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Sylvester Researcher Reports Early, Promising Results of New Therapy in Several Cancers

The first study in humans to explore the potential of a new treatment for solid tumors shows acceptable safety, an effective dose range and — although not designed to do so — demonstrates that tisotumab vedotin can shrink tumors in patients with advanced or metastatic bladder, prostate, ovarian and other cancers, researchers report.

Brian M. Slomovitz, M.D.

“As the only academic medical center in South Florida, we are committed to offering the best standard approaches to therapy, as well as to conducting early research studies like this to identify promising cancer treatments going forward,” said Brian Slomovitz, M.D., director of the Division of Gynecologic Oncology at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.

Tisotumab vedotin, a human antibody drug conjugate, targets tissue factor on the surface of many different kinds of tumor cells. In addition to being common, expression of tissue factor is associated with worse outcomes for people with cancer. The study, published in Lancet Oncology, demonstrates promise across cancer types, but particularly among women with advanced cervical cancer.

“We need to do these early phase studies, and we need to do them across disease sites in order to see which ones are going to work,” Dr. Slomovitz said. “There are rationales why it works in cervical cancer, but you never know that until you actually evaluate it in the clinic.”

As a co-author of the international, multicenter trial, Dr. Slomovitz helped design the research, enroll patients and prepare the Lancet Oncology manuscript. Sylvester contributed the second highest number of participants in the United States.

“I’m thrilled we’re further investigating a drug that might work in cervical cancer,” Dr. Slomovitz said. This form of malignancy is less common and less often studied than ovarian or endometrial cancer, he explained, and there is an unmet need for treatment of metastatic cervical cancer.

The current InnovaTV 201 study focused on safety and efficacy in two phases. Investigators first assigned 27 adults with advanced or metastatic tumors to one of eight doses of tisotumab vedotin. In an expanded second phase, they evaluated this agent in 147 people with cancer of the ovary, cervix, endometrium, bladder, prostate, and esophagus, non-small cell lung cancer, and squamous cell carcinoma of the head and neck.

Tisotumab vedotin binds to tissue factor on the outside of a tumor cell, forms a complex that enters the cell and delivers what researchers describe as a “toxic payload.” The result is the cleaving of the lysosome and release of a factor called monomethyl auristatin E (MMAE) that disrupts essential functions and leads to tumor cell death.

The results validate the targeting of tissue factor in people with certain advanced cancers, the researchers wrote, and demonstrate this agent’s “encouraging antitumor activity in heavily pretreated patients.” The safety profile of tisotumab vedotin 2?0 mg/kg once every 3 weeks was generally consistent with other MMAE-based antibody-drug conjugates as well, although epistaxis and conjunctivitis seem to be more frequent with tisotumab vedotin than with previously assessed drugs of this type.

Tisotumab vedotin is being developed in collaboration with Seattle Genetics, Inc. and Genmab. “The early efficacy results seem very promising, and I’m excited the sponsor is moving forward with future studies in cervical cancer,” Dr. Slomovitz said.

In fact, full results from the cohort of women with previously treated recurrent or metastatic cervical cancer from the current Phase 2 study were just presented at the Society of Gynecologic Oncology in Honolulu, Hawaii.

Also, a larger Phase 2 trial of the agent in women with this tumor type is already underway in cooperation with the non-profit research consortium Gynecologic Oncology Group Foundation.

“We’re not going to be satisfied until all women with advanced recurrent cervical cancer — or all women with cervical cancer, for that matter — don’t die from their disease,” he added.

Sylvester Comprehensive Cancer Center offers a number of active clinical trials that aim to drive progress in diagnosis and treatment of cancer.

Tags: Brian Slomovitz, Genmab, Gynecologic Oncology Group Foundation, Inc., Seattle Genetics, Society of Gynecologic Oncology, Sylvester Comprehensive Cancer Center, tisotumab vedotin