Tisotumab for Advanced Cervical Cancer Awaiting Approval

Roxanne Nelson, RN, BSN

April 20, 2021

Tisotumab vedotin (Seagen/Genlab), an investigational antibody drug conjugate directed against tissue factor, has shown promise for patients with recurrent or metastatic cervical cancer.

When used as monotherapy in previously treated patients, the drug showed "clinically meaningful and durable" antitumor activity. The confirmed objective response rate (ORR) was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The results were published online April 9 in The Lancet Oncology.

"We anticipate it being used as monotherapy in the second-line recurrent/metastatic cervical cancer as well as further lines," said lead investigator Robert Coleman, MD, of US Oncology Research, The Woodlands, Texas.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor (ORR, <15%).

Thus, the new drug would fill an unmet medical need. The data from this phase 2 single-arm trial have led to the US Food and Drug Administration's (FDA's ) granting an accelerated priority review. A decision is expected October 10, 2021.

For an accelerated approval, a confirmatory phase 3 trial must have completed enrollment or have achieved substantial enrollment at the time of the FDA's decision, Coleman explained.

"This is already underway," he said.

The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

This phase 3 trial is "anticipated to support the accelerated approval this year, given the limited options in this population of high unmet need," said Richard T. Penson, MD, a medical oncologist in gynecology at Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

Approached by Medscape Medical News for an independent comment, he said: "This recently published study reported an impressive ORR of 24% with a better toxicity profile than expected with palliative chemotherapy."

The drug is a novel antibody drug conjugate that targets tissue factor, which is expressed on cervical cancer and can promote tumor growth, angiogenesis, and metastasis, he explained. "Although targeting tissue factor might be expected to disrupt coagulation, the trialists only observed a few nose bleeds. The commonest toxicity, conjunctivitis, could be reduced from 80% to 20% with an easy eye care plan."

Details of Clinical Data

Coleman and colleagues conducted a multicenter clinical trial that included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

At data cutoff, the median follow-up was 10.0 months. Four patients remained on treatment. The median duration of treatment was 4.2 months.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months, and the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the authors comment. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The study was funded by Genmab, Seagen, the Gynaecologic Oncology Group, and the European Network of Gynaecological Oncological Trial Groups. Coleman has relationships with several pharmaceutical companies, including Genmab, as do several co-authors. Penson has relationships with several pharmaceutical companies, but not Genlab, as well as with several medical publishers, including WebMD.

Lancet Oncol. Published online April 9, 2021. Abstract

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