Trodelvy Plus Keytruda May Slow Progression in mTNBC

Trodelvy plus Keytruda was associated with an improvement in disease progression in mTNBC: © stock.adobe.com.

Among patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors express PD-L1, Trodelvy (sacituzumab govitecan-hziy) plus Keytruda (pembrolizumab) has been associated with a significant improvement in progression-free survival compared with Keytruda and chemotherapy treatment, according to recently announced study results.

Topline results from the phase 3 ASCENT-04/KEYNOTE-D19 study were announced in a news release from Gilead Sciences, Inc., noting that in the study the combination of Trodelvy and Keytruda showed a statistically significant and clinically meaningful improvement in progression-free survival.

Additionally, the safety profile of Trodelvy plus Keytruda was found to be consistent with the known safety profile of each treatment, according to the news release.

“These findings are the first to show the transformative potential of an antibody-drug conjugate combined with an immuno-oncology agent in early treatment lines of metastatic breast cancer,” Dr. Dietmar Berger, chief medical officer of Gilead Sciences, said in the release. “For patients with this difficult to treat type of breast cancer, these results potentially offer a new pathway that may redefine their treatment options.”

Overall survival data were not mature at the time of the progression-free survival primary analysis, but the news release noted that there was an early trend showing improvement in overall survival among patients who received treatment with Trodelvy plus Keytruda.

Detailed results from the study, the news release stated, will be presented at a future medical meeting and discussed with regulatory authorities.

“For patients with metastatic triple-negative breast cancer, there is a critical need for more effective treatment options,” Dr. Sara Tolaney, primary investigator of the study, shared in the release. “These data suggest that the combination of [Trodelvy] and [Keytruda] may offer a new treatment approach — bringing together a potent antibody drug conjugate with immunotherapy to improve outcomes for patients.”

Tolaney is the chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, in Boston, Massachusetts, as well as the associate professor of medicine at Harvard Medical School.

Information on the ASCENT-04/KEYNOTE-D19 Study

The ASCENT-04/KEYNOTE-D19 study is a phase 3 clinical trial and has enrolled 443 patients across multiple study sites. Patients received either 10 milligrams per kilogram of Trodelvy intravenously on days 1 and 8 of a 21-day cycle plus 200 milligrams of Keytruda intravenously on day 1 of a 21-day cycle or chemotherapy plus Keytruda, with treatment continuing until disease progression or unacceptable toxicity. Patients who were randomized to receive chemotherapy were allowed to switch to receive Trodelvy if they experienced disease progression.

The study, according to its listing on clinicaltrials.gov, is still active and is estimated to be completed in February 2027.

How Antibody-Drug Conjugates Work

Dr. Yuan Yuan — a professor of medicine, director of Breast Oncology and medical director of Breast Cancer Research at Cedars-Sinai Medical Center in Los Angeles, as well as a health sciences clinical professor at UCLA — previously explained the science behind antibody-drug conjugates to CURE.

“I usually describe antibody-drug conjugates as a new class of designer drug, where the target-specific antibody was attached to a small amount of chemotherapy [payload], in contrast to conventional chemotherapy with a larger amount of drug to enter the body,” says Yuan. “Here, the idea is to do a cancer cell-specific delivery.”

Antibody-drug conjugates, Yuan explained, have a “head” made up of an antibody targeted to a receptor found on cancer cells, and that antibody is linked to a cytotoxic payload, such as a chemotherapy drug, that remains relatively stable outside of the targeted cell. Once it arrives at its delivery destination and enters the tumor cell, the linker breaks off and the drug is released.

“Then the drug can start its cytotoxic killing of the cancer cells. Then, after the drug has become effective and killed the cancer cell, it can potentially be released to the tumor microenvironment and potentially kill adjacent cells, even if those cells lack expression of that specific receptor, the so-called ‘bystander effect,’” Yuan said.

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