Introduction
Crosstalk pathway in breast cancer
Targeted therapy
PARP inhibitors
CDK4/6 inhibitors
AKT Inhibitors
Angiogenesis inhibitors
FGFR inhibitors
S. no | Drugs (Year of regular approval) | Structures | Breast cancer subtypes | Conditions | Comments | References |
---|---|---|---|---|---|---|
PARP inhibitors | ||||||
1 | Olaparib (2018) | gBRCA-mutated HER2 − metastatic BC | Combination with chemotherapy in the adjuvant and neoadjuvant setting | Approval was based on the phase III OlympiAD trial (NCT02000622) | [129] | |
2 | Talazoparib (2018) | gBRCA-mutated HER2 − locally advanced or metastatic BC | - | Approval was based on the phase III EMBRACA trial (NCT01945775) | [52] | |
PI3K inhibitor | ||||||
3 | Alpelisib (2019) | HR + /HER2 − , PIK3CA-mutated, advanced or metastatic BC | Combination with an ER antagonist, fulvestrant | Approval was based on the phase III SOLAR-1 trial (NCT02437318) | [139] | |
mTOR inhibitor | ||||||
4 | Everolimus (2012) | Postmenopausal women with advanced HR + /HER2 − BC patients who have relapsed/ progressed following treatment with a non-steroidal aromatase inhibitor | Combination with a steroidal aromatase inhibitor, exemestane | Approval was based on the phase III BOLERO-2 trial (NCT00863655) | [140] | |
CDK4/6 inhibitors | ||||||
5 | Abemaciclib (2017, 2023) | Refractory HR + /HER2 − metastatic BC | Monotherapy | Approval was based on the phase II MONARCH-1 trial (NCT02747004) | ||
HR + /HER2 − advanced or metastatic BC | Combination with fulvestrant | Approval was based on the phase III MONARCH-2 trial (NCT02107703) | ||||
Postmenopausal BC | Combination with a nonsteroidal aromatase inhibitor, letrozole or anastrozole | Approval was based on the phase III MONARCH-3 trial (NCT02246621) | ||||
HR + /HER2 − , LN + adult patients with early breast cancer at high risk of recurrence | Combination with an adjuvant aromatase inhibitor, tamoxifen | Approval was based on the phase III monarchE trial (NCT03155997) | ||||
6 | Palbociclib (2017) | Postmenopausal ER + /HER2 − advanced BC | Combination with letrozole | Approval was based on the phase III PALOMA-2 trial (NCT01740427) | ||
HR + /HER2 − metastatic BC after endocrine failure | Combination with fulvestrant | Approval was based on the phase III PALOMA-3 trial (NCT01942135) | ||||
7 | Ribociclib (2017) | Postmenopausal advanced BC | Combination with letrozole | Approval was based on the phase III MONALEESA-2 trial (NCT01958021) | ||
Postmenopausal advanced BC | Combination with fulvestrant | Approval was based on the phase III MONALEESA-3 trial (NCT02422615) | ||||
Premenopausal HR + /HER2 − advanced BC | Combination with non-steroidal aromatase inhibitor and goserelin | Approval was based on the phase III MONALEESA-7 trial (NCT02278120) | ||||
Angiogenesis inhibitors | ||||||
8 | Lapatinib (2018) | Postmenopausal HR + , HER2 overexpressing advanced or metastatic BC | Combination with letrozole | Approval was based on the phase III trial (NCT00073528) | [145] | |
9 | Tucatinib (2020) | HER2 + advanced BC | Combination with trastuzumab and capecitabine | Approval was based on the phase III HER2CLIMB trial (NCT02614794) | [146] | |
10 | Neratinib (2020) | HER2 + metastatic BC | Combination with capecitabine | Approval was based on the phase III NALA trial (NCT01808573) | [147] |
Immunotherapy in breast cancer management
Immune checkpoint blockers
PD-1/PD-L1 blockers as immunotherapeutic agents
CTLA-4 blockers as immunotherapeutic agents
Other immune checkpoint inhibitors
S. no | Phases | Breast cancer subtypes | Immuno-therapeutic agents | Estimated participants | Co-treatment | Recruitment status | Identifiers |
---|---|---|---|---|---|---|---|
Anti-PD-1/PD-L1 therapy | |||||||
1 | I | Advanced TNBC | Pembrolizumab | 57 | ZEN003694, nab-paclitaxel | Recruiting | NCT05422794 |
2 | I | HLA-A2 + metastatic TNBC | Pembrolizumab | 20 | PVX-410 vaccine | Active, not recruiting | NCT03362060 |
3 | I | TNBC | Pembrolizumab | Not clearly mentioned | CPI-006 | Active, not recruiting | NCT03454451 |
4 | I | Early-Stage TNBC | Pembrolizumab | 12 | Lenvatinib | Recruiting | NCT04427293 |
5 | I | Metastatic TNBC | Pembrolizumab | 11 | TTAC-0001 | Active, not recruiting | NCT03720431 |
6 | I | TNBC | Pembrolizumab | 15 | Intraoperative radiation | Recruiting | NCT02977468 |
7 | I (early) | Metastatic TNBC | Pembrolizumab | 20 | Bortezomib plus cisplatin injections; bortezomib followed by pembro/cis | Recruiting | NCT04265872 |
8 | I | Advanced BC | Pembrolizumab | 150 | LY3475070 | Recruiting | NCT04148937 |
9 | I/II | Locally recurrent or metastatic TNBC | Pembrolizumab | 211 | Ladiratuzumab vedotin | Recruiting | NCT03310957 |
10 | II | HER-2 − metastatic TNBC | Pembrolizumab | 70 | Nab-paclitaxel | Active, not recruiting | NCT02752685 |
11 | II | TNBC | Pembrolizumab | 26 | Paclitaxel, cyclophosphamide, epirubicin | Recruiting | NCT05681728 |
12 | II | TNBC or HR + /HER2 − BC | Pembrolizumab | 23 | Olaparib | Recruiting | NCT05203445 |
13 | II | HR + localized inflammatory BC | Pembrolizumab | 37 | Hormonal therapy, radiation | Active, not recruiting | NCT02971748 |
14 | II | HER2 − inflammatory BC | Pembrolizumab | 81 | EC-paclitaxel | Recruiting | NCT03515798 |
15 | II | HER2 − BC and TNBC | Pembrolizumab | 47 | Decitabine followed by chemotherapy with cyclophosphamide, paclitaxel, carboplatin | Active, not recruiting | NCT02957968 |
16 | II | TNBC or HR + /HER2 − BC | Pembrolizumab | 56 | Olaparib, Radiation | Recruiting | NCT04683679 |
17 | II | Anthracycline- refractory TNBC | Pembrolizumab | 30 | Docetaxel, IL-12 gene therapy | Recruiting | NCT04095689 |
18 | II | Early-stage TNBC | Pembrolizumab | 29 | AE37 Peptide vaccine | Recruiting | NCT04427293 |
19 | II | TNBC | Pembrolizumab | 460 | Olaparib, carboplatin, gemcitabine | Active, not recruiting | NCT04191135 |
20 | II | Metastatic TNBC | Pembrolizumab | 40 | Cyclophosphamide | Active, not recruiting | NCT02768701 |
21 | II | Metastatic TNBC | Pembrolizumab | 30 | Nac-paclitaxel, carboplatin | Active, not recruiting | NCT03121352 |
22 | II | Inoperable locally recurrent or metastatic TNBC | Pembrolizumab | 65 | Tavokinogene telseplasmid, immunopulse, nab-paclitaxel | Recruiting | NCT03567720 |
23 | II | TNBC, PD-L1 − | Pembrolizumab | 110 | Sacituzumab govitecan | Recruiting | NCT04468061 |
24 | II | Metastatic TNBC | Pembrolizumab | 87 | Carboplatin, Gemcitabine | Recruiting | NCT02755272 |
25 | II | TNBC, BC | Pembrolizumab | 12 | IRX 2 | Active, not recruiting | NCT04373031 |
26 | II | TNBC, ER − , PR − , HER2 − , invasive BC | Pembrolizumab | 51 | Sacituzumab govitecan | Active, not recruiting | NCT04230109 |
27 | II | TNBC, HR + , HER2 − , LN + BC | Pembrolizumab | 120 | Radiation Therapy Boost, Paclitaxel, Carboplatin, Cyclophosphamide, Doxorubicin, Capecitabine | Recruiting | NCT04443348 |
28 | III | Inoperable locally recurrent or metastatic TNBC | Pembrolizumab | 882 | Nab-Paclitaxel, Paclitaxel, Gemcitabine, Carboplatin | Active, not recruiting | NCT02819518 |
29 | I/II | Metastatic TNBC | Nivolumab | 51 | Romidepsin, cisplatin | Active, not recruiting | NCT02393794 |
30 | I/II | Localized TNBC | Nivolumab | 50 | Paclitaxel, carboplatin, cabiralizumab | Active, not recruiting | NCT04331067 |
31 | I/II | HER2 + | Nivolumab | 390 | BDC-1001 | Recruiting | NCT04278144 |
32 | II | TNBC | Nivolumab | 45 | Capecitabine | Active, not recruiting | NCT03487666 |
33 | II | HR − , HER2 − , early stage/resectable BC | Nivolumab | 80 | Ipilimumab, core biopsy/cryoablation, breast surgery | Recruiting | NCT03546686 |
34 | II | Metastatic TNBC | Nivolumab | 52 | Cisplatin, doxorubicin (low-dose) | Recruiting | NCT04159818 |
35 | II | TNBC | Nivolumab | 84 | Radiation, doxorubicin (low-dose), cyclophosphamide, cisplatin | Active, not recruiting | NCT02499367 |
36 | II | Metastatic TNBC | Nivolumab | 78 | Carboplatin | Active, not recruiting | NCT03414684 |
37 | II | First-line metastatic TNBC | Nivolumab | 114 | Ipilimumab, capecitabine | Active, not recruiting | NCT03818685 |
38 | II | HR + , HER2 − or TNBC | Cemiplimab | 36 | Paclitaxel, carboplatin (not mandatory), doxorubicin, cyclophosphamide | Recruiting | NCT04243616 |
39 | II | Different BC subtypes | Cemiplimab | 5000 | AMG 386 with/without trastuzumab, AMG 479 plus metformin, AMG 386 plus trastuzumab, MK-2206 with/without trastuzumab, T-DM1 and pertuzumab, pertuzumab and trastuzumab, ganetespib ABT-888, neratinib, PLX3397, pembrolizumab (4 cycle), talazoparib plus irinotecan, patritumab and trastuzumab, pembrolizumab (8 cycle), SGN-LIV1A, durvalumab plus olaparib, SD-101 plus Pembrolizumab, tucatinib plus trastuzumab and pertuzumab, cemiplimab, cemiplimab plus REGN3767, trilaciclib with/without trastuzumab plus pertuzumab, SYD985, paclitaxel + dostarlimab encequidar + carboplatin with/ without trastuzumab, paclitaxel + encequidar + dostarlimab with/without trastuzumab, amcenestrant, amcenestrant plus abemaciclib, amcenestrant plus letrozole, ARX788, ARX788 plus cemiplimab, VV1 plus cemiplimab, datopotamab deruxtecan, datopotamab deruxtecan plus durvalumab, zanidatamab, lasofoxifene, Z-endoxifen | Recruiting | NCT01042379 |
40 | I | Different BC subtypes | Avelumab | 45 | Palbociclib | Recruiting | NCT04360941 |
41 | I/II | TNBC | Avelumab | 197 | Cyclophosphamide plus JX-594 dose escalation, cyclophosphamide plus JX-594, cyclophosphamide, avelumab plus JX-594 and cyclophosphamide | Recruiting | NCT02630368 |
42 | II | TNBC | Avelumab | 150 | PF-04518600, utomilumab, binimetinib, sacituzumab govitecan, doxorubicin, | Recruiting | NCT03971409 |
43 | II | BC, metastatic TNBC | Atezolizumab | 75 | Doxorubicin plus cyclophosphamide, placebo for atezolizumab | Active, not recruiting | NCT03164993 |
44 | II | BC, metastatic TNBC | Atezolizumab | 23 | Talazoparib, radiation | Active, not recruiting | NCT04690855 |
45 | II | TNBC | Atezolizumab | 458 | Carboplatin, paclitaxel, epirubicin, cyclophosphamide, surgery | Active, not recruiting | NCT04770272 |
46 | II | TNBC and IV, HER2 − and invasive BC | Atezolizumab | 106 | Carboplatin | Active, not recruiting | NCT03206203 |
47 | II | TNBC, invasive BC, breast adenocarcinoma | Atezolizumab | 37 | Nab-Paclitaxel | Active, not recruiting | NCT02530489 |
48 | II | Advanced or metastatic TNBC | Atezolizumab | 100 | Paclitaxel, bevacizumab | NCT04408118 | |
49 | II | TNBC | Atezolizumab | 284 | Capecitabine or capecitabine (monotherapy) | Recruiting | NCT03756298 |
50 | II | TNBC and Brain Metastasis | Atezolizumab | 45 | Stereotactic radiosurgery | Active, not recruiting | NCT03483012 |
51 | II | Advanced TNBC | Atezolizumab | 52 | Stereotactic radiosurgery | Active, not recruiting | NCT03464942 |
52 | III | Inoperable locally advanced or metastatic TNBC | Atezolizumab | 180 | Nab-paclitaxel | Active, not recruiting | NCT04148911 |
53 | III | TNBC | Atezolizumab | 1550 | Atezolizumab, paclitaxel (neoadjuvant chemotherapy) carboplatin, doxorubicin, cyclophosphamide, epirubicin, (adjuvant continuation), surgery | Active, not recruiting | NCT03281954 |
54 | III | TNBC | Atezolizumab | 2300 | Paclitaxel, doxorubicin/epirubicin, cyclophosphamide | Active, not recruiting | NCT03498716 |
55 | III | Recurrent, inoperable locally advanced or metastatic TNBC | Atezolizumab | 572 | Gemcitabine, capecitabine, carboplatin | Recruiting | NCT03371017 |
56 | III | TNBC | Atezolizumab | 278 | Carboplatin, nab-paclitaxel, anthracycline chemotherapeutic drug, cyclophosphamide or fluorouracil, epirubicin and cyclophosphamide | Active, not recruiting | NCT02620280 |
57 | I | TNBC | Durvalumab | 18 | Neoantigen DNA vaccine | Active, not recruiting | NCT03199040 |
58 | I | Stage 2/3 TNBC | Durvalumab | 22 | PVX-410, Hiltonol | Active, not recruiting | NCT02826434 |
59 | I/II | TNBC | Durvalumab | 171 | Paclitaxel, carboplatin, oleclumab | Active, not recruiting | NCT02489448 |
60 | I/II | Locally advanced luminal B HER2 − | Durvalumab | 57 | Paclitaxel, epirubicin, cyclophosphamide | Active, not recruiting | NCT03356860 |
61 | I/II | TNBC | Durvalumab | 200 | Capivasertib, oleclumab paclitaxel, trastuzumab deruxtecan, datopotamab deruxtecan | Active, not recruiting | NCT03742102 |
62 | II | Advanced and metastatic TNBC | Durvalumab | 28 | CFI-400945 | Active, not recruiting | NCT04176848 |
63 | II | Stage 4 BC AJCC v8, TNBC | Durvalumab | 28 | Olaparib | Recruiting | NCT03801369 |
64 | II | Stage 4 BC AJCC v8, invasive TNBC | Durvalumab | 70 | Carboplatin, gemcitabine hydrochloride, nab-paclitaxel, peptide vaccine, poly ICLC, tremelimumab | Recruiting | NCT03606967 |
65 | II | Breast neoplasm | Durvalumab | 81 | AZD6738, olaparib | Recruiting | NCT03740893 |
66 | II | Different BC subtypes | Durvalumab | 5000 | Olaparib | Recruiting | NCT01042379 |
Anti-CTLA-4 therapy | |||||||
67 | II | Stage 4 BC AJCC v8, invasive BC, metastatic TNBC | Tremelimumab | 70 | Carboplatin, gemcitabine hydrochloride, nab-paclitaxel, peptide vaccine, poly ICLC, durvalumab | Recruiting | NCT03606967 |
68 | I | Different types of cancers including ER − , PR − , HER2 − BC | Ipilimumab | 234 | XmAb®23,104 | Recruiting | NCT03752398 |
69 | I/II | Advanced solid tumors including BC | Ipilimumab | 100 | Pembrolizumab plus durvalumab | Recruiting | NCT05187338 |
70 | I/II | Advanced solid tumors including metastatic BC | Ipilimumab | 914 | ONC-392 | Recruiting | NCT04140526 |
71 | II | HR − , HER2 − , early stage/resectable BC | Ipilimumab | 80 | Nivolumab, core biopsy/cryoablation, breast surgery | Recruiting | NCT03546686 |
72 | II | HER2 − metastatic or inoperable BC | Ipilimumab | 138 | Nivolumab, bicalutamide | Recruiting | NCT03650894 |
73 | I | Advanced solid tumors including TNBC | SI-B003 (a CTLA-4/PD-1 bispecific antibody) | 159 | - | Recruiting | NCT04606472 |
74 | I/II | Inoperable locally advanced or metastatic cancers including BC | JK08 (CTLA-4 targeting IL-15 antibody fusion protein) | 149 | - | Recruiting | NCT05620134 |
Anticancer vaccines
HER2 targeting breast cancer vaccines
Non-HER2 targeting breast cancer vaccines
Adoptive T-cell therapy
S. no | Phases | Breast cancer subtypes | Precondition | Immuno-therapeutic agents | Estimated participants | Co-adjuvants | Recruitment status | Identifiers |
---|---|---|---|---|---|---|---|---|
Tumor-infiltrating lymphocyte (TIL) therapy | ||||||||
1 | II | Metastatic TNBC | Yes | TIL LN-145 | 6 | - | Active, not recruiting | NCT04111510 |
2 | II | Metastatic cancers including BC (mixed) | Yes | Young TIL | 332 | Anti-PD1 | Recruiting | NCT01174121 |
T-cell receptor (TCR) therapy | ||||||||
3 | II | BC (mixed) | Yes | Sleeping Beauty Transposed PBL | - | Recruiting | NCT04102436 | |
4 | II | Metastatic cancers including BC (mixed) | Yes | Autologous TCR-Transduced PBL | 270 | Anti-PD1 | Recruiting | NCT03412877 |
CAR-T cell therapy | ||||||||
5 | I | HER2 + solid tumors including BC | Yes | CCT303-406 CAR-modified autologous T cells (CCT303-406) | 15 | - | Recruiting | NCT04511871 |
6 | I | Metastatic BC (mixed) | No | huMNC2-CAR44 T cells and huMNC2-CAR44 T cells @ RP2D | 69 | - | Recruiting | NCT04020575 |
7 | I | Brain or Leptomeningeal metastases from HER2 + cancer including BC | No | HER2-CAR T cells | 39 | - | Recruiting | NCT03696030 |
8 | I | HER2 + cancer including BC | No | HER2-CAR T cells | 45 | CAdVEC oncolytic virus | Recruiting | NCT03740256 |
9 | I | Refractory neuroblastoma and other GD2 + cancers including BC | Yes | C7R-GD2.CAR-T cells | 94 | - | Recruiting | NCT03635632 |
10 | I | Advanced solid tumors including recurrant BC | No | EpCAM CAR-T cells | 30 | - | Recruiting | NCT02915445 |
11 | I | BC (mixed), metastatic HER2-negative BC | Yes | Mesothelin-targeted T cells | 186 | - | Active, not recruiting | NCT02792114 |
12 | I/II | BC (mixed) | No | Multi-4SCAR-T cells | 100 | - | Recruiting | NCT04430595 |
13 | I/II | Relapsed/refractory CEA + cancer including BC | No | CEA CAR-T cells | 40 | - | Recruiting | NCT04348643 |
14 | I/II | CD44v6 + cancer including BC | No | CD44v6-specific CAR-T cells | 100 | - | Recruiting | NCT04427449 |
15 | I/II | CD70 expressing cancers including BC | Yes | Anti-hCD70 CAR-transduced PBL | 124 | - | Recruiting | NCT02830724 |
16 | I/II | Different types of cancer including BC (mixed) | Yes | iCasp9M28z T cell infusions | 113 | Anti-PD1 | Active, not recruiting | NCT02414269 |
Dendritic cell (DC) therapy | ||||||||
17 | I | HER2 + BC | No | HER-2 pulsed DC vaccine | 15 | - | Active, not recruiting | NCT02063724 |
18 | I | HER2 + BC | No | HER-2 pulsed DC vaccine | 7 | - | Active, not recruiting | NCT02061423 |
19 | I | HER2 + BC (mixed) | No | DC vaccine (DC1) | 31 | - | Active, not recruiting | NCT03387553 |
20 | II | HER2 + BC (mixed) | No | DC vaccine (DC1) | 119 | - | Active, not recruiting | NCT03384914 |
21 | II | BC (mixed) | No | DC-CIK immunotherapy | 400 | CIK | Active, not recruiting | NCT02491697 |
22 | II | Asymptomatic brain metastasis from TNBC or HER2 + BC | No | Anti-HER2/HER3 DC vaccine | 23 | Anti-PD1, IFNa2b | Recruiting | NCT04348747 |
Natural killer (NK) cell therapy | ||||||||
23 | I | Advanced or metastatic HER2-expressing solid tumors including BC | Yes | ACE1702 | 36 | - | Recruiting | NCT04319757 |