It was always going to be tough for Genmab/Seattle Genetics’ tisotumab vedotin to come close to the 36-46% remission rate seen in a late-line cervical cancer cohort of an earlier trial. So it proved yesterday, with topline data from the Innova-204 study, run specifically in this cancer, showing a more modest response rate of 24%.
The key question now is whether the companies have done enough to get tisotumab, an anti-tissue factor antibody-drug conjugate, before the regulators on these data alone. The bull case has tisotumab being launched for ovarian cancer next year, and representing Genmab’s first self-developed and self-marketed drug.
Jefferies analysts, for one, think the Innova-204 result “should support US filing, for Genmab’s first commercial launch”. In a note to clients this morning they forecast $600m of peak sales for tisotumab, half coming in cervical cancer; sellside consensus compiled by EvaluatePharma sees $369m in 2026.
Though Genmab’s earlier multi-tumour trial, GEN701, had shown tisotumab to put 46% and 36% of third and second-line cervical cancer subjects respectively into remission, the benchmark set for Innova-204 was 20%.
Like most oncology studies in salvage settings Innov-204 did not have a control cohort. But one trial found that chemotherapy in third-line cervical cancer gave an ORR of just 10%, while Merck & Co’s Keytruda was approved in second-line, PD-L1-positive disease on the strength of a 14% ORR in the Keynote-158 study.
Teasing out the benefit
When the Innova-204 trial is presented in full – this year’s Esmo meeting is a possible venue – analysts will no doubt want to dig into baseline demographics. Patients had to have received no more than two prior systemic treatments, so the precise benefit in third-line subjects, the likeliest setting for an initial approval, will have to be teased out.
Another consideration will be whether tisotumab’s toxicities do not overshadow the quality of whatever extra life the project might bring. In Innova-204 at least 20% of patients suffered alopecia, nose bleeds, nausea, conjunctivitis, fatigue and dry eye, the companies have disclosed.
A separate cervical cancer study, Innova-205, tests tisotumab in combination with Avastin, Keytruda or chemotherapy, and should read out some time next year. This will include some front-line subjects.
The collaboration between Genmab and Seattle dates back 10 years, and in 2011 the latter company acquired rights to opt into tisotumab after phase I. This option, giving Seattle co-development and co-promotion rights, was exercised in 2017, after the GEN701 data came out.
Through recently approved drugs like Tukysa and Padcev Seattle is slowly reducing its dependence on Adcetris. Tisotumab is important for it and Genmab alike.