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One-fourth of patients with previously treated, relapsed, or metastatic cervical cancer responded to an investigational antibody-drug conjugate, according to results of a preliminary trial.

Results in 101 patients showed that 24 patients had objective responses, including seven complete responses. An additional 49 patients had stable disease during treatment with tisotumab vedotin. Almost 80% of patients had some degree of tumor shrinkage.

The therapy was generally well tolerated and associated with a low incidence of grade 3/4 treatment-related adverse events (TRAEs), Robert L. Coleman, MD, of Texas Oncology in the Woodlands, Texas, reported during the 2020 European Society for Medical Oncology (ESMO) virtual congress.

"Tisotumab vedotin demonstrated compelling and durable antitumor activity in recurrent or metastatic cervical cancer previously treated with doublet chemotherapy," Coleman said. "Most responses were rapid, with activity observed within the first two treatment cycles. Clinically meaningful responses were observed regardless of tissue factor expression, histology subtype, or prior therapy.

"Tisotumab vedotin is a potential novel treatment for women with previously treated recurrent or metastatic cervical cancer."

Recurrent and metastatic cervical cancer remains a significant cause of mortality in women. After progression on or development of resistance to first-line standard-of-care chemotherapy, no established second-line therapy exists, Coleman noted. The PD-1 inhibitor pembrolizumab (Keytruda) received accelerated FDA approval on the basis of an (ORR) of 14.3% in PD-L1-positive tumors and a median progression-free survival (PFS) of 2.1 months.

Tisotumab vedotin comprises an antibody directed at tissue factor and covalently linked to the microtubule disruptor MMAE. Tissue factor occurs in a large percentage of cervical cancers and other types of cancer and is associated with poor prognosis, Coleman continued. A of the conjugate led to objective responses in a fourth of patients with previously treated cervical cancer, setting the stage for the multicenter phase II .

Investigators enrolled patients with recurrent or extrapelvic metastatic cervical cancer that had progressed during or after doublet chemotherapy with bevacizumab (if eligible). No more than two prior lines of therapy were allowed. Patients received single-agent tisotumab vedotin continuously until disease progression or development of unacceptable toxicity. The primary endpoint was ORR as determined by independent imaging review.

The 101-patient cohort had a median age of 50, and all but six patients had extrapelvic metastatic disease at baseline. A majority of the patients had received cisplatin-containing chemoradiation, 30% had received two prior lines of therapy, two-thirds had received bevacizumab plus doublet chemotherapy, and more than half had not responded to the most recent systemic regimen.

Coleman reported that 97 patients had discontinued treatment, primarily because of radiographic disease progression (65%), but also because of adverse events (13%) and clinical progression (8%). Four patients died during the trial. Median exposure to the study drug was 4.2 months.

The data showed a disease control rate (response plus stable disease) of 74%, and four patients had yet to be evaluated for response. The median duration of response was 8.3 months. Coleman reported that 79% of patients had some tumor shrinkage as confirmed by independent radiographic review. The median time to response was 1.4 months.

The cohort had a median PFS of 4.2 months, and 30% of patients were alive without disease progression at 6 months. The median overall survival (OS) was 12.1 months, and the 6-month OS rate was 79%.

Coleman said that 76 patients had tissue factor data and were evaluable for response. The distribution of response status (from complete response to progressive disease) had a similar distribution across the range of baseline tissue factor values.

The most common TRAEs were alopecia (38% of patients), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (24%), dry eye (23%), myalgia (15%), anemia (12%), asthenia (12%), arthralgia (12%), decreased appetite (11%), keratitis (11%), and pruritus (10%). Overall, 28% of patients had at least one grade ≥3 TRAE.

The innovaTV 204 trial produced compelling results, including ORR, PFS, and OS, said ESMO-invited discussant Ana Oaknin, MD, PhD, of Vall d'Hebron Institute of Oncology in Barcelona. The TRAEs, though manageable, appeared to occur more often with tisotumab than in trials of PD-1/L1 inhibitors in the same types of patients.

"We are awaiting confirmatory phase III trials, which are mandatory," said Oaknin. "What would be the second-line treatment if PD-1/PD-L1 agents are incorporated in first-line therapy after phase III trial results? Would tisotumab vedotin be the second-line therapy of choice? Would we see the same level of efficacy in a population already treated with immunotherapy? The next steps in the clinical development of tisotumab vedotin are crucial to find its best position in the metastatic and recurrent cervical cancer treatment landscape."

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