Sacituzumab Govitecan Plus Pembrolizumab Improves PFS in PD-L1+ TNBC
ASCENT-04 data showed sacituzumab govitecan plus pembrolizumab improved progression-free survival in PD-L1+ metastatic triple-negative breast cancer.
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The combination of sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) significantly improved progression-free survival (PFS) compared with pembrolizumab and chemotherapy when used for the treatment of patients with inoperable, locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥ 10), meeting the primary end point of the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286).1
Topline results from the ASCENT-04/KEYNOTE-D19 study also showed the safety profile of sacituzumab govitecan plus pembrolizumab to be consistent with the known safety profile of each agent, with no new safety signals observed.
Further, overall survival (OS), one of the trial’s secondary end points, was not mature at the time of the PFS primary analysis. However, an early trend in improvement for OS with the combination was seen, and investigators will continue monitoring OS outcomes.
“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,” stated Dietmar Berger, MD, PhD, chief medical officer of Gilead Sciences, in a press 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.”
Patient follow-up is ongoing and further analyses are planned. Additionally, full data from the study are expected to be presented at an upcoming medical meeting and shared with regulatory authorities.
Behind the ASCENT-04/KEYNOTE-D19 Study
The global, open-label, randomized, phase 3 ASCENT-04/KEYNOTE-D19 study is assessing the efficacy and safety of sacituzumab govitecan given in combination with pembrolizumab vs pembrolizumab plus chemotherapy for the treatment of patients with previously untreated, inoperable locally advanced or metastatic TNBC whose tumors express PD-L1.1,2
Enrollment in the study was open to patients with an ECOG performance status score of 0 or 1 and adequate organ function. Patients of childbearing potential were required to use protocol-specified method(s) of contraception, and those with HIV must have been on antiretroviral therapy and have a well-controlled HIV infection/disease.2
A total of 443 patients were enrolled across multiple study sites and randomly assigned in a 1:1 fashion to receive either treatment with sacituzumab govitecan given at a dose of 10 mg/kg via intravenous (IV) infusion on days 1 and 8 of a 21-day cycle, plus IV pembrolizumab at a dose of 200 mg on day 1 of a 21-day cycle, or chemotherapy plus pembrolizumab. Included in the chemotherapy regimen was gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel.1
Patients continued to receive treatment until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity. For those who were randomly assigned to receive chemotherapy, patients were permitted to crossover and receive sacituzumab govitecan if they had disease progression.
PFS as determined by BICR using RECIST v1.1 served as the primary end point of the study. Secondary end points consisted of OS, objective response rate, duration of response, time to onset of response, patient-reported outcomes, and safety.
About Sacituzumab Govitecan
Sacituzumab govitecan is a Trop-2-directed antibody-drug conjugate (ADC) that first received FDA approval in April 2020. The ADC was evaluated in the ASCENT trial (NCT02574455) where its safety and efficacy were compared with physicians' choice of chemotherapy.3
The agent has demonstrated meaningful survival advantages in patients with advanced triple-negative breast cancer who have received 2 or more prior systemic therapies, at least 1 of which was in the metastatic setting. It is also approved in hormone receptor-positive (HR+)/HER2-negative (–) advanced disease given prior endocrine therapy and at least 2 additional systemic therapies, and pretreated HR+/HER2– metastatic breast cancer.1 Sacituzumab govitecan a Category 1 preferred treatment for both indications per the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines), and marks the only ADC with an ESMO Magnitude of Clinical Benefit Scale rating of 5 for metastatic TNBC.
Three phase 3 studies are currently ongoing to evaluate treatment with sacituzumab govitecan across HER2– metastatic breast cancer. The first is the upcoming ASCENT-03 trial (NCT05382299) in first-line patients with metastatic TNBC who are not candidates for PD-L1-based therapy. Second is the pivotal ASCENT-05 trial (NCT05633654) in patients with early-stage TNBC. Last is the ASCENT-07 study (NCT05840211) in patients with HR+/HER2– metastatic breast cancer who have received endocrine therapy.
Other disease states also have clinical trials ongoing to evaluate sacituzumab govitecan, including in lung and gynecological cancers.
