|
| Combinatorial approach | | Combination Therapy & Drug Used | Cancer Vaccine or Immunotherapy
Drug Used | Tumor Type & Reference |
|
| 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) |
|
| 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). |
|
| 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) |
|
