September 2021, based on tumour response and durability of response from the innovaTV 204 pivotal Phase II single-arm clinical trial evaluating TIVDAK as a monotherapy in patients with previously treated recurrent or metastatic cervical cancer.