Table 2 Current and upcoming clinical trials of immune checkpoint inhibitors in early triple negative breast cancer
Trial name: | Primary author: | Year: | Study design: | Line of therapy | Stage | # Patients: | Drug regimen | Results |
|---|---|---|---|---|---|---|---|---|
Pembrolizumab | ||||||||
NCT02622074 KEYNOTE-173 | Schmid | 2020 | Phase Ib | Neoadjuvant | cT1c, N1-N2; T2-T4c, N0-N2 | 60 | Nab-Paclitaxel + Pembrolizumab ± Carboplatin then AC | Overall pCR 60% (range 49%–71%) PD-L1 CPS associated with higher rate of pCR (p = 0.0127) sTILs associated with higher rate of of pCR (p = 0.0085) |
NCT01042379 I-SPY2 | Nanda | 2020 | Phase II | Neoadjuvant | cT2-4d, N0-3 | 29 | Arm A: Paclitaxel + Pembrolizumab then AC →  ± adjuvant Pembrolizumab Control: Paclitaxel then AC | pCR 60% (95% CI 44–75) vs 22% (13–30) |
NCT01042379 I-SPY2 | Liu | 2019 | Phase II | Neoadjuvant | T ≥ 2.5 cm; HER2 negative | 73 | Arm A: Paclitaxel + Pembrolizumab Control: Paclitaxel then AC | pCR 21% (95% CI 9–32) vs 20% (15–25) |
NCT01042379 I-SPY2 | Chien | 2021 | Phase II | Neoadjuvant | T ≥ 2.5 cm | 29 | Arm A: Paclitaxel + Pembrolizumab + SD-101 then AC + Pembrolizumab Control: Paclitaxel then AC | pCR 44% vs. 28% |
NCT00036488 KEYNOTE-522 | Schmid | 2020 | Phase III | Neoadjuvant + Adjuvant | cT1N1-2, cT2-4, N0-2 | 1174 | Arm A: Carboplatin + Paclitaxel + AC/EC + Pembrolizumab → adjuvant Pembrolizumab Arm B: Carboplatin + Paclitaxel + AC/EC + placebo → adjuvant placebo | pCR 64.8% (95% CI 59.9–69.9) vs 51.2% (44.1–58.3) PD-L1 CPS ≥ 1 pCR 68.9% vs 54.9% Risk of Recurrence HR = 0.63 (0.48–0.82) 5-year EFS 81.2% vs 72.2%; HR 0.63 (0.49–0.81) 5-year OS 86.6% (84.0–88.8) vs 81.7% (77.5–85.2) |
NCT03639948 NeoPACT | Sharma | 2022 | Phase II | Neoadjuvant | Stage I-III | 117 | Carboplatin + Docetaxel + Pembrolizumab | pCR 58% (95% CI: 48–67) 3-year EFS overall 86% EFS pCR subgroup: 98% EFS no pCR subgroup 68% |
NCT04373031 NeoIRX | Page | 2023 | Phase II | Neoadjuvant | Stage II/III | 12 | Arm A: Pembrolizumab + IRX-2 then AC/T + pembrolizumab Arm B: Pembrolizumab then AC/T + Pembrolizumab | pCR 83% vs. 33%; terminated early due to withdrawal of support for IRX-2 |
Atezolizumab | Â | Â | Â | Â | Â | Â | Â | Â |
NCT03197935 IMpassion031 | Mittendorf | 2020 | Phase III | Neoadjuvant | cT2-4, N0-3 | 333 | Arm A: Atezolizumab + AC + Nab-paclitaxel Arm B: placebo + AC + Nab-paclitaxel | ITT pCR 57.6% (95% CI 50–65) vs 41.1% (34–49), Difference 17% (6–27) PD-L1 ≥ 1 pCR 68.8% (57–79) vs 49.3% (38–61), Difference 20% (4–35) |
NCT002620280 NeoTRIPaPDL1/Michaelangelo | Gianni | 2022 | Phase III | Neoadjuvant | cT1N1-3; cT2-4d, N0-3 | 280 | Arm A: Atezolizumab + Carboplatin + Nab-paclitxel → adjuvant AC/EC Arm B: Carboplatin + Nab-paclitaxel → adjuvant AC/EC | pCR 48.6% vs. 44.4%, OR 1.18 (95% CI 0.74–1.89) PD-L1 + expression influenced rate of pCR, OR 2.08 (1.64–2.65) |
NCI10013 | Ademuyiwa | 2022 | Phase II | Neoadjuvant | cT2-4, N0-3 | 67 | Arm A: Atezolizumab + Carboplatin + Paclitxel Arm B: Carboplatin + Paclitxel | pCR 55.6 vs 18.8% |
NCT03498716 IMpassion030/ALEXANDRIA | Ignatiadis | 2023 | Phase III | Adjuvant | Stage II-III | 2199 | Arm A: Atezolizumab + ddAC + Paclitaxel Arm B: ddAC + Paclitaxel | iDFS HR 1.12 (95% CI 0.87—1.45) iDFS PD-L1 + 1.03 (0.75—1.42) |
Durvalumab | ||||||||
NCT02489448 | Foldi | 2021 | Phase I/II | Neoadjuvant | cT1-3, N0-3 | 59 | Durvalumab + AC + Nab-Paclitaxel | pCR 44% PD-L1 ≥ 1% pCR 55% |
NCT02685059 GeparNUEVO | Loibl | 2019 | Phase II | Neoadjuvant | cT2-4d, N0-3 | 174 | Arm A: Durvalumab window then Nab-Paclitaxel + Durvalumab then EC + Durvalumab Arm B: Placebo window then Nab-Paclitaxel + Placebo then EC + Placebo | pCR 53% vs. 44%, OR 1.45 (95% CI 0.80–2.63) 3-year iDFS 85.6% vs. 77.2%, HR 0.48 (0.24–0.97) 3-year DDFS 91.7% vs. 78.4%, HR 0.31 (0.13–0.74) 3-year OS 95.2% vs. 83.5%, HR 0.24 (0.08–0.72) |
NCT01042379 I-SPY2 | Pusztai | 2021 | Phase II | Neoadjuvant | Stage II-III | 21 | Arm A: Durvalumab + AC + Olaparib + Paclitaxel Arm B: AC + Paclitaxel | pCR 47% vs 27% |
Nivolumab | ||||||||
BCT1902 Neo-N | Loi | 2023 | Phase II | Neoadjuvant | cT1cN1; cT2-4, N0-1 | 110 | Arm A: Nivolumab Lead-In then Nivolumab + Carboplatin + Paclitaxel Arm B: Nivolumab + Carboplatin + Paclitaxel then Nivolumab alone | pCR 50.9% vs. 54.5% sTIL high vs low: 66.7% vs 45.7% PD-L1 positive vs negative: 70.6% vs 33.3% |
Dual Immunotherapy | Â | Â | Â | Â | Â | Â | Â | Â |
EudraCT: 2018-004188-30 BELLINI | Nederlof | 2022 | Phase II | Neoadjuvant | Stage I-III, TILs ≥ 5% | 31 | Arm A: Nivolumab then chemotherapy or surgery Arm B: Nivolumab + Ipilumumab then chemotherapy or surgery | Immune Activation = Doubling CD8+ T-cells or IFN-g seen in 58% of patients. Of 3 patients who went for surgery without neoadjuvant chemo, 1 pCR and 1 near-pCR |
BCT1702 CHARIOT | Loi | 2022 | phase II | Neoadjuvant + Adjuvant | Stage III with ≥ 15 mm RD or 10 mm RCB + one positive lymph node after AC × 4 | 34 | Ipilimumab + Nivolumab + Paclitaxel → adjuvant Nivolumab | pCR 24.2% PD-L1+ pCR 37.5% 3-year EFS 61.3% PD-L1+ 3-year EFS 100% 3-year OS 71.9% PD-L1+ 3-year OS 100% |
Selected Upcoming Clinical Trials | ||||||||
NCT05929768 SWOG2212/SCARLET |  |  | Phase III | Neoadjuvant | T2-4, N0, M0 or T1-3, N1-2, M0 with high TILs,PD-L1 | 2400 | Arm A: Carboplatin + Paclitaxel + AC + Pembrolizumab → adjuvant Pembrolizumab Arm B: Carboplatin + Docetaxel + Pembrolizumab | EFS |
NCT02954874 SWOG1418/NRGBR0006 |  |  | Phase III | Adjuvant |  ≥ 1 cm or N+ RCB | 1000 | Arm A: Pembrolizumab Arm B: Observation | iDFS in 1) all randomized patients and 2) PDL-1+ patients |
NCT02926196 A-BRAVE | Â | Â | Phase III | Adjuvant | RCB | 335 | Arm A: Avelumab Arm B: Observation | DFS |
NCT05812807 Optimice-pCR/A012103 | Â | Â | Phase III | Adjuvant | achieved pCR | 1295 | Arm A: Pembrolizumab Arm B: Observation | RFS |
NCT03281954 GeparDouze |  |  | Phase III | Neoadjuvant + Adjuvant | Stage II-III | 1550 | Arm A: Atezolizumab + Carboplatin + Paclitaxel then AC or EC → adjuvant Atezolizumab Arm B: Placebo + Carboplatin + Paclitaxel then AC/EC → adjuvant Placebo | pCR EFS |
NCT04427293 BRE-03 |  |  | Phase I | Neoadjuvant Window of Opportunity | Early-stage | 12 | Lenvatinib + Pembrolizumab | TILs present in biopsy |
NCT05973864 |  |  | Phase III | Adjuvant | Early-stage with RCB | 418 | Arm A: Capecitabine + Pembrolizumab Arm B: Pembrolizumab | iDFS |
NCT03036488 |  |  | Phase III | Neoadjuvant + Adjuvant | Locally Advanced | 1174 | Arm A: Pembrolizumab + Chemotherapy → adjuvant Pembrolizumab Arm B: Placebo + Chemotherapy → adjuvant Pembrolizumab | pCR |
NCT04335669 NordicTrip |  |  | Phase III | Neoadjuvant | Stage II-III | 920 | Arm A: EC + Pembrolizumab then Carboplatin + Paclitaxel + Pembrolizumab Arm B: EC + Capecitabine + Pembrolizumab then Carboplatin + Paclitaxel + Pembrolizumab | pCR |