‘Encouraging’ Data on Sacituzumab Govitecan in Endometrial Cancer

Preliminary results of a phase II investigator-initiated trial (IIT) presented at the American Society of Clinical Oncology (ASCO) annual meeting demonstrated the clinical activity of the antibody-drug conjugate (ADC) sacituzumab govitecan (Trodelvy) in patients with recurrent endometrial cancer and Trop-2 overexpression.

Sacituzumab govitecan, a humanized anti-Trop-2 antibody conjugated with the active metabolite of irinotecan, is FDA approved in metastatic urothelial cancer and triple-negative breast cancer.

In this exclusive MedPage Today video, investigator Alessandro Santin, MD, of the Yale University School of Medicine in New Haven, Connecticut, discusses the design of the endometrial cancer study as well as the significance of the results.

Following is a transcript of his remarks:

Just a little bit of background. Endometrial cancer is the most common gynecological cancer in the United States, as well as Europe. And over 13,000 women in the U.S. alone will die this year from recurrent endometrial carcinoma. When these patients fail standard salvage treatment in the form of chemotherapy — such as carboplatin and paclitaxel — and immune checkpoint inhibitors, the possibility of effective treatments are very, very limited.

That is why we designed this trial, this phase II trial — specifically targeting this population that had failed both chemotherapy as well as immune checkpoint inhibitors — using this novel antibody-drug conjugate that targets Trop-2 as a surface glycoprotein. And this again, is a monoclonal antibody targeting the trophoblast 2 on the surface, with attached to it a linker that is cleavable. And so this ADC is able to release, when it’s internalizing inside Trop-2-positive tumor cell, its toxic payload that is called SN-38 — that is a derivative of irinotecan. So a chemotherapeutic agent that is commonly used in [gastrointestinal] cancer.

So this novel ADC is currently approved already for two indications in the U.S., in breast cancer patients as well as with one indication in urothelial cancer patients in the U.S., with the name of Trodelvy.

So what did we find? So we enrolled all patients with endometrial cancer with an epithelial endometrial cancer such as endometrioid histology, uterine serous, clear cell, as well as carcinosarcoma. And we treated these patients with this regimen 10 mg/kg day 1 and day 8 every 3 week cycles, until again either toxicity or progression. Out of the 21 patients evaluable, we found that seven of these patients had a response. So either a complete or a partial response, for a response rate of 33.3%. Very promising considering that salvage chemotherapy in this setting, they have usually response rate in the range of 10% to 15%.

So the progression-free survival in the first stage was 5.7 months. And so far, again, the overall survival is 22 months. But these data of course, are maturing as we speak because I’m currently referring to 21 patients enrolled in the stage one.

So this was a Simon two-stage design, meaning that the plan was to enroll 21 evaluable patients in the first stage. If three or more responded with a CR [complete response] or PR [partial response], the first stage was considered positive and the second stage would have been activated. So, because we found that not three, but seven patients responded with either a CR or PR, the study is now open to the second stage.

Another important thing that I need to mention is that unlike the [TROPiCS-03] that I also presented at the meeting, this study enriched the patient population, in terms of eligibility criteria, looking to Trop-2 expression by immunohistochemistry, meaning that only patients with an expression of Trop-2 in at least 50% of the tumor cells were allowed to enroll in this IIT. And this is different from [TROPiCS-03] that allowed enrollment of all-comer patients with endometrial recurrent disease.

So data are very encouraging. We are very excited about this preliminary result. And the second stage has just started at Yale University, enrolling a second group of 29 patients to get to a total of 50.