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This year’s San Antonio Breast Cancer Symposium (SABCS) is taking place on December 5-9th, 2017, and it is expected to bring in a broad international audience of researchers and physicians to discuss the future of breast cancer research and treatment. Many exciting abstracts and posters will be presented and discussed during the conference, many of which are turning their focus toward precision and targeted therapeutics that have changed the way we look at cancer treatment in the past several decades.

Much of today’s cancer research developments are being made in targeted therapy spaces, such as antibody-drug conjugates or ADCs. At SABCS, the exciting presentations and posters dealing with ADCs, and other targeted therapeutics, are expected to provide invaluable information to physicians and researchers that are dealing with hard-to-treat patient populations that need more potent and better tolerable treatment options than what are currently available. A summary of notable presentations and posters dealing with targeted therapeutics at SABCS can be found here.

For an overview of oral and poster presentations about antibody-drug conjugates (ADCs) to be presented during the annual San Antonio Breast Cancer Symposium, December 5-9, 2017, Click here.

Sacituzumab govitecan (IMMU-132)
A general session at San Antonio breast cancer symposium will focus on Sacituzumab govitecan (IMMU-132), a novel ADC that is being investigated in as >3rd line therapy for patients with relapsed/refractory metastatic triple negative breast cancer (mTNBC). The data from this study will be presented and discussed on Wednesday, December 6th, at 11:00am in Hall 3. (Abstract GS1-07)

Previously, Sacituzumab govitecan was granted Breakthrough Designation based on promising data seen in a phase I/II basket trial for patients with multiple, advanced epithelial cancers. Breakthrough therapy designation is granted in order to expedite the development and review of treatments that may demonstrate substantial benefit over the current available treatments, so patients with serious, life-threatening diseases can have access to them treatments as soon as possible.

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The ADC has received FDA Fast Track designation for the treatment of patients with triple-negative breast cancer, small-cell and non-small-cell lung cancers, and has also been designated an orphan drug for the treatment of patients with small-cell lung or pancreatic cancer in the U.S., and for the treatment of patients with pancreatic cancer in the European Union. [1] Now, Sacituzumab govitecan has been evaluated for use as a single agent for patients with metastatic triple negative breast cancer who have no other treatment options to turn to.

Metastatic triple-negative breast cancer is an aggressive breast cancer type that currently has very limited treatment options.  After the first line therapy, median overall survival for this disease is 6-13 months, and median progression free survival is typically 3-4 months. [2]

Sacituzumab govitecan targets Trop-2, which is expressed in over 90% of triple negative breast cancer, as well as most epithelial cancers, and delivers SN-38, the active metabolite of irinotecan. In the study that will be discussed at SABCS, 110 metastatic triple negative breast cancer patients saw an overall response rate of 34%, a clinical benefit rate of 46% and a progression free survival of 7.6 months. These promising results have led to the ADC’s submission for consideration of accelerated approval.

A randomized global confirmatory phase III trial using Sacituzumab govitecan is currently underway, and the drug is also being evaluated for use in combination with other drugs in triple negative breast cancer and other breast cancer subsets. To learn more about sacituzumab govitecan, and to follow ongoing clinical trials, click here.[3]

Later in the week at SABCS, researchers at Daiichi Sankyo will take part in a poster discussion session,  where attendees will learn about the latest findings from an ongoing phase I study of DS-8201a, an ADC under investigation in HER2 breast cancers. DS-8201 uses a novel linker to deliver a topoisomerase I inhibitor, and has a high drug to antibody ratio of (8:1).

In pre-clinical studies, DS-8201 has shown efficacy when used in adotrastuzumab emtansine (T-DM1) resistant HER2 breast cancer, as well as breast cancer that is low in HER2 expression. Now, researchers are focused on a current phase I trial in patients with breast cancer, gastric cancer, and other HER2 expressing tumors. The breast cancer patient cohort will be the focus of the poster discussion on Thursday, December 7th, at 7am in the Stars st Night Ballrooom 1 & 2. (Abstract #1094)

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [4]

In the current trial (NCT02564900), 146 patients are being treated in two phases, a dose escalation part 1, and a dose expansion part 2. Part 2 of this study involved 46 patients with breast cancer that have received an average of five prior regimens in the metastatic setting. Since these patients are in the metastatic stage and significantly pre-treated, targeted therapeutics like DS-8201a become extremely important, as they are left with little to no treatment options.

DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer (NCT02564900)

The available results have shown that DS-8201a is well-tolerated and has significant activity for patients that were pre-treated with T-DM1/ pertuzumab, as well as in patients with low expressing HER2 breast cancer. For these patients, an overall response rate of 41% was observed. In a cohort of patients had received prior T-DM1, treatment with DS-8201a achieved a higher Overall Response Rate (ORR) of 41% compared to the reported response these patients had to their prior T-DM1 treatment with an ORR of 23%. In the subset of 24 pts from cohort 2a who had received prior treatment with pertuzumab and T-DM1, the confirmed ORR was 44%. [5]

“The initiation of this Phase II study represents an important next step to rapidly advance the development of DS-8201, as we will obtain a better understanding of how the smart delivery of chemotherapy directly to targeted cancer cells may help patients with HER2-expressing metastatic breast cancer,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo.

Future of Breast Cancer Research 
In addition to the discussions taking place over antibody-drug conjugates at this year’s San Antonio Breast Cancer Symposium, there are numerous posters that cover other targets therapeutics being developed and evaluated. The San Antonio Breast Cancer Symposium is designed to provide state-of-the-art information on the latest therapeutic options and challenges being researched in breast cancer and pre-malignant breast disease, to an international audience of  physicians and researchers.

Targeted therapeutics are undoubtedly making a strong appearance at this year’s meeting, and are expected to continue to revolutionize the way we treat breast cancer. A complete summary of the other exiting posters in the area of targeted therapeutics can be found here.

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