ASCENT-04 Results for Frontline PD-L1+ TNBC

Key Takeaways

• Sacituzumab govitecan plus pembrolizumab was associated with longer progression-free survival than pembrolizumab plus chemotherapy in ASCENT-04/KEYNOTE-D19.
• Median progression-free survival was 11.2 months with the sacituzumab govitecan combination and 7.8 months with pembrolizumab plus chemotherapy.
• No new safety signals were reported, and discontinuation because of adverse events was lower with the sacituzumab govitecan combination.

In their ASCENT-04/KEYNOTE-D19 announcement, Gilead reported full phase 3 results showing a 35% lower risk of disease progression or death with sacituzumab govitecan plus pembrolizumab than pembrolizumab plus chemotherapy, with an HR of 0.65 and p<0.001. The study evaluated first-line sacituzumab govitecan (Trodelvy) plus pembrolizumab (Keytruda) against pembrolizumab plus chemotherapy in previously untreated disease. Eligible patients had inoperable locally advanced or metastatic triple-negative breast cancer and PD-L1-positive tumors, defined as CPS ≥10.

ASCENT-04/KEYNOTE-D19 was a global, open-label, randomized phase 3 trial that enrolled 443 patients with previously untreated, inoperable locally advanced or metastatic TNBC. Tumors were required to be PD-L1-positive, defined in the release as CPS ≥10. Patients were randomized 1:1 to sacituzumab govitecan plus pembrolizumab or pembrolizumab plus chemotherapy. Chemotherapy options were gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel, which made up the comparator regimen. Treatment continued until BICR-verified disease progression or unacceptable toxicity, and crossover to sacituzumab govitecan was allowed after progression in the chemotherapy arm. The primary endpoint was progression-free survival by blinded independent central review using RECIST v1.1.

The study met its primary endpoint; 221 patients were assigned to sacituzumab govitecan plus pembrolizumab and 222 to pembrolizumab plus chemotherapy. Median progression-free survival was 11.2 months with the sacituzumab govitecan combination and 7.8 months with pembrolizumab plus chemotherapy. The result defined the reported benefit in the PD-L1-selected first-line population. Secondary endpoints were overall survival, objective response rate, duration of response, time to onset of response, patient-reported outcomes, and safety. Together, these measures extended the assessment beyond the primary analysis.

No new safety signals were identified, and the combination was described as not worsening the known safety profiles of the individual agents. The most frequent grade 3 or higher treatment-emergent adverse events were neutropenia at 43% and diarrhea at 10% with sacituzumab govitecan plus pembrolizumab. With pembrolizumab plus chemotherapy, the most frequent high-grade events were neutropenia at 45%, anemia at 16%, and thrombocytopenia at 14%. Treatment discontinuation because of adverse events was 12% with the sacituzumab govitecan regimen and 31% with the comparator arm.