Table 1 Current and upcoming clinical trials of immune checkpoint inhibitors in advanced/metastatic triple negative breast cancer
Trial Name: | Primary Author | Year | Study Design | Line of Therapy | Setting | Biomarker | # Patients | Drug regimen | Results |
|---|---|---|---|---|---|---|---|---|---|
Pembrolizumab | |||||||||
NCT01848834 KEYNOTE-012 | Nanda | 2016 | Phase Ib | Heavily Pretreated | Metastatic | PD-L1 ≥ 1% | 32 | Pembrolizumab | ORR 18.5% (95% CI 6.3–38.1) DCR 25.9% (11.1–46.3) |
NCT02447003 KEYNOTE-086 | Adams | 2018 | Phase II | > First line | Metastatic | Any | 170 | Pembrolizumab | Overall ORR 5.3% (95% CI 2.7–9.9) PD-L1 + ORR 5.7% (2.4–12.2) Overall DCR 7.6% (4.4–12.7) PD-L1 + DCR 9.5% (5.1–16.8) |
NCT02447003 KEYNOTE-086 | Adams | 2018 | Phase II | First line | Metastatic | PD-L1 ≥ 1% | 84 | Pembrolizumab | ORR 21% (95% CI 13.9–31.4) DCR 23.8% (15.9–34.0) PFS 2.1 mo (2.0–2.2) OS 18.0 mo (12.9–23.0) |
NCT02628067 KEYNOTE-158 Cohort K | Maio | 2022 | Phase II |  > First line | Advanced/metastatic solid tumors, including breast | MSI-H or dMMR | 13 | Pembrolizuamb | ORR 30.8% (95% CI 25.8–36.2) PFS 3.5 mo (2.3–4.2) OS 20.1 (14.1–27.1) |
NCT02971761 | Yuan | 2020 | Phase II | Any | Metastatic | Androgen Receptor > 10% | 18 | Enobosarm + Pembrolizumab | RR 13% CBR 25% PFS 2.6 mo (95% CI 1.9–3.1) OS 25.5 mo (10.4-NE) |
NCT02513472 ENHANCE 1/KEYNOTE-150 | Tolaney | 2021 | Phase Ib/II | First to third line | Metastatic | Any | 167 | Eribulin + Pembrolizumab | Overall ORR 23.4% (95% CI 17.2–30.5) Overall PFS 4.1 mo (3.5–4.2) Overall OS 16.1 mo (13.3–18.5) First Line ORR 25.8% (15.8–38) First Line PFS 4.2 mo (3.5–5.5) First Line OS 17.4 mo (13.2–21.0) Second or Third Line ORR 21.8% (14.2–31.1) Second or Third Line PFS 4.1 mo (3.5–4.2) Second or Third Line OS 15.5 mo (12.5–18.7) |
NCT02657889 KEYNOTE-162/TOPACIO | Vinayak | 2019 | Phase II |  > First line | Advanced/metastatic | Any | 55 | Niraparib + Pembrolizumab | ORR 18% (90% CI 10–29); DCR 42% (31–54) BRCAmut ORR 47% (24–70), DCR 80% (56–94) BRCAwt ORR 11% (3–26), DCR 33% (19–51) PD-L1 CPS ≥ 1: ORR 32% (18–49), DCR 50% (33–67) |
NCT03106415 | Chumsri | 2023 | Phase I/II | ≤ 3 Lines, no prior PD-1 or PD-L1 therapies | Advanced/metastatic | Any | 22 | Binimetinib + Pembrolizumab | Safety: 3 patients with DLT ORR 29.4 (95% CI 10.3–55.9) with one CR and 4 PR CBR 35.3% (14.2–61.7) |
NCT02819518 KEYNOTE-355 | Cortes | 2020 | Phase III | First line | Metastatic | Any | 847 | Arm A: Nab-Paclitaxel/Paclitaxel/Gemcitabine-Carboplatin + Pembrolizumab Arm B: Nab-Paclitaxel/Paclitaxel/Gemcitabine-Carboplatin + Placebo | PFS CPS ≥ 10 9.7 vs. 5.6 mo, HR 0.66 (95% CI 0.50–0.88) PFS CPS ≥ 1 7.6 vs. 5.6 mo, HR 0.75 (0.62–0.91) PFS ITT 7.5 vs. 5.6 mo, HR 0.82 (0.70–0.98) OS CPS ≥ 10 23.0 vs. 16.1 mo, HR 0.73 (0.55–0.95) OS CPS ≥ 1 17.6 vs. 16.0 mo, HR 0.86 (0.72–1.04) OS ITT 17.2 vs. 15.5 mo, HR 0.89 (0.76–1.05) irAE 26.5% vs 6.4% |
NCT03044730 | Shah | 2020 | Phase II | Any | Metastatic | Any | 16 | Capecitabine + Pembrolizumab | ORR 13% CBR 15% PFS 4.0 mo (95% CI 1.9–12.7) |
NCT02555657 KEYNOTE-119 | Winer | 2021 | Phase III | > First line | Metastatic | Any | 622 | Arm A: Pembrolizaumab Arm B: Physician's choice of Capecitabine, Eribuin, Gemcitabine or Vinorelbine | ITT OS 9.9 vs. 10.8 mo, HR 0.97 (95% CI 0.82–1.15) CPS ≥ 10 OS 12.7 vs. 11.6 mo, HR 0.78 (0.57–1.06) CPS ≥ 1 OS 10.7 vs. 10.2 mo, HR 0.86 (0.69–1.06) ITT PFS 2.1 vs. 3.3 mo, HR 1.60 (1.33–1.92) CPS > 10 PFS 2.1 vs. 4.3 mo, HR 1.14 (0.82–1.59) CPS ≥ 1 PFS 2.1 vs. 3.1 mo, HR 1.35 (1.08–1.68) |
NCT03797326 LEAP-005 | Chung | 2020 | Phase Ib | > FIrst line | Advanced/metastatic | Any | 31 | Lenvatinib + Pembrolizumab | ORR 29% (95% CI 14–47) DCR 58% (38–76) 55% of patients had grade 3–5 TRAE with one death |
NCT03012230 | Kassi | 2023 | Phase I | Heavily pretreated | Metastatic | Any | 12 | Pembrolizumab + Ruxolitinib | 5 patients with grade 3 or higher AE; MTD not established 2 patients with stable disease lasting 6 mo |
NCT02411656 | Iwase | 2023 | Phase II | First Line maintenance | mTNBC or Inflammatory | Any | 43 | Pembrolizumab | 4-mo DCR 58.1% (95% CI 43.4–72.9) PFS 4.8 mo (3.0–7.1) |
NCT04191135 KEYLYNK-009 | Rugo | 2020 | Phase II | First Line maintenance | Metastatic | Any | 271 | Arm A: Olaparib + Pembrolizumab Arm B: Gemcitabine + Carboplatin + Pembrolizumab | PFS 5.5 vs. 5.6 mo, HR 0.98 (95% CI 0.72–1.33) OS 25.1 vs. 23.4 mo, HR 0.95 (0.64–1.40) PD-L1 ≥ 10% PFS 5.7 vs. 5.7 mo, HR 0.92 (0.59–1.43) PD-L1 ≥ 10% OS NE vs. NE BRCA + PFS 12.4 vs. 8.4 mo, HR 0.7 (0.33–1.48) BRCA + OS NE vs. 23.4 mo (17.3-NE) |
NCT02734290 | Page | 2023 | Phase Ib | First or second line | Metastatic | Any | 29 | Arm A: Paclitaxel + Pembrolizumab Arm B: Capecitbaine + Pembrolizumab | ORR 29% (95% CI 10–61) vs 43% (18–71) PFS 83 vs 155 days |
NCT02981303 IMPRIME 1 | O'Day | 2020 | Phase II | > First line | Metastatic | Any | 44 | Odetiglucan + Pembrolizumab | ORR 15.9% (95% CI 4.9–29.4) DCR 54.5% (40.1–68.3) 12 mo OS 57.6% (42.4–72.8) mOS 16.4 mo (11.1–23.9) |
Atezolizumab | |||||||||
NCT01633970 | Adams | 2019 | Phase Ib | Any | Metastatic | Any | 33 | Atezolizumab + Nab-Paclitaxel | ORR 39.4% (95% CI 22.9–57.9) DCR 51.5% (33.5–69.2) PFS 5.5 mo (5.1–7.7) OS 14.7 mo (10.1-NE) |
NCT02425891 IMpassion130 | Schmid | 2018 | Phase III | First line | Metastatic | PD-L1 positive | 902 | Arm A: Atezolizumab + Nab-Paclitaxel Arm B: Placebo + Nab-Paclitaxel | PFS 7.2 vs. 5.5 mo, HR 0.80 (95% CI 0.69–0.92) PD-L1 ≥ 1% PFS 7.5 vs. 5.0 mo, HR 0.62 (0.49–0.78) OS 21.3 vs. 17.6 mo, HR 0.84 (0.69–1.02) PD-L1 ≥ 1% OS 25.0 vs. 15.5 mo, HR 0.62 (0.45–0.86) irAE 57.3% vs 41.8% Grade 3 + irAEs 7.5% vs 4.3% |
NCT01375842 | Emens | 2019 | Phase I | Any | Metastatic | Any | 116 | Atezolizumab | First-Line ORR 24% (95% CI 8.2–47.2) First-Line OS 17.6 mo (10.2-NE)  ≥ Second-Line ORR 6% (2.4–13.4)  ≥ Second-Line OS 7.3 mo (6.1–10.8) |
NCT02322814 COLET | Brufsky | 2021 | Phase II | First line | Advanced/metastatic | Any | 153 | Cohort I: Arm A: Paclitaxel + Cobimetinib Arm B: Paclitaxel + Placebo Cohort II: Atezolizumab + Cobimetinib + Paclitaxel Cohort III: Atezolizumab + Cobimetinib + Nab-Paclitaxel | Cohort I PFS 5.5 vs 3.8 mo, HR 0.73 (95% CI 0.43–1.24) Cohort I Arm A ORR 38.3% (24.40–52.20) Cohort I Arm B ORR 20.9% (8.77–33.09) Cohort II ORR 34.4% (18.57–53.19) Cohort III ORR 29.0% (14.22–48.04) |
NCT02849496 | Fanucci | 2023 | Phase II | Any | Advanced / metastatic HER2 negative | BRCA1 or BRCA2 mutant | 78 | Arm A: Atezolizumab + Olaparib Arm B: Placebo + Olaparib | Overall PFS 7.67 (95% CI 5.6–10) vs. 7.0 mo (5.5–11.5) (p = 0.92) OS 26.5 (19.2-NE) vs 22.4 mo (16.6–31.3) (p = 0.3) |
NCT03125902 IMpassion131 | Miles | 2021 | Phase III | First line | Metastatic | Any | 651 | Arm A: Atezolizumab + Paclitaxel Arm B: Placebo + Paclitaxel | ITT PFS 5.7 vs. 5.6 mo, HR 0.86 (95% CI 0.70–1.05) ITT OS 19.2 vs. 22.8 mo, HR 1.12 (0.88–1.43) PD-L1 ≥ 1% PFS 6.0 vs. 5.7 mo, HR 0.82 (0.60–1.12) PD-L1 ≥ 1% OS 22.1 vs. 28.3 mo, HR 1.11 (0.76–1.64) irAE 62% vs 53% |
NCT03829501 | Patel | 2021 | Phase I/II | Heavily pretreated | Metastatic solid malignancy, including TNBC | Any | 69 | Atezolizumab + KY1044 | One CR, one PR |
NCT03371017 IMpassion132 | Dent | 2024 | Phase III | First relapse | Advanced, Early-Relapsing TNBC | Any | 354 | Arm A: Atezolizumab with Gemcitabine/Carboplatin or Capecitabine Arm B: Placebo with Gemcitabine/Carboplatin or Capecitabine | PD-L1 OS 12.1 vs. 11.2 mo, HR 0.93 (95% CI 0.73–1.20) OS 10.4 vs. 9.8 mo, HR 0.94 (0.76–1.18)* |
NCT03101280 COUPLET | Kristeleit | 2024 | Phase Ib/II | > First line | Metastatic | BRCA1 or BRCA2 mutant or BRCAwt/LOH high | 5 | Atezolizumab + Rucaparib | Safety: 2 of 5 patients experienced grade 3 or 4 AE ORR 40% (95% CI 5–85%), two PR |
NCT02708680 ENCORE-602 | O'Shaughnessy | 2020 | Phase II | Third line | Metastatic (TNBC or HR + /HER2 +) | Any | 81 | Arm A: Atezolizumab + Entinostat Arm B: Atezolizumab + Placebo | PFS 1.68 vs 1.51 mo, HR 0.89 (95% CI 0.53–1.48) |
NCT04408118 ATRACT1B | Gion | 2023 | Phase II | First line | Advanced/metastatic | Any | 100 | Atezolizumab + Bevacizumab + Paclitaxel | PFS 11.0 mo (95% CI 9.0–13.2) ORR 63% CBR 79% |
NCT04177108 IPATunity170 +  NCT03337724 IPATunity130 +  NCT03800836 CO40151 | Schmid | 2024 | Phase Ib-III | First line | Advanced/metastatic | Any | 317 | Atezolizumab + Ipatasertib + Paclitaxel/Nab-Paclitaxel +  | ORR 44%–63% mPFS 5.4–7.4 mo mDOR 5.6–11.1 mo mOS 15.7–28.3 mo |
Avelumab | |||||||||
NCT01772004 JAVELIN | Dirix | 2018 | Phase Ib | Heavily Pretreated | Metastatic | Any | 58 | Avelumab | Overall ORR 5.2% PD-L1 ≥ 1% ORR 22.2% |
Camrelizumab | |||||||||
NCT03805399 FUTURE Arm C | Liu | 2023 | Phase II | Heavily pretreated | Metastatic | Immunomodulatory | 46 | Camrelizumab + Nab-Paclitaxel | ORR 43.5% (95% CI 28.9–58.9) mPFS 4.6 mo (3.4–5.9) mOS 16.1 mo (11.7–20.5) mDOR 8.6 mo (1.2–19.7) |
NCT04129996 FUTURE-C-PLUS | Chen | 2022 | Phase II | First line | Advanced/metastatic | Immunomodulatory | 48 | Camrelizumab + Famitinib + Nab-Paclitaxel | ORR 81.3% (95% CI 70.2–92.3) mPFS 13.6 mo (8.4–18.8) mDOR 14.9 mo (NC–NC) |
NCT04395989 FUTURE-SUPER | Fan | 2024 | Phase II | First line | Advanced/metastatic | Immunomodulatory | 139 | Arm A: Camrelizumab + Famitinib + Nab-Paclitaxel Arm B: Nab-Paclitaxel | PFS 15.1 vs. 6.5 mo, HR 0.46 (95% CI 0.25–0.85) |
Durvalumab | |||||||||
NCT02734004 MEDIOLA | Domchek | 2020 | Phase I/II | > Third line | Metastatic HER2- (TNBC or HR +) | BRCA1 or BRCA2 mutant HER2-negative | 34 | Dulvalumab + Olaparib | ORR 63.3% (95% CI: 48.9–80.1) DCR at 12 weeks 80% (90% CI: 64.3–90.0) DCR at 28 weeks 50% (90% CI: 33.9–66.1) |
NCT02299999 SAFIR02-BREAST IMMUNO | Bachelot | 2021 | Phase II | First line maintenance | Metastatic | Any | 82 | Arm A: Durvalumab Arm B: Chemotherapy | mOS 14.0 vs 21.1 mo, HR 0.54 (95% CI 0.30–0.97) PD-L1 ≥ 1% mOS 27.3 vs. 12.1 mo, HR 0.37 (0.12–1.13) |
NCT03167619 DORA | Tan | 2024 | Phase II | First Line maintenance | Advanced/metastatic | Any | 45 | Arm A: Olaparib Arm B: Durvalumab + Olaparib | PFS 4.0 (95% CI 2.6–6.1) vs 6.1 mo (3.7–10.1) CBR 44% (23–66) vs 36% (17–59) |
Nivolumab | |||||||||
NCT02499367 TONIC | Voorwerk | 2019 | Phase I/II | Heavily pretreated | Metastatic | Any | 67 | Arm A: waiting period then Nivolumab Arm B: irradiation then Nivolumab Arm C: Cyclophosphamide then Nivolumab Arm D: Cisplatin then Nivolumab Arm E: Doxorubicin then Nivolumab | Overall ORR 20% Arm A ORR: 17% Arm B ORR: 8% Arm C ORR: 8% Arm D ORR: 23% Arm E ORR: 35% |
WJOG9917B NEWBEAT | Ozaki | 2022 | Phase II | First line | Metastatic | Any | 17 | Bevacizumab + Nivolumab + Paclitaxel | ORR 59% PFS 7.8 mo |
NCT02637531 MARIO-1 | Hong | 2023 | Phase I | Previously treated | Metastatic | Any | 29 | Part F: Eganelisib + Nivolumab | ORR 7%; one CR, one PR DCR 30% |
Toripalimab | |||||||||
NCT03777579 TORCHLIGHT | Jiang | 2024 | Phase III | First line | Advanced/metastatic | Any | 531 | Arm A: Nab-Paclitaxel + Toripalimab Arm B: Nab-Paclitaxel + Placebo | PD-L1 CPS ≥ 1 PFS 8.4 vs. 5.6 mo, HR 0.65 (95% CI 0.470–0.906) ITT PFS 8.4 vs. 6.9 mo, HR 0.77 (0.602–0.994) PD-L1 CPS ≥ 1 OS 32.8 vs. 19.5 mo, HR 0.62 (0.414–0.914) ITT OS 33.1 vs. 23.5 mo, HR 0.69 (0.513–0.932) |
LAG-3 modulation | |||||||||
NCT00349934 | Brignone | 2010 | Phase I/II | First line | Metastatic | Any | 30 | Eftilagimod + Paclitaxel | ORR 50% |
NCT02460224 | Lin | 2024 | Phase II | > First line | Advanced/Metastatic | Any | 56 | Arm A: Leramilimab + Spartzlizumab (q3W) Arm B: Leramilimab + Spartzlizumab (q4W) | ORR 9.5%; response only in PD-L1 positive |
Dual Immunotherap | |||||||||
|  | Santa Maria | 2018 | Pilot study | > First line | Metastatic | Any | 7 | Durvalumab + Tremelimumab | ORR 43% Hepatotoxicity major AE |
NCT02834013 DART/SWOG S1609 Cohort 36 | Adams | 2022 | Phase II | Any | Metaplastic | Any | 17 | Ipilumumab + Nivolumab | ORR 18% 3 responders all had ongoing response at 28 + mo. All responders had adrenal insufficiency |
NCT03789110 NUMBUS | Barrosa-Sousa | 2020 | Phase II | Any | Metastatic HER2- | TMB-High | 31 | Ipilumumab + Nivolumab | ORR 13.3% PFS 1.4 mo (95% CI 1.3–9.5) OS 8.8 mo (95% CI 4.2–NE) Exploratory: TMB ≥ 14 mut/Mb ORR 60% vs 9–14 ORR 4% (p = 0.01) No grade 4/5 toxicities |
NCT03650894 | Page | 2023 | Phase II | First or Second line | Metastatic HER2- | Any | 30 | Ipilumumab + Nivolumab + Bicalutamide | HR+ /Androgen Receptor Negative CBR 8% HR-/AR+ CBR 33% |
NCT02453620 | Roussos Torres | 2024 | Phase Ib | > First line | Metastatic | Any | 12 | Entinostat + Ipilumumab + Nivolumab | No DLT ORR 40% (95% CI 12.2–73.8) CBR 60% (95% CI 26.2–87.8) |
Selected Upcoming Clinical Trials | |||||||||
NCT04739670 BELLA |  |  | Phase II | First Relapse | Advanced, Early-Relapsing | PD-L1+  | 31 | Atezolizumab + Bevacizumab + Carboplatin + Gemcitabine | PFS |
NCT04148911 EL1SSAAR |  |  | Phase IIIb | First line | Advanced/metastatic | PD-L1+  | 184 | Atezolizumab + Nab-Paclitaxel | Safety |
NCT03961698 MARIO-3 |  |  | Phase II | First line | Advanced/metastatic | Any | 91 | Atezolizumab + Bevacizumab + Eganelisib +  Nab-paclitaxel | CRR |
NCT03915678 ADAGIR |  |  | Phase II | Heavily pretreated | Metastatic solid tumors, including TNBC | Any | 247 | Atezolizumab + BDB001 + stereotactic radiation | DCR |