Table 1.
Immunotherapy clinical trials in the United States currently open and enrolling patients.
| Drug Category and Name | Mechanism | Combination | Status | Clinical Trial ID | Target Population |
|---|---|---|---|---|---|
| Checkpoint/ co-stimulatory studies | |||||
| Nivolumab | PD1 blocking mAb | single agent | Phase III | NCT02105636 | Recurrent or metastatic HNSCC |
| Nivolumab | PD1 blocking mAb with CD27 agonist mAb | with Varlilumab | Phase I/II | NCT02335918 | Advanced solid tumors |
| Nivolumab | PD1 blocking mAb with IDO1 inhibitor | with INCB24360 | Phase I/II | NCT02327078 | Advanced solid tumors |
| Nivolumab | PD1 blocking mAb with CSF1R blocking mAb | with PLX3397 | Phase I | NCT02526017 | Advanced solid tumors |
| Nivolumab | PD1 blocking mAb | single agent | Phase I/II | NCT02488759 | Advanced and metastatic HPC-associated HNSCC |
| Pembrolizumab | PD1 blocking mAb with Bruton’s TKI | with ACP-196 | Phase II | NCT02454179 | Advanced HNSCC |
| Pembrolizumab | Head to head comparison | vs. standard treatment (docetaxel/methotrexate/cetixumab) | Phase III | NCT02252042 | Recurrent or metastatic HNSCC |
| Pembrolizumab | Head to head comparison | Pembro+standard treament vs. cetiximab+standard treatment | Phase III | NCT02358031 | Recurrent or metastatic HNSCC |
| Pembrolizumab | PD1 blocking mAb | single agent | Phase II | NCT02255097 | Recurrent or metastatic HNSCC after CDDP/cetixumab failure |
| Pembrolizumab | PD1 blocking mAb with IDO1 inhibitor | with INCB024360 | Phase I/II | NCT02178722 | Advanced or recurrent solid tumors |
| Pembrolizumab | PD1 blocking mAb with CSF1R blocking mAb | with PLX3397 | Phase I/II | NCT02452424 | Advanced solid tumors |
| Pembrolizumab | PD1 blocking mAb | single agent, window-of-opportunity trial before surgery | Phase II | NCT02296684 | Advanced but resectable HNSCC |
| Pembrolizumab | PD1 blocking mAb with B7-H3 blocking mAb | with MGA271 | Phase I | NCT02475213 | B7-H3+ advanced HNSCC |
| PF-05082566 | 41BB agonist mAb with PD1 blocking mAb | with Pembrolizumab | Phase I | NCT02179918 | Advanced solid tumors |
| Urelumab | 41BB agonist mAb with EGFR targeting mAb | with cetuximab | Phase I | NCT02110082 | Advanced/metastatic HNSCC |
| MEDI4736 | PD-L1 blocking mAb with CTLA4 blocking mAb | with or without tremelimumab | Phase III | NCT02369874 | Recurrent or metastatic HNSCC |
| MEDI4736 | PD-L1 blocking mAb with STAT3 inhibitor or CXCR2 blocking mAb | with AZD9150 or AZD5069 | Phase I/II | NCT02499328 | Metastatic HNSCC |
| MEDI4736 | PD-L1 blocking mAb | single agent | Phase II | NCT02207530 | Recurrent or metastatic HNSCC |
| MEDI4736 | PD-L1 blocking mAb with HPV E7 expressing Listeria vector | with ADXS 11-001 | Phase I/II | NCT02291055 | Recurrent or metastatic HPV-associated HNSCC |
| MEDI4736 | PD-L1 blocking mAb with CCR4 blocking mAb | with mogamulizumab | Phase I | NCT02301130 | Advanced solid tumors |
| Tremelimumab | CTLA4 blocking mAb with CCR4 blocking mAb | with mogamulizumab | Phase I | NCT02301130 | Advanced solid tumors |
| Ipilimumab | CTLA4 blocking mAb | with cetiximab and XRT | Phase I | NCT01935921 | Advanced HNSCC |
| Ipilimumab | CTLA4 blocking mAb with B7-H3 blocking mAb | with MGA271 | Phase I | NCT02381314 | B7-H3+ advanced HNSCC |
| PF04518600 | OX40 agonist mAb | single agent | Phase I | NCT02315066 | Recurrent or metastatic HNSCC |
| MDSC targeting trials | |||||
| Tadalafil | PDE5 inhibitor | single agent | Phase II | NCT01697800 | All stage HNSCC |
| Therapeutic Vaccines | |||||
| VGX-3100 and INO-9012 | HPV DNA vaccine | single agent, delivered via IM electroporation, both surgery and CRT arms | Phase I/II | NCT02163057 | HPV-associated HNSCC |
| ADXS 11-001 | HPV E7 expressing Listeria vector | with or without αPD-L1 mAb (MEDI4736) | Phase I/II | NCT02291055 | HPV-associated HNSCC |
| ADXS 11-001 | HPV E7 expressing Listeria vector | single agent, window-of-opportunity trial before surgery | Phase II | NCT02002182 | Stage II-IV resectable HPV-associated OPSCC |
| CDDP plus VICORYX-2 | p16 peptide antigen | with or without Montanide® ISA-51 VG (adjuvant) | Phase I | NCT02526316 | HPV-associated HNSCC (p16+) |
| AlloVax | Whole tumor cell lysate vaccine | with AlloStim adjuvant | Phase I/II | NCT01998542 | Metastatic or recurrent HNSCC |
| Adoptive T Cell Transfer | |||||
| Adoptive cell transfer | Ex-vivo TIL expansion with adoptive transfer | combined with lymphodepletion | Phase II | NCT01585428 | Metastatic HPV-associated OPSCC |
| Adoptive cell transfer | Ex-vivo TIL expansion after genetic modification with adoptive transfer | combined with lymphodepletion, viral insertion of a HPV-specific TCR | Phase I/II | NCT02280811 | All HPV-associated cancer |
| Cetuximab-based trials | |||||
| Cetixumab | EGFR targeting mAb with standard treatments | with XRT and paclitaxel-poliglumex | Phase I/II | NCT00660218 | HPV-negative advanced HNSCC |
| Cetixumab | EGFR targeting mAb with XRT | XRT | Phase II | NCT00904345 | Advanced HNSCC |
| Cetixumab | EGFR targeting mAb with αCTLA4 mAb with XRT | Ipilumimab and XRT | Phase I | NCT01935921 | Advanced HNSCC |
| Cetixumab | Head to head comparison | cetixumab plus XRT vs. CDDP plus XRT | Phase III | NCT01855451 | HPV-associated HNSCC |
| Cetixumab | EGFR targeting mAb with cyclin D inhibitor | with PD0332991 | Phase I/II | NCT02101034 | Incurable HNSCC |
| Cetixumab | Head to head comparison | cetuximab vs. MEHD7945A | Phase II | NCT01577173 | Metastatic or recurrent HNSCC |
| Cetixumab | EGFR targeting mAb with TLR8 agonist | with VTX-2337, window-of-opportunity trial before surgery | Phase I | NCT02124850 | resectable HNSCC |
| Cetixumab | EGFR targeting mAb with TLR8 agonist and chemotherapy | with VTX-2337 and CDDP+5-FU | Phase II | NCT01836029 | Recurrent or metastatic HNSCC |
PD1, programmed cell death 1; HNSCC, head and neck squamous cell carcinoma; mAb, monoclonal antibody; IDO1, indoleamine 2,3-dioxygenase 1; CSF1R, colony stimulating factor receptor 1; TKI, tyrosine kinase inhibitor; EGFR, epidermal grwoth factor receptor; CTLA4, cytotoxic T-lymphocyte-associated protein 4; STAT3, signal transducer and activator of transcription 3; PDE5, phosphodiesterase 5; HPV, human papillomavirus; TIL, tumor infiltrating lymphocyte; TCR, T-cell receptor; CDDP, cisplatin; OPSCC, oropharyngeal squamous cell carcinoma; XRT, radiation therapy; TLR8. toll-like receptor 8; 5-FU, 5-flourouracil.