UK Researchers Publish Promising Results for New Cancer Treatment in Multiple Tumor Types

A new type of cancer drug has shown promise in patients with 6 different cancer types, according to results of a study published in Lancet Oncology (online ahead of print February 07, 2019; doi:10.1016/S1470-2045(18)30859-3).

Tisotumab vedotin is a first-in-human antibody–drug conjugate directed against tissue factor, which is expressed across multiple solid tumor types and is associated with poor clinical outcomes.

Johann de Bono, MD, PhD, first author on the study and Regius Professor of Cancer Research at The Institute of Cancer Research, London, said in a press release, “What is so exciting about this treatment is that its mechanism of action is completely novel – it acts like a Trojan horse to sneak into cancer cells and kill them from the inside. Our early study shows that it has the potential to treat a large number of different types of cancer, and particularly some of those with very poor survival rates.”

De Bono’s team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust led a phase 1/2, open-label, dose-escalation and dose-expansion study (InnovaTV 201) of tisotumab vedotin with a mixed population of patients with locally advanced or metastatic solid tumors known to express tissue factor who had stopped responding to standard treatments.

Between Dec 9, 2013, and May 18, 2015, 27 eligible patients were enrolled to the dose-escalation phase. In this phase, patients were treated with tisotumab vedotin between 0.3 and 2.2 mg/kg intravenously once every 3 weeks in a traditional 3 + 3 design. However, dose-limiting toxicities were seen at the 2.2 mg/kg dose, so 2.0 mg/kg was established as the recommended phase 2 dose for the dose-expansion phase. A total of 147 eligible patients were enrolled to this phase between Oct 8, 2015, and April 26, 2018. The primary endpoint was the incidence of adverse events and study drug-related adverse events in the full analysis population.

The researchers found that a significant minority of the patients responded to the drug, with their tumors either shrinking or stopping growing. Responses were seen in 27% of patients with bladder cancer, 26.5% with cervical cancer, 14% ovarian cancer, 13% with esophageal, 13% with non-small cell lung cancer, and 7% with endometrial cancer, although not in prostate cancer. Responses lasted an average of 5.7 months and up to 9.5 months in some patients. Across tumor types, the confirmed proportion of patients who achieved an objective response was 15.6% (95% CI 10·2–22·5; 23 of 147 patients).

The most common (in ≥20% of patients) treatment-emergent adverse events of any grade were epistaxis (102 [69%] of 147 patients), fatigue (82 [56%]), nausea (77 [52%]), alopecia (64 [44%]), conjunctivitis (63 [43%]), decreased appetite (53 [36%]), constipation (52 [35%]), diarrhea (44 [30%]), vomiting (42 [29%]), peripheral neuropathy (33 [22%]), dry eye (32 [22%]), and abdominal pain (30 [20%]). The most common adverse events of grade 3 or worse were fatigue (14 [10%] of 147 patients), anemia (8 [5%]), abdominal pain (6 [4%]), hypokalemia (6 [4%]), conjunctivitis (5 [3%]), hyponatremia (5 [3%]), and vomiting (5 [3%]). 67 (46%) of 147 patients had a treatment-emergent serious adverse event. There were 9 deaths across all study phases (3 in the dose-escalation phase and 6 in the dose-expansion phase); only 1 case of pneumonia in the dose-expansion phase was considered possibly related to study treatment.

The study authors concluded that tisotumab vedotin has a manageable safety profile with encouraging preliminary antitumor activity across multiple tumor types in heavily pretreated patients.

Dr de Bono said they have already begun additional trials of this new drug in different tumor types and as a second-line treatment for cervical cancer, where response rates were particularly high. They are also developing a test for expression of a biomarker on the tumor cells to select the patients most likely to respond.

Paul Workman, FMedSci, FRS, chief executive of the Institute of Cancer Research, London, said, “It’s exciting to see the potential shown by [tisotumab vedotin] across a range of hard-to-treat cancers. I look forward to seeing it progress in the clinic and hope it can benefit patients who currently have run out of treatment options.”—Kara Rosania