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KOL Pulse · Clinical Evidence

Metastatic TNBC: Cross-Trial FDA Approval Comparison

Every pivotal FDA-registration trial in metastatic triple-negative breast cancer — approval dates, biomarker & companion-diagnostic wording, and PFS/OS — with each figure traced to a live primary source.

Compiled by the KOL Pulse research team with a Claude Science skill · sources: openFDA / Drugs@FDA · ClinicalTrials.gov · PubMed.

Metastatic TNBC — Cross-Trial Comparison of FDA-Registration Trials

Most recent first. FDA action → Drugs@FDA overview; PMID → PubMed; NCT → ClinicalTrials.gov. Approval dates from Drugs@FDA submission histories; biomarker/CDx wording from openFDA SPL labels; efficacy from cited publications.
New 2026 approval Active Withdrawn Negative HER2-low parallel pathway
FDA dateDrug / trialPopulation / comparatorBiomarker & companion DxMedian PFSMedian OSFDA action / statusPub.
2026-06-24 Sacituzumab govitecan (Trodelvy) + pembrolizumab
ASCENT-04 / KEYNOTE-D19 · NCT05382286
Gilead Sciences · N=443 · 1L
Previously untreated PD-L1-positive locally advanced unresectable/metastatic TNBC
vs Pembrolizumab + chemo (physician's choice)
PD-L1 CPS ≥10
Label: PD-L1 (CPS ≥10) "as determined by an FDA-authorized test" (22C3 pharmDx). SG is Trop-2-directed (no Trop-2 test).
11.2 vs 7.8 mo, HR 0.65 (95% CI 0.51–0.84, P<0.001) Immature at analysis Approved 1L mTNBC, PD-L1 CPS≥10 (SG + pembrolizumab)
ACTIVE – NEW 1L combination indication
Tolaney SM et al. N Engl J Med 2026;394:354–66 (PMID 41564397)
2026-06-24 Sacituzumab govitecan (Trodelvy) monotherapy
ASCENT-03 · NCT05382299
Gilead Sciences · N=558 randomized (623 registered) · 1L
Previously untreated advanced TNBC, not candidates for PD-1/PD-L1 inhibitors
vs Chemo (paclitaxel/nab-paclitaxel/gem-carbo)
None required (Trop-2 ADC; enrolled CPS<10 and IO-ineligible CPS≥10)
No companion diagnostic. Clinical eligibility: "not candidates for PD-1 or PD-L1 inhibitor-based therapy."
9.7 vs 6.9 mo, HR 0.62 (95% CI 0.50–0.77, P<0.001) Immature at analysis Approved 1L mTNBC single agent (PD-1/PD-L1-ineligible)
ACTIVE – NEW 1L single-agent indication
Cortés J et al. N Engl J Med 2025;393:1912–25 (PMID 41124233)
2026-05-22 Datopotamab deruxtecan (Datroway)
TROPION-Breast02 · NCT05374512
AstraZeneca / Daiichi Sankyo · N=644 · 1L
Previously untreated locally recurrent inoperable/metastatic TNBC, immunotherapy not an option
vs Chemo (investigator's choice)
None required (Trop-2 ADC; stratified by PD-L1 status)
No companion diagnostic. Clinical eligibility: "not candidates for PD-1/PD-L1 inhibitor therapy."
10.8 vs 5.6 mo, HR 0.57 (99% CI 0.44–0.73, P<0.0001) 23.7 vs 18.7 mo, HR 0.79 (95.01% CI 0.64–0.98, P=0.029) — significant Approved 1L mTNBC (PD-1/PD-L1-ineligible)
ACTIVE – NEW 1L single-agent indication (2nd Trop-2 ADC in this setting)
Dent R et al. Ann Oncol 2026 (PMID 41937088)
2022-08-05 Trastuzumab deruxtecan (Enhertu)
DESTINY-Breast04 · NCT03734029
AstraZeneca / Daiichi Sankyo · N=557 (63 HR-negative, 11.3%) · 2L+ (post-chemo)
HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer; small HR-negative cohort is the TNBC-relevant slice
vs Chemo (physician's choice: eribulin/capecitabine/gemcitabine/paclitaxel/nab-pac)
HER2-low (IHC 1+ or IHC 2+/ISH-)
Label: HER2-low "as determined by an FDA-authorized test" (HER2 IHC, e.g. PATHWAY/VENTANA & HercepTest). Reclassifies ~60% of traditional TNBC out of the TNBC-ADC pathway.
All pts 9.9 vs 5.1 mo, HR 0.50 (P<0.001); HR-negative subgroup 8.5 vs 2.9 mo, HR 0.46 (exploratory) All pts 23.4 vs 16.8 mo, HR 0.64; HR-negative subgroup 18.2 vs 8.3 mo, HR 0.48 (exploratory) Approved HER2-low MBC (incl. HR-negative)
ACTIVE – HER2-low indication; parallel pathway, not a TNBC-protocol trial
Modi S et al. N Engl J Med 2022;387:9–20 (PMID 35665782)
Atezolizumab (Tecentriq) + paclitaxel
IMpassion131 · NCT03125902
Roche/Genentech · N=651 · 1L
Metastatic TNBC, previously untreated (confirmatory)
vs Placebo + paclitaxel
PD-L1 IC ≥1% (SP142)
Confirmatory trial for SP142 IC≥1% population; did not confirm benefit.
5.7 vs 5.6 mo, HR 0.82 (PD-L1+, NS) 22.1 vs 28.3 mo (numerically favored placebo) None – failed primary endpoint
NEGATIVE – triggered withdrawal of atezolizumab TNBC indication
Miles D et al. Ann Oncol 2021;32:994–1004 (PMID 34219000)
Pembrolizumab (Keytruda) monotherapy
KEYNOTE-119 · NCT02555657
Merck (MSD) · N=622 · 2L/3L
Metastatic TNBC, previously treated (1–2 prior lines)
vs Chemo (physician's choice)
PD-L1 CPS (stratified ≥10 / ≥1 / ITT)
No mTNBC monotherapy indication resulted.
Not met No significant OS benefit (CPS≥10 HR 0.78, NS) None – failed primary endpoint
NEGATIVE – monotherapy not approved in mTNBC
Winer EP et al. Lancet Oncol 2021;22:499–511 (PMID 33676601)
2020-11-13 (accel); 2021-07-26 (full) Pembrolizumab (Keytruda) + chemotherapy
KEYNOTE-355 · NCT02819518
Merck (MSD) · N=847 (ITT) · 1L
Locally recurrent unresectable/metastatic TNBC, previously untreated
vs Placebo + chemo (nab-pac/pac/gem-carbo)
PD-L1 CPS ≥10
Label: PD-L1 (CPS ≥10) "as determined by an FDA-authorized test". CDx: PD-L1 IHC 22C3 pharmDx (Agilent/Dako).
9.7 vs 5.6 mo, HR 0.65 (CPS≥10) 23.0 vs 16.1 mo, HR 0.73 (CPS≥10, P=0.0185) Accelerated 2020-11-13; full 2021-07-26 (CPS≥10)
ACTIVE – 1L standard for PD-L1 CPS≥10
Cortes J et al. Lancet 2020;396:1817–28 (PMID 33278935); Cortes J et al. N Engl J Med 2022;387:217–26 (PMID 35857659)
2020-04-22 (accel); 2021-04-07 (full) Sacituzumab govitecan (Trodelvy)
ASCENT (confirmatory) · NCT02574455
Gilead (Immunomedics) · N=529 enrolled (468 without brain mets, primary analysis) · 2L+
Relapsed/refractory mTNBC, ≥2 prior therapies (≥1 for metastatic)
vs Chemo (eribulin/vinorelbine/capecitabine/gemcitabine)
None (Trop-2 ADC; not biomarker-selected)
No companion diagnostic; approval not biomarker-restricted.
5.6 vs 1.7 mo, HR 0.41 (P<0.001) 12.1 vs 6.7 mo, HR 0.48 (P<0.001) Accelerated 2020-04-22; full 2021-04-07 (2L+)
ACTIVE – 2L+ indication (one of three SG mTNBC settings)
Bardia A et al. N Engl J Med 2021;384:1529–41 (PMID 33882206)
2019-03-08 Atezolizumab (Tecentriq) + nab-paclitaxel
IMpassion130 · NCT02425891
Roche/Genentech · N=902 · 1L
Unresectable locally advanced/metastatic TNBC, previously untreated
vs Placebo + nab-paclitaxel
PD-L1 IC ≥1% (SP142)
Original label: PD-L1 tumor-infiltrating immune cells (IC) ≥1%. CDx: VENTANA PD-L1 (SP142) Assay. (Indication withdrawn 2021.)
7.5 vs 5.0 mo, HR 0.62 (PD-L1+) 25.0 vs 18.0 mo, HR 0.62 (PD-L1+, not formally tested*) Accelerated approval (PD-L1 IC≥1%)
WITHDRAWN (voluntary 2021-08) after IMpassion131 failed confirmation
Schmid P et al. N Engl J Med 2018;379:2108–21 (PMID 30345906); Adams S et al. Ann Oncol 2020;31:582–9 (PMID 32178964)
2018-10-16 Talazoparib (Talzenna)
EMBRACA · NCT01945775
Pfizer · N=431 · Advanced (≤3 prior chemo)
gBRCA1/2-mutated, HER2- locally advanced/metastatic breast cancer (~45% TNBC)
vs Chemo (physician's choice)
Germline BRCA1/2 mutation
Label: "Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA." CDx: BRACAnalysis CDx (Myriad).
8.6 vs 5.6 mo, HR 0.54 (P<0.001) 19.3 vs 19.5 mo, HR 0.85 (NS) Approved (gBRCAm HER2- MBC)
ACTIVE – genotype indication (gBRCAm), not TNBC-restricted
Litton JK et al. N Engl J Med 2018;379:753–63 (PMID 30110579)
2018-01-12 Olaparib (Lynparza)
OlympiAD · NCT02000622
AstraZeneca · N=302 · Metastatic (≤2 prior chemo)
gBRCA1/2-mutated, HER2- metastatic breast cancer (~50% TNBC)
vs Chemo (capecitabine/vinorelbine/eribulin)
Germline BRCA1/2 mutation
Label: "Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza." CDx: BRACAnalysis CDx (Myriad).
7.0 vs 4.2 mo, HR 0.58 (P<0.001) 19.3 vs 19.6 mo, HR 0.90 (NS) Approved (gBRCAm HER2- MBC)
ACTIVE – genotype indication (gBRCAm), not TNBC-restricted
Robson M et al. N Engl J Med 2017;377:523–33 (PMID 28578601)
HER2-low paradigm (DESTINY-Breast04, highlighted): Up to ~60% of traditional TNBC is reclassified as HER2-low (IHC 1+ or 2+/ISH-), routing those patients to trastuzumab deruxtecan — a HER2-directed ADC — rather than the Trop-2 ADC pathway. DESTINY-Breast04 was not a TNBC-protocol trial (primary endpoint was the HR-positive cohort); the HR-negative cohort (n=63, 11.3%) is the TNBC-relevant slice and its figures are exploratory subgroup analyses, shown as such.
2026 approvals: Dato-DXd TNBC 2026-05-22 (BLA761394 S3); sacituzumab govitecan 1L both settings 2026-06-24 (BLA761115 S63/64). Trials read out 2025; FDA actions landed 2026.
CDx vs clinical eligibility: PD-L1 CPS≥10 → 22C3 pharmDx "FDA-authorized test"; atezolizumab used SP142 IC≥1% (not interchangeable). BRCA → BRACAnalysis CDx. HER2-low → HER2 IHC "FDA-authorized test". Trop-2 ADC 1L single-agent → no CDx (clinical criterion "not candidates for PD-1/PD-L1 therapy").
Notes: ASCENT-03 randomized 558 (623 registered). ASCENT primary PFS in 468 without brain mets. TROPION-Breast02 OS mature/significant; ASCENT-03/04 OS immature. *IMpassion130 PD-L1+ OS not formally tested. Negative trials (KEYNOTE-119, IMpassion131) have no FDA application link.