Based on strong overall and progression-free survival data in its Phase III confirmatory study, Pfizer and Genmab’s antibody-drug conjugate Tivdak on Monday secured the FDA’s full approval for recurrent or metastatic cervical cancer that had progressed on or after chemotherapy.
Pictued: Pfizer sign at its world headquarters in New York/iStock, JHVEPhoto
The FDA on Monday granted full approval to Pfizer and Genmab’s antibody-drug conjugate Tivdak (tisotumab vedotin-tftv) for the treatment of recurrent or metastatic cervical cancer that had progressed on or after chemotherapy.
Chris Boshoff, chief oncology officer at Pfizer, said in a statement that Monday’s regulatory victory “reinforces the important role of Tivdak” for the treatment of patients with this condition, which he calls “a particularly devastating and mostly incurable disease.”
“Patients are in need of survival-extending treatment options,” Boshoff continued, noting that Tivdak is “the first antibody-drug conjugate with statistically significant prolonged overall survival data.”
Originally developed under a partnership between Seagen and Genmab, Tivdak is an antibody-drug conjugate (ADC) that targets the cell surface tissue factor protein, which is an important part of the blood coagulation cascade. Its toxic payload is monomethyl auristatin E, a microtubule-disrupting agent that triggers cell death.
Pfizer took over Seagen’s half of the deal when it bought the cancer-focused biotech in March 2023 for $43 billion.
Based on a 24% objective response rate from the Phase II innovaTV 204 trial, the FDA granted Tivdak its accelerated approval in September 2021. The mid-stage study also showed a median duration of response of 8.3 months.
As part of their obligations under the FDA’s accelerated pathway—and to keep Tivdak on the market—Pfizer and Genmab ran the Phase III innovaTV 301 study, which ultimately became the basis for Monday’s full approval.
The late-stage confirmatory trial, a randomized and open-label study that enrolled more than 500 patients who had undergone at most two prior rounds of systemic treatment, showed that the ADC could significantly boost survival versus chemotherapy.
A readout in October 2023 demonstrated that Tivdak cut the risk of death by 30% in patients with recurrent or metastatic cervical cancer, an effect that the companies at the time called “statistically significant and clinically meaningful.” The ADC also led to a significant improvement in progression-free survival, reducing the risk of death or worsening disease by 33% versus chemotherapy.
Tivdak also aced its key secondary endpoints, including objective response rate and disease control rate. In terms of safety, innovaTV 301 found Tivdak’s adverse events to be consistent with what had been established in prior studies. No new signals of concern were documented.
However, Tivdak comes with a boxed warning for ocular toxicity, notifying prescribers of its risk of inducing changes in the corneal epithelium and conjunctiva, which has the potential to lead to loss of vision. Patients should undergo ophthalmic evaluation at baseline and before each dose, according to the label.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
