In August 2017, Seattle Genetics opted into a development partnership for an antibody-drug conjugate developed by Genmab as part of a collaboration seven years in the making. A year and a half later, researchers have pulled the curtain back on some early results that might justify their enthusiasm for tisotumab vedotin.
In a Phase I/II trial involving 147 patients — spanning 6 different cancer types — who have become resistant to an average of three types of prior treatments, the ADC is found to yield responses in a “significant minority,” meaning their tumors either shrank or stopped growing. The responses lasted an average of 5.7 months, with the top of the range reaching 9.5 months, according to the research team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust.
Described as a “Trojan horse,” the ADC works by binding to a receptor that’s abundant on the surface of cancer cells called tissue factor (the antibody’s job) then releasing a cytotoxic payload (the drug part) to kill the cancer cells from within.
Investigators reported “good responses” and “manageable side effects” for heavily pre-treated patients in the study — with the exception of prostate cancer, where there were none.
- Bladder cancer: 27%
- Cervical cancer: 26.5%
- Ovarian cancer: 14%
- Esophageal cancer: 13%
- Non-small cell lung cancer: 13%
- Endometrial cancer: 7%
“We have already begun additional trials of this new drug in different tumour types and as a second-line treatment for cervical cancer, where response rates were particularly high,” said professor Johann de Bono, head of clinical studies at ICR. “We are also developing a test to pick out the patients most likely to respond.”
Tisotumab vedotin adds to the slate of ADCs on offer at Seattle Genetics, including its blockbuster franchise drug Adcetris as well as enfortumab vedotin, which is going through a pivotal Phase II with a “breakthrough” badge bestowed by the FDA.
Seattle Genetics and Genmab sponsored the study, which was published today in The Lancet Oncology.
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