BOTHELL, Wash.— Seattle Genetics Inc. announced Sept. 8 that preliminary clinical data for tisotumab vedotin from a Genmab-sponsored phase 1/2 clinical trial (GEN701) were being featured in an oral presentation at the European Society for Medical Oncology (ESMO) Congress held Sept. 8-12, 2017, in Madrid, Spain. Additional data from the trial will also be presented in a poster session.
Tisotumab vedotin is an antibody-drug conjugate (ADC) targeting tissue factor, which is expressed on a broad range of solid tumors. Among patients with cervical cancer treated in the trial, tisotumab vedotin demonstrated an encouraging response rate and manageable safety profile. Tisotumab vedotin is being co-developed by Seattle Genetics and Genmab. The companies are evaluating next steps in the development of tisotumab vedotin for cervical cancer. The GEN701 study is ongoing and further data, including other solid tumor indications, will be published at a later date.
“These encouraging data reinforce our recent decision to exercise our option to co-develop tisotumab vedotin with Genmab, thereby adding another clinical-stage solid tumor ADC program to our pipeline with a potentially rapid registrational pathway,” said Dr. Jonathan Drachman, chief medical officer and executive vice president of research and development at Seattle Genetics. “In the recurrent cervical cancer setting, there is no standard of care and response rates are limited, underscoring the unmet need. Beyond cervical cancer, we believe tisotumab vedotin may have therapeutic potential in other solid tumors, and we are collaborating with Genmab to advance this program to benefit patients.”
Tisotumab vedotin was evaluated in a phase 1/2 two-part trial conducted by Genmab. Part 1 assessed escalating single-agent doses ranging from 0.3 to 2.2 milligrams per kilogram (mg/kg) administered every three weeks in a variety of solid tumors. Part 2 consisted of disease-specific expansion cohorts at the recommended dose of 2.0 mg/kg. Data were reported from an expansion cohort of 34 patients with relapsed, recurrent and/or metastatic cervical cancer with a median age of 43 years. Of these patients, 91 percent had received prior treatment with a platinum and/or taxane-based chemotherapy regimen and 71 percent had received prior bevacizumab (Avastin). Key findings include:
- Of the 34 patients evaluable for response, 11 patients (32 percent) achieved a response. Fifty percent of patients achieved clinical benefit after 12 weeks.
- Median duration of confirmed responses was 8.3 months. Three responders remained on study.
- The most common adverse events of any grade were conjunctivitis (50 percent), epistaxis, fatigue and alopecia (47 percent each) and nausea (44 percent).
- The most common grade 3 or higher adverse events were vomiting (15 percent) and fatigue, nausea and abdominal pain (9 percent each).
- Ocular events of any grade occurred in 53 percent of patients, including three percent with grade 3 or higher. The most common ocular event was conjunctivitis, which was substantially reduced through the introduction of a mitigation plan that involved a prophylactic steroid, lubricating eye drops and cooling eye masks worn during treatment infusion, as well as stricter dose adjustment guidance.
- The part 2 portion of the clinical trial is ongoing in multiple solid tumors, including ovarian, prostate, bladder, esophageal and endometrial.
Cervical cancer originates in the cells lining the cervix, which is the lower part of the uterus. Routine medical examinations and the human papillomavirus (HPV) vaccine have had a positive impact on the incidence of cervical cancer in the developed world. However, even in developed countries, many women do not receive routine medical care or the HPV vaccine, resulting in an unmet medical need particularly for recurrent/metastatic disease. Standard therapies for recurrent/metastatic cervical cancer generally result in response rates of less than 15 percent and a median overall survival of six to eight months.
Tisotumab vedotin is composed of a human antibody that binds to tissue factor (TF) and Seattle Genetics ADC technology that utilizes a cleavable linker and the cytotoxic drug monomethyl auristatin E (MMAE). TF is a protein involved in tumor signaling and angiogenesis. Based on its high expression on many solid tumors and its rapid internalization, TF was selected as a target for an ADC approach. Tisotumab vedotin is in phase 1/2 clinical studies for solid tumors.
