Date: 2017-09-08
Type of
information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2017 Congress
Company: Genmab (Denmark)
Product: tisotumab vedotin (HuMax-TF-ADC)
Action
mechanism:
- antibody drug conjugate. Tisotumab vedotin is an antibody-drug conjugate (ADC) composed of a human antibody that binds to tissue factor conjugated to Seattle Genetics' clinically validated cytotoxic drug MMAE. Tissue factor is a protein involved in tumor signaling and angiogenesis. Based on its high expression on many solid tumors and its rapid internalization, this protein was selected as a target for an ADC approach. Tisotumab vedotin is in Phase I/II clinical development for solid tumors in two studies (GEN701 and GEN702).
- Genmab has a license and collaboration agreement for tisotumab vedotin with Seattle Genetics under which Seattle Genetics has the right to exercise a co-development option at the end of Phase I clinical studies.
Disease: solid tumors (ovarian cancer, cervical cancer, endometrium cancer, bladder cancer, prostate cancer, esophageal cancer, lung cancer)
Therapeutic
area: Cancer - Oncology
Country: Belgium, Denmark, Sweden, UK, USA
Trial
details:
- The GEN701 study is a 173 patient, two-part Phase I/II study of tisotumab vedotin in seven types of solid tumors: ovarian, cervical, endometrium, bladder, prostate, esophageal, and lung. Part 1 was a classical 3+3 dose escalation design testing various doses of tisotumab vedotin once every three weeks to establish the recommended Phase II (RP2D) and maximum tolerated dose as well as the safety profile of tisotumab vedotin. The still ongoing Part 2 of the study investigates all seven indications in parallel expansion cohorts. Patients receive 2.0 mg/kg (=RP2D) of tisotumab vedotin once every three weeks. The primary objective of this part of the study is to further investigate the safety profile of tisotumab vedotin and preliminary efficacy. (NCT02001623)
Latest
news:
- • On September 8, 2017, Seattle Genetics announced that preliminary clinical data for tisotumab vedotin from phase 1/2 clinical trial (GEN701) are being featured in an oral presentation and in a poster session at the European Society for Medical Oncology (ESMO) Congress.
- Among patients with cervical cancer treated in the trial, tisotumab vedotin demonstrated an encouraging response rate and manageable safety profile. 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.
- 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. Seattle Genetics and Genmab are now evaluating next steps in the development of tisotumab vedotin for cervical cancer.
- • On June 16, 2017, Genmab announced preliminary data from the ongoing Phase 1/2 study of tisotumab vedotin in solid tumors (GEN701). In Part 2 of the study, 11 of 34 evaluable patients in the cervical cancer cohort achieved a response; with a median time of treatment of 4.9 months, 7 responders are still ongoing or in follow up for progression. The safety profile of tisotumab vedotin was consistent with known MMAE based antibody-drug conjugates (ADC), including peripheral neuropathy and neutropenia. Additionally, conjunctivitis was identified as a tisotumab vedotin specific toxicity, which led to introducing of prophylactic management. In the cervical cancer cohort, 15 patients experienced one or more Grade 3 adverse events: gastro-intestinal related (5 patients), anemia (2 patients), infections (1 patient), neuropathy (2 patients), bleeding (2 patients), other (10 patients). Genmab is considering plans for further clinical development of tisotumab vedotin in cervical cancer. The GEN701 study is ongoing and further data in both cervical cancer and other solid tumor indications will be published at a later date. Genmab intends to submit data from this study for presentation at an upcoming medical conference.
Is
general: Yes
