By Reuters Staff
NEW YORK (Reuters Health) - 19/2/2019
A new cancer drug has shown promise against multiple tumor types, in a first-in-human trial.
Tisotumab vedotin appeared to be manageably safe and provided an objective response in some patients with advanced or metastatic solid tumors, researchers say.
Tisotumab vedotin is a fully human monoclonal antibody specific for tissue factor conjugated to the microtubule-disrupting agent monomethyl auristatin E. The antibody induces potent cytotoxicity in tissue factor-positive tumor cells in vitro and in murine xenograft tumor models in vivo.
With funding from Genmab A/S, Dr. Johann S. de Bono from Royal Marsden NHS Foundation Trust, in London, and colleagues from five countries investigated the safety, tolerability and antitumor activity of tisotumab vedotin in a phase 1-2 open-label study (InnovaTV 201) of 174 patients with locally advanced or metastatic (or both) solid tumors known to express tissue factor.
In the dose-escalation phase, three of 27 patients experienced dose-limiting toxicity; the maximum tolerated dose (and recommended phase 2 dose) was defined as 2.0 mg/kg.
During a median 2.8 months of follow-up in the dose-expansion phase, 27 (18%) of 147 patients treated required one or more dose reductions. Treatment-emergent adverse events of grade 3 or worse occurred in 93 patients (63%).
Epistaxis was the most commonly reported bleeding-related adverse event (69%), and neuropathy of any grade occurred in 43%, with 7% having neuropathy of at least grade 3.
There were three deaths in the dose-escalation phase, but none was judged related to study drug, the researchers report in The Lancet Oncology, online February 7.
In the dose-escalation phase, one patient with metastatic cervical cancer achieved a partial response at the 1.2 mg/kg dose. In the dose-expansion phase, 23 patients (15.6%) achieved a confirmed objective response (all of them partial).
The median confirmed duration of response was 5.7 months, and the median progression-free survival of responders was 3.0 months.
"Our findings support further investigation of tisotumab vedotin," the researchers note. "Several studies are underway, including InnovaTV 207 and InnovaTV 204. InnovaTV 207 (NCT03485209) is an ongoing phase 2 study evaluating the activity, safety, and tolerability of tisotumab vedotin monotherapy administered every 3 weeks in patients with relapsed, locally advanced or metastatic colorectal cancer, squamous non-small-cell lung cancer, pancreatic cancer, or squamous cell carcinoma of the head and neck."
"Following on from the encouraging preliminary activity seen in the cervical cancer cohort in this study," they say, "InnovaTV 204 (NCT03438396) is an ongoing phase 2 study evaluating the activity, safety, and tolerability of tisotumab vedotin monotherapy in patients with recurrent or metastatic cervical cancer that had progressed during or after treatment with standard first-line therapy."
Genmab employed several of the authors and paid for manuscript preparation. Dr. de Bono, who reported financial to the company, did not respond to a request for comments.
Lancet Oncol 2019.