Gosatuzumab combined with pembrolizumab improves PFS in patients with metastatic triple-negative breast cancer

In theASCENT-04/KEYOTE-D19 study (NCT05382286),gosatuzumab/TrodelvyGAPA Pembrolizumab met its primary endpoint, demonstrating a clinically meaningful improvement in progression-free survival (PFS) in patients with PD-L1-expressing metastatic triple-negative breast cancer (mTNBC).

Triple-negative breast cancer is an aggressive subtype with few treatment options because the tumor cells lack human epidermal growth factor receptor2, progesterone and estrogen receptors. When these receptors are missing, there is little response to standard chemotherapy, hormone therapy, endocrine therapy and immunotherapy. By combining the cytotoxic potential of chemotherapy with the accuracy of monoclonal antibodies, antibody-drug conjugates (ADCs), such as gosatuzumab, offer a revolutionary approach to treating TNBC.

FormTNBC patients, there is an urgent need for more effective treatment options. These data suggest that the combination of gosatuzumab and pembrolizumab may offer a new treatment approach that combines a potent antibody drug with immunotherapy to improve patient outcomes. Gosatuzumab is an ADC that was first approved by the U.S. Food and Drug Administration in 2021 as a monotherapy for the treatment of patients with unresectable locally advanced or mTNBC who have received 2 or more prior systemic therapies. The decision was based on data from the ASCENT phase 3 trial (NCT02574455), which showed that treatment with SG produced a greater PFS benefit compared with single-agent chemotherapy.

In the global open-label, randomized phase 3 ASCENT-04 trial, researchers evaluated the efficacy and safety of gosatuzumab plus pembrolizumab versus chemotherapy plus pembrolizumab in 443 patients with mTNBC expressing PD-L1. They were randomized 1:1:1 to receive 10 mg of gosatuzumab per kilogram intravenously on days 1 and 8 of a 21-day cycle, 200 mg of pembrolizumab intravenously on day 1 of a 21-day post-cycle, or receive chemotherapy (gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel) plus pembrolizumab. The primary endpoint is PFS, and secondary endpoints are overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PRO), and safety.

Preliminary analysis of trial data shows that gosatuzumab plus pembrolizumab has a greater benefit on PFSthan chemotherapy plus pembrolizumab. Although OS data were immature at the time of PFS analysis, early trends of improvement compared with standard of care were observed. The lead investigators also noted that the safety profile was consistent with the known profile of gosatuzumab and pembrolizumab.

These findings demonstrate for the first timethe transformative potential of combining ADCs with immunogenic agents in the early-stage treatment of metastatic breast cancer. These results may provide a new way to redefine treatment options for patients with this difficult-to-treat cancer.

References:https://www.pharmacytimes.com/view/sacituzumab-govitecan-hziy-plus-pembrolizumab-improves-pfs-in-patients-with-metastatic-triple-negative-breast-cancer