ESMO 2019: Seattle Genetics to Present Latest Study Data – Becomes Multi-product Oncology Company

The ceramic dragon fountain in the Parc Guell designed by Antoni Gaudi, Barcelona, Spain.
The ceramic dragon fountain in the Parc Guell designed by Antoni Gaudi, Barcelona, Spain.

In just over a week the annual meeting of the European Society for Medical Oncology (ESMO), to be held September 27 – October 1, 2019 in Barcelona, Spain, will start.  This year expect updates from new and ongoing trials.

The annual meeting, which brings together researchers and scientists, oncologists and oncology nurses, patient advocates, journalists and representatives from regulators and pharmaceutical industry, will focus on latest advances in oncology and translate science into better cancer patient care.

The organizers of the annual meeting noted that 3,903 abstracts were submitted for the 2019 annual meeting, representing a 16% increase over abstracts submitted for the 2018 meeting.

Program
Earlier today, Seattle Genetics confirmed that data from a number of investigational programs will be presented at the upcoming meeting.

The presentations include the first available data from a phase I clinical study of enfortumab vedotin plus pembrolizumab (Keytruda®; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.) in Locally Advanced or Metastatic Urothelial Cancer.

“We look forward to [this] presentation featuring antibody-drug conjugate enfortumab vedotin in combination with the immune therapy pembrolizumab in patients with previously untreated advanced urothelial cancer,” said Roger Dansey, MD., Chief Medical Officer at Seattle Genetics.

Antibody-drug conjugate
Enfortumab vedotin is an investigational antibody-drug conjugate which includes an anti-Nectin-4 monoclonal antibody attached to the microtubule-disrupting agent monomethyl auristatin E (MMAE). The drug uses a using proprietary linker technology developed by Seattle Genetics.

Enfortumab vedotin targets Nectin-4, a cell adhesion molecule that is expressed on many solid tumors, and that has been identified as an ADC target by Astellas.

Earlier this week the FDA accepted a Biologics License Application and Priority Review for the treatment of patients with locally advanced or metastatic urothelial cancer who have received a PD-1/PD-L1 inhibitor and who have received a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting.

Enfortumab vedotin is being co-developed by Seattle Genetics and Astellas Pharma Inc.

Tisotumab vedotin
Seattle Generics also confirmed that, during the upcoming ESMO meeting, data will be presented from tisotumab vedotin, an antibody-drug concjugate being co-developed with Genmab.

This investigation drug includes Genmab’s human antibody that binds to Tissue Factor and Seattle Genetics’ ADC technology that utilizes a cleavable linker and the microtubule disrupting agent monomethyl auristatin E (MMAE).

In cancer biology, Tissue Factor is a protein involved in tumor signaling and angiogenesis. The Tissue Factor antigen target is overexpressed in the vast majority of patients with cervical cancer and in many other solid tumors, including ovarian, lung, pancreatic, colorectal and head and neck. Based on its high expression on many solid tumors and its rapid internalization, Tissue Factor was selected as a target for an ADC approach.

Beyond ADCs: Mountaineer trial
During the upcoming ESMO meeting, new data from a clinical trial of Seattle Genetics’ novel tyrosine kinase inhibitor tucatinib (ONT-380/Array 380 ) in combination with trastuzumab (Herceptin®; Genentech/Roche) will also be presented.

Tucatinib is an orally active, reversible and selective small molecule HER2 inhibitor invented by Array Biopharma (earlier this year acquired by Pfizer) and licensed to Cascadian Therapeutics (previously named Oncothyreon) for development, manufacturing and commercialization. In March 2018, Seattle Genetics acquired Cascadian Therapeutics. However, the licensing agreement between Array Biopharma and Cascadian Therapeutics remained in effect, allowing Seattle Genetics to continue developing the novel agent.

“We are also [very] pleased to see initial results from an investigator-sponsored study called MOUNTAINEER examining the combination of our novel tyrosine kinase inhibitor tucatinib with trastuzumab for the treatment of HER2-amplified metastatic colorectal cancer,”  Dansey said.

“The development of these and other targeted medicines support our efforts toward becoming a multi-product oncology company,” he concluded.

Overview of Presentation

AbstractTitlePresenterSessionTime/DateLocation
901OEV-103: Initial results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinomaChristopher J. Hoimes, Case Western Reserve University, Cleveland, OH, USAOral Presentation Proffered Paper Session – Genitourinary tumours, non-prostateSaturday, September 28, 8:30-10:00 a.m. CESTBarcelona Auditorium, Hall 2
360PSystemic therapy in 2nd-line metastatic triple negative breast cancer (mTNBC): a systematic literature review (SLR) and meta-analysis (MA) of efficacyPeter A. Kaufman, University of Vermont Cancer Center, Burlington, VT, USAPoster PresentationSunday, September 29, 12:00-1:00 p.m. CESTBarcelona Auditorium, Hall 4
921PQuality of life of metastatic urothelial cancer (mUC) patients treated with enfortumab vedotin (EV) following platinum-containing chemotherapy and a checkpoint inhibitor (CPI): data from EV-201 cohort 1Bradley A. McGregor, Dana-Farber Cancer Institute, Boston, MA, USAPoster PresentationMonday, September 30, 12:00-1:00 p.m. CESTBarcelona Auditorium, Hall 4
1059TiPPhase 1/2 trial of tisotumab vedotin plus bevacizumab, pembrolizumab, or carboplatin in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8)Ignace B. Vergote, Leuven Cancer Institute, Leuven, BelgiumPoster PresentationSunday, September 29, 12:00-1:00 p.m. CESTBarcelona Auditorium, Hall 4
527PDTrastuzumab and tucatinib for the treatment of HER2 amplified metastatic colorectal cancer (mCRC): Initial results from the MOUNTAINEER trialJohn H. Strickler, Duke University Medical Center, Durham, NC, USAPoster Discussion Session – Gastrointestinal tumors, colorectalSunday, September 29, Poster Discussion: 3:00-3:15 p.m. CESTCordoba Auditorium, Hall 7

 

Clinical trials

  • A Study of Enfortumab Vedotin Plus Pembrolizumab and/or Chemotherapy for Patients With Urothelial Bladder Cancer (EV-103) – NCT03288545
  • Tucatinib (ONT-380) and Trastuzumab in Treating Patients With HER2+ Metastatic Colorectal Cancer – NCT03043313