Preliminary clinical data for tisotumab vedotin, also known as HuMax®-TF-ADC from a Genmab-sponsored phase I/II clinical trial (GEN 701) were featured today in an oral presentation at the ESMO 2017 Congress held September 8 – 12, 2017 in Madrid, Spain, organized by the European Society for Medical Oncology (ESMO).  A separate poster of the trial includes additional trial results.
Tisotumab vedotin is an antibody-drug conjugate (ADC) which includes a monoclonal antibody targeting tissue factor (TF), a protein involved in tumor signaling and angiogenesis expressed on a broad range of solid tumors. The ADC contains a cleavable linker and the cytotoxic drug monomethyl auristatin E or MMAE.
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 I/II clinical studies for solid tumors, including cervical cancer.
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% and a median overall survival of 6 to 8 months.
Among patients with cervical cancer treated in the trial, tisotumab vedotin demonstrated an encouraging response rate and manageable safety profile.
Earlier this year Seattle Genetics exercised its option to co-develop tisotumab vedotin with Genmab. The companies originally entered into a commercial license and collaboration agreement in October 2011 under which Seattle Genetics had the right to exercise a co-development option for tisotumab vedotin at the end of Phase I clinical development. As part of this process, the companies are evaluating next steps in the development of tisotumab vedotin for cervical cancer.
“Our ADC partnership with Genmab has generated promising Phase I/II data for tisotumab vedotin in patients with recurrent cervical cancer. As Seattle Genetics opts into co-development of this clinical program, we add another potential product to our strong pipeline,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics.
“Together with Genmab, we look forward to advancing tisotumab vedotin for the treatment of solid tumors,” Siegall further noted.
Solid Tumor Indication
The GEN 701 study (NCT02001623) is ongoing and further data, including other solid tumor indications, will be published at a later date.
“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,”said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics.
“The encouraging [data from this trial] 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.”
“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,” Drachman added.
Tisotumab vedotin was evaluated in a phase I/II 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% had received prior treatment with a platinum and/or taxane-based chemotherapy regimen and 71% had received prior bevacizumab (Avastin®; Genentech/Roche).
Key findings include:
- Of the 34 patients evaluable for response, 11 patients (32%) 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%), epistaxis, fatigue and alopecia (47% each) and nausea (44%).
- The most common grade 3 or higher adverse events were vomiting (15%) and fatigue, nausea and abdominal pain (9% each).
- Ocular events of any grade occurred in 53% 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.