European Commission Approves Gilead's Trop-2 ADC Trodelvy Plus Keytruda for First-Line PD-L1-Positive Metastatic Triple-Negative Breast Cancer

A CPS 10 gate on the immunotherapy side

The new indication is written to a PD-L1 combined positive score of at least 10, the same cut-off pembrolizumab has carried in metastatic TNBC since KEYNOTE-355. Gilead's release does not name the assay. In the United States, where the FDA has already approved the same combination, the label ties eligibility to CPS 10 "as determined by an FDA-authorized test," and the agency's companion-diagnostic list carries Dako's PD-L1 IHC 22C3 pharmDx for TNBC at that threshold, cleared for pembrolizumab on Nov. 13, 2020.

The U.S. indication also allows the ADC with pembrolizumab and berahyaluronidase alfa, the subcutaneous Keytruda Qlex formulation, while the European text quoted by Gilead covers pembrolizumab only.

ASCENT-04, 443 patients, 11.2 versus 7.8 months

ASCENT-04 randomized 443 previously untreated patients with PD-L1-positive disease, 221 to Trodelvy plus pembrolizumab and 222 to chemotherapy plus pembrolizumab. Median progression-free survival was 11.2 months against 7.8 months, a hazard ratio of 0.65 with p below 0.001. Grade 3 or worse neutropenia ran at 43% on the ADC arm and 45% on chemotherapy, but discontinuations for adverse events were 12% against 31%. The results were presented at ASCO in 2025 and published in the New England Journal of Medicine with Sara Tolaney, M.D., M.P.H., of Dana-Farber Cancer Institute as principal investigator.

"This regimen helps redefine a standard of care by offering a novel first-line treatment option for a metastatic patient population with a particularly aggressive form of breast cancer," said Evandro de Azambuja, M.D., Ph.D., head of the medical support team at the Jules Bordet Institute and an ASCENT-04 investigator.

June's monotherapy approval, now paired

Two months earlier the Commission had approved Trodelvy as monotherapy for first-line patients who are not candidates for PD-1 or PD-L1 inhibitors, on ASCENT-03. That trial used a crossover design that let chemotherapy patients receive the ADC after progression, and the EU accepted it on progression-free survival. Gilead had disclosed at the time that the ASCENT-04 filing was already under review at the European Medicines Agency.

Mika Kakefuda Derynck, M.D., Gilead's senior vice president of clinical development in oncology, said: "With Trodelvy-based options now approved in the EU for all eligible first-line metastatic TNBC patients across PD-L1 status, we have established a new, much-needed backbone therapy."

Gilead counts more than 75,000 breast cancer patients treated with the drug since 2020. Its U.S. label also flags patients homozygous for the UGT1A1*28 allele, who had grade 3 or 4 neutropenia at 57% against 41% for wild-type homozygotes, a pharmacogenetic detail the European release repeats without recommending pre-treatment genotyping.

Why This Matters to the APO|APE Reader

Every first-line metastatic TNBC patient in Europe now routes through one PD-L1 stain to two different Trodelvy regimens, which puts the CPS 10 call, and the scorer's handling of tumor cells plus immune cells that the combined positive score demands, directly in the treatment path from the first biopsy. In the ASCENT-03 population the drug is given without an immunotherapy partner, so a false-negative PD-L1 result no longer costs a patient the ADC but does cost the pembrolizumab. The 22C3 clone has held this gatekeeping role in the U.S. for nearly six years; Europe has now built the same dependency into its label without naming the test.