US clears Seagen, Genmab's Tivdak for cervical cancer

Seagen and Genmab said Monday that the FDA granted an accelerated approval to the antibody-drug conjugate Tivdak (tisotumab vedotin-tftv) as monotherapy to treat adults with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy. The decision, which follows a priority review granted by the FDA in April, was based on tumour response and durability of response data from the Phase II innovaTV 204 trial.

The single-arm study evaluated Tivdak in 101 patients with recurrent or metastatic cervical cancer who had received a maximum of two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen.

Response rate of 24%

Results showed a 24% confirmed objective response rate (ORR) as assessed by an independent review committee, while the median duration of response was 8.3 months. When they unveiled the findings last year, the companies noted that existing therapies for previously treated cervical cancer tend to result in limited ORRs of typically less than 15%, with median overall survival times ranging from 6 months to 9.4 months.

The most common treatment-related adverse events included alopecia, epistaxis, nausea, conjunctivitis, fatigue and dry eye. There was also one death due to septic shock that was considered by the investigator to be related to therapy. The US prescribing information for Tivdak includes a boxed warning about ocular toxicity.

Phase III trial under way

Meanwhile, at this year's European Society for Medical Oncology (ESMO) congress, Seagen and Genmab presented initial results from two cohorts of the Phase Ib/II innovaTV 205 trial. They said the combination of Tivdak plus carboplatin had an ORR of 55% when used as first-line therapy for patients with advanced cervical cancer, while use together with Merck & Co.'s PD-1 inhibitor Keytruda (pembrolizumab) showed an ORR of 38% in previously treated patients. Both combinations demonstrated a "manageable and acceptable safety profile, with no new safety signals," the companies added.

A randomised, open-label Phase III study, dubbed innovaTV 301, started earlier this year to test Tivdak versus investigator's choice chemotherapy in approximately 482 recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy. The primary endpoint is overall survival.

Tivdak, which is given by injection, is composed of Genmab's monoclonal antibody directed to tissue factor (TF) and Seagen's ADC technology that utilises a protease-cleavable linker to attach the cytotoxic agent MMAE to the antibody. Once the ADC-TF complex enters a cancer cell, MMAE is released and disrupts the microtubule network of actively dividing cells, leading to cell death.

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