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Combinatorial approach | | Combination Therapy & Drug Used | Cancer Vaccine or Immunotherapy Drug Used | Tumor Type & Reference |
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Strategies to increase tumor immunogenicity | Chemotherapy | Cyclophosphamide | Five peptide cancer vaccine | Phase I clinical trial in advanced solid tumors (NCT00676949) [12] |
Pembrolizumab | Advanced sarcomas and gastrointestinal tumors (NCT02406781) [13] |
Gemcitabine | GV1001 vaccine given with GMCSF adjuvant | In Phase 3 Telo-Vac clinical study in pancreatic cancer [14]. |
Anti-CD40 antibody APX005M or with nivolumab | Phase I and II clinical trial for pancreatic patients (NCT03214250) [15] |
Ipilimumab | Phase I clinical trial for Pancreatic Cancer (NCT01473940) |
Melphalan and Dactinomycin | Ipilimumab | Phase 2 trial in advanced melanoma (NCT01323517) |
Dacarbazine | Ipilimumab | Phase 3 clinical trial in advanced melanoma (NCT00324155) [16] |
Paclitaxel and Carboplatin | Ipilimumab | Phase 2 clinical trial for non–small cell lung cancer (NSCLC) (NCT00527735) and small-cell lung cancer (NCT 00527735) [17, 18] |
Paclitaxel, Carboplatin and Premetrexed | Pembrolizumab | Phase 2 clinical trial for lung cancer (NCT02039674) |
Paclitaxel, Carboplatin, gemcitabine | Nivolumab | Phase I clinical trial for Pancreatic, breast, NSCLC (NCT02309177) |
Radiotherapy | Stereotactic body radiation | Ipilimumab | Melanoma (NCT01970527), prostrate (NCT00323882) and lung cancer (NCT02239900). |
High dose IL-2 | Kidney and skin cancer (NCT01896271) [19] |
Pembrolizumab and nivolumab | Phase I and II clinical trials of radiation with in NSCLC (NCT3148327) [20] |
Nivolumab | Glioblastoma (NCT02617589), triple negative breast cancer (NCT02499367) |
Pembrolizumab | metastatic Head and neck squamous carcinoma (NCT03386357) |
Durvalumab and tremelimumab | Locally advanced Head and neck squamous carcinoma NCT03426657 |
Epigenetic Therapy | SGI-110 (DNMT inhibitor) | Ipilimumab | Melanoma (NCT02608437) |
Vorinostat (HDAC inhibitor) | Pembrolizumab | Renal cell carcinoma (NCT02619253) |
Entinostat (HDAC inhibitor) | Pembrolizumab | Melanoma and NSCLC (NCT02437136) |
Azacitidine (DNMT inhibitor) + entinostat | Nivolumab | NSCLC (NCT01928576) |
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Strategies to reverse tumor immunosuppression | Macrophage Targeted Therapy Blocking recruitment of macrophages | Carlumab (human anti-CCL2 IgG1κ mAb (CNTO 888) | | Prostrate cancer [21] and advanced cancer patients [22] |
PF-04136309 (CCL2-CCR2 axis inhibitor) | | PF-04136309 plus FOLFIRINOX show better treatment response in patients with locally advance PDAC (NCT01413022) |
Reduction of TAMs by depleting TAMs or its precursor | RG7155 (anti-CSF1R neutralizing antibodies) | | RG7155 demonstrated therapeutic efficacy in patients with diffuse-type giant cell tumor |
Plexiform Neurofibromas, Neurofibromatosis (NCT02390752) |
PLX3397 (pexidartinib) (CSF-1R inhibitor) | Urvalumab | Advanced Pancreatic and colorectal cancer (NCT02777710) |
Pembrolizumab | Melanoma and solid tumors (NCT02452424) |
BLZ945 (CSFIR inhibitor) | PDR001 (anti-PD1) | Phase I/II clinical trial in advanced solid tumors (NCT02829723) |
Trabectedin | | Phase III study showed trabectedin plus PLD improves overall survival than PLD alone in ovarian cancer Phase III trial in locally advanced or metastatic liposarcoma (NCT01692678) |
Reprogramming of macrophages into anti-tumor phenotype | IPI-549 | Pembrolizumab | Solid tumors (NCT02637531) |
RO7009789 (Agonist CD40 Ab) | Nab-paclitaxel and gemcitabine | Pancreatic adenocarcinoma (NCT02588443) |
Atezolizumab | Metastatic solid tumors (NCT02304393) |
TLR agonists | DV821 (TLR9 agonist) | Anti-PD1 ab | Phase I NSCLC NCT03326752 |
Poly-IC-LC (TLR3) | Pembrolizumab | Colon cancer (NCT02834052) |
MDSC Targeted therapy Reduction in accumulation of MDSCs | ATRA | Ipilimumab | Stage IV melanoma (NCT02403778) |
Bevacizumab, entinostat | Atezolizumab | Advanced renal cell carcinoma (NCT03024437) |
Blockade or recruitment of MDSCs | SX-682 | Pembrolizumab | Melanoma (NCT03161431) |
RTA-408 | Ipilimumab Nivolumab | Melanoma (NCT02259231) |
Treg targeted therapy | CCR4 inhibitor | Pembrolizumab | Phase 1 and 2 for solid tumors (NCT02178722) |
Epacadostat (IDO inhibitor) | Durvalumab | Advanced solid tumors (NCT02318277) |
Atezolizumab | NSCLC (NCT02298153) |
galunisertib (TGF beta inhibitor) | Durvalumab or nivolumab | Pancreatic cancer (NCT02423343). |
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Strategies to design and synthesize novel dual or triple inhibitory chemotypes that can block multiple pathways | | SF1126 | | Solid tumors (NCT00907205) |
| Recurrent or progressive SCCHN tumors (NCT02644122) |
| Neuroblastoma (NCT02337309) |
Nivolumab | Hepatocellular carcinoma (NCT03059147) |
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