In a phase Ib/II study (innovaTV 205/GOG-3024/ENGOT-cx8) reported in the Journal of Clinical Oncology, Ignace B. Vergote, MD, PhD, and colleagues found that tisotumab vedotin-tftv combined with carboplatin or pembrolizumab showed activity in both treatment-naive and previously treated patients with recurrent or metastatic cervical cancer.
Ignace B. Vergote, MD, PhD
Study Details
In the open-label multicenter study, 41 patients in a dose-escalation phase and 101 in a dose-expansion phase were enrolled between February 2019 and December 2020. The dose-escalation phase assessed dose-limiting toxicities and identified the recommended phase II dose for tisotumab vedotin in combination with bevacizumab, pembrolizumab, or carboplatin. The dose-expansion phase assessed activity of tisotumab vedotin in combination with carboplatin as first-line treatment and with pembrolizumab as first-line or second-/third-line treatment at the recommended phase II doses. The primary endpoint of the dose-expansion phase was objective response rate.
Key Findings
In the dose-escalation phase, no dose-limiting toxicities were identified; the recommended phase II doses were tisotumab vedotin at 2 mg/kg plus bevacizumab at 15 mg/kg on day 1, pembrolizumab at 200 mg on day 1, and carboplatin at area under the curve = 5 on day 1, all once every 3 weeks.
In the dose-expansion phase, objective responses at the recommended phase II doses were observed in:
- 18 (54.5%, 95% confidence interval [CI] = 36.4%–71.9%) of 33 patients receiving first-line tisotumab vedotin plus carboplatin
- 13 (40.6%, 95% CI = 23.7%–59.4%) of 32 patients receiving first-line tisotumab vedotin plus pembrolizumab
- 12 (35.3%, 95% CI = 19.7%–53.5%) of 34 patients receiving second-/third-line tisotumab vedotin plus pembrolizumab.
Median response durations were 8.6 months (95% CI = 4.2–11.5 months), not reached (95% CI = not reached to not reached), and 14.1 months (95% CI = 4.2 months to not reached), respectively.
Grade ≥3 adverse events that occurred in ≥ 15% of patients were anemia, diarrhea, nausea, and thrombocytopenia with first-line tisotumab vedotin plus carboplatin; none with first-line tisotumab vedotin plus pembrolizumab; and anemia with second-/third-line tisotumab vedotin plus pembrolizumab.
The investigators concluded, “Tisotumab vedotin in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated relapsed or metastatic cervical cancer.”
Dr. Vergote, of Belgium and Luxembourg Gynaecological Oncology Group, Leuven Cancer Institute, Belgium, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Genmab A/S and Seagen Inc. For full disclosures of the study authors, visit ascopubs.org.
