The companies are moving closer to traditional approval for the antibody-drug conjugate Tivdak, which met its primary endpoint for overall survival in an interim analysis.
Pictured: Illustration of antibody-drug conjugates with cytotoxic payloads/iStock, Love Employee
Interim data from the Phase III innovaTV 301 trial showed that Genmab and Seagen’s antibody-drug conjugate Tivdak (tisotumab vedotin-tftv) met its primary endpoint, leading to significant survival benefit in patients with metastatic cervical cancer, the companies announced Monday.
While Genmab and Seagen did not provide specific data in their announcement, they said that an Independent Data Monitoring Committee found the study’s overall survival (OS) data “crossed the pre-specified efficacy boundary at interim analysis.”
Key secondary metrics, including objective response rate and investigator-assessed progression-free survival, also met statistical significance.
Patients with advanced cervical cancer who progress after front-line therapy have few treatment options, particularly those with new mechanisms of action and with a demonstrated survival benefit, Genmab CEO Jan van de Winkel said in a statement. “These results provide hope for patients with recurrent or metastatic cervical cancer.”
InnovaTV 301 is a randomized and open-label study enrolling more than 500 patients who had received no more than two previous lines of systemic therapies in the recurrent or metastatic setting. Participants were treated with either Tivdak or an investigator’s choice of chemotherapy, such as irinotecan, topotecan or gemcitabine.
Aside from efficacy, innovaTV 301 also assessed Tivdak’s safety in this setting and found that its adverse event profile was consistent with what had been previously established. The Phase III trial found no new safety signals.
Genmab and Seagen will present the complete analysis of innovaTV 301 at an upcoming medical conference.
Tivdak is a first-in-class antibody-drug conjugate that works by targeting Tissue Factor, a protein commonly found on the surface of cervical cancer cells, and delivering a potent microtubule-disrupting agent monomethyl auristatin E directly to its target tumor cell. Tivdak won the FDA’s accelerated approval in September 2021 for the treatment of recurrent or metastatic cervical cancer after chemotherapy.
The treatment carries a boxed warning for ocular toxicities. Treated patients may see changes in the corneal epithelium and conjunctiva, which in turn may lead to vision loss and corneal ulceration. Ophthalmic exams should be conducted at baseline before each dose and whenever clinically indicated.
In June 2022, the pharma partners reported Phase Ib/II data from the innovaTV 205 trial showing that Tivdak, either as a monotherapy or in combination with other therapies, led to a confirmed objective response rate of 41%.
Seagen and Genmab conducted the Phase III innovaTV 301 to serve as Tivdak’s confirmatory trial, providing the basis for its conversion to traditional approval. The partners will also use data from the pivotal confirmatory trial for regulatory applications abroad.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
