Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study.
Bibliographic record
Abstract
LBA109 Background: Although PD-1/PD-L1 inhibitors plus chemo have expanded treatment options for previously untreated PD-L1–positive advanced TNBC, there still remains a critical unmet need to improve outcomes. SG previously demonstrated significant clinical benefit in pretreated metastatic TNBC (mTNBC). We report results from the ASCENT-04/KEYNOTE-D19 study in patients with previously untreated, PD-L1–positive (CPS ≥ 10; 22C3 assay) locally advanced unresectable or mTNBC. Methods: Patients were randomized 1:1 to SG (10 mg/kg IV, day 1 & 8) + pembro (200 mg, day 1, max 35 cycles) in 21-day cycles or chemo (gemcitabine + carboplatin, paclitaxel, nab-paclitaxel) + pembro until disease progression or unacceptable toxicity. Randomization was stratified by curative treatment-free interval, geography, and prior exposure to anti–PD-(L)1 therapy in the curative setting. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). Key secondary endpoints include overall survival (OS); objective response rate (ORR) and duration of response (DOR) by BICR; and safety. Results: 443 patients were randomized at a 1:1 ratio: 221 to SG + pembro and 222 to chemo + pembro. The median follow-up was 14 mo. SG + pembro showed a significant improvement in PFS by BICR compared with chemo + pembro (hazard ratio [HR], 0.65; 95% CI, 0.51-0.84; P = .0009; Table). Median DOR was 16.5 mo for SG + pembro vs 9.2 mo for chemo + pembro (Table). Although OS data were immature, a positive early trend in OS improvement was also noted. The most frequent (≥ 10% of patients) grade ≥ 3 treatment-emergent adverse events (TEAEs) with SG + pembro were neutropenia (43%) and diarrhea (10%); and with chemo + pembro were neutropenia (45%), anemia (16%), and thrombocytopenia (14%). Conclusions: SG + pembro led to a statistically significant and clinically meaningful improvement in PFS vs chemo + pembro with durable responses, no new safety concerns for SG or pembro, and a lower rate of treatment discontinuation due to TEAEs in patients with previously untreated, PD-L1–positive advanced TNBC. These data support the use of SG + pembro as a potential new standard of care treatment in this patient population. Clinical trial information: NCT05382286 . Efficacy, BICR, intent-to-treat SG + pembro(n = 221) Chemo + pembro(n = 222) Median PFS (95% CI), mo 11.2 (9.3-16.7) 7.8 (7.3-9.3) HR (95% CI); P -value (adjusted for randomization stratification factors) 0.65 (0.51-0.84); P = .0009 ORR (95% CI), % 59.7 (52.9-66.3) 53.2 (46.4-59.9) Median DOR (95% CI), mo 16.5 (12.7-19.5) 9.2 (7.6-11.3) Safety (TEAEs), all treated, n (%) n = 221 n = 220 Any grade; grade ≥ 3 220 (> 99); 158 (71) 219 (> 99); 154 (70) Led to dose reduction 78 (35) 96 (44) Led to any treatment discontinuation 26 (12) 68 (31)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".