Trodelvy® and Keytruda® Show Significant Improvement in Survival for PD-L1+ Metastatic Triple-Negative Breast Cancer

Gilead Sciences, Inc. recently unveiled promising results from their Phase 3 ASCENT-04/KEYNOTE-D19 study, showcasing the effectiveness of Trodelvy (sacituzumab govitecan-hziy) combined with Keytruda (pembrolizumab) in treating inoperable, locally advanced, or metastatic triple-negative breast cancer (mTNBC) expressing PD-L1 (CPS ≥ 10). This study revealed that the combination of these drugs significantly enhanced progression-free survival (PFS) compared to the conventional treatment using Keytruda and chemotherapy.

The ASCENT-04/KEYNOTE-D19 trial is noteworthy as it is the first pivotal Phase 3 trial to establish the superiority of a TROP-2 antibody-drug conjugate, Trodelvy, combined with Keytruda over the standard treatment protocol in first-line metastatic TNBC. Furthermore, this combination demonstrated a promising trend towards improved overall survival (OS) for patients with previously untreated PD-L1+ (CPS ≥10) mTNBC.

The combination therapy's safety profile was consistent with the known profiles of each drug, with no new safety concerns emerging during the study. These remarkable results highlight the potential of integrating an antibody-drug conjugate with an immunotherapy agent early in the treatment of metastatic breast cancer. For patients facing this challenging type of breast cancer, these findings may introduce a novel treatment path potentially reshaping their care options.

Despite the early stage of the OS analysis, the ASCENT-04 study indicated an initial trend of improvement in OS with the Trodelvy and Keytruda combination. Continued monitoring of OS outcomes is planned, with further analyses and patient follow-ups. Gilead intends to present detailed results from this study at an upcoming medical conference and engage with regulatory authorities for further discussions.

Currently, the use of Trodelvy plus Keytruda in patients with previously untreated PD-L1+ metastatic TNBC remains investigational, and its safety and efficacy have not yet been fully established. However, the substantial and meaningful improvement in PFS observed in the ASCENT-04 study accentuates the potential of this combination as a new treatment option for patients with previously untreated inoperable PD-L1+ locally advanced or mTNBC.

Trodelvy is a standout in its field as the only approved Trop-2-directed antibody-drug conjugate demonstrating significant survival benefits in two types of metastatic breast cancers: second-line and beyond mTNBC and pre-treated HR+/HER2- metastatic breast cancer. It holds a Category 1 preferred treatment status for both conditions according to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Additionally, Trodelvy is the sole ADC with an ESMO Magnitude of Clinical Benefit Scale (MCBS) rating of 5 for mTNBC and a rating of 4 for women with HR+/HER2- metastatic breast cancer.

With a solid track record, Trodelvy has shown consistent positive results across clinical trials and in real-world scenarios involving over 50,000 patients in approximately 50 countries over five years. It has demonstrated improved outcomes in three Phase 3 breast cancer trials and is currently being tested in several ongoing clinical trials aimed at extending survival across various tumor types and disease stages.

Gilead has three ongoing Phase 3 studies involving Trodelvy across different HER2- mBC settings. These include the upcoming ASCENT-03 pivotal trial for first-line mTNBC patients not eligible for PD-L1-based therapy, the ASCENT-05 pivotal trial for early-stage TNBC patients, and the ASCENT-07 pivotal trial for HR+/HER2- mBC patients who have previously received endocrine therapy. Trodelvy is also being studied in other disease settings, including lung and gynecological cancers.

Overall, the findings from the ASCENT-04/KEYNOTE-D19 study represent a significant stride in breast cancer research, offering hope for improved treatment options for patients with this challenging condition.