Table 1.
Combinatorial immunotherapy approaches in HNSCC
| Combination immunotherapy | Mechanisms of action | Stage of clinical development | Study design | Setting |
| Nivolumab + ipilimumab | Anti-PD-1 + anti-CTLA-4 | Phase III (NCT02741570, Checkmate 651) | Nivolumab + ipilimumab vs EXTREME regimen | First-line R/M HNSCC |
| Durvalumab + tremelimumab | Anti-PD-L1 + anti-CTLA-4 | Phase III (NCT02551159, KESTREL) | Durvalumab vs durvalumab + tremelimumab vs EXTREME regimen | First-line R/M HNSCC |
| Durvalumab + tremelimumab | Anti-PD-L1 + anti-CTLA-4 | Phase III (NCT02369874, EAGLE) | Durvalumab vs durvalumab + tremelimumab vs EXTREME regimen | Platinum refractory R/M HNSCC |
| Durvalumab + tremelimumab | Anti-PD-L1 + anti-CTLA-4 | Phase II (NCT02319044, CONDOR) | Durvalumab vs tremelimumab vs durvalumab + tremelimumab | PD-L1-negative, platinum- refractory R/M HNSCC |
| Nivolumab + BMS-986016 | Anti-PD-1 + anti-LAG-3 | Phase I (NCT01968109) | Nivolumab + BMS-986016 vs BMS-986016 | Advanced solid tumours including HNSCC naive to immuno-oncology agents |
| Nivolumab + lirilumab | Anti-PD-1 + anti-KIR | Phase I (NCT01714739) | Nivolumab + lirilumab | Advanced solid tumours that have progressed to at least one standard regimen |
| Anti-PD-1 + TSR-022 | Anti-PD-1 + anti-TM-3 | Phase I (NCT02817633) | Expansion cohort Anti-PD-1 + TSR-022 vs TSR-022 |
Advanced refractory solid tumours |
| PDR001 + GWN323 | Anti-PD-1 + anti-GITR | Phase I (NCT02740270) | Expansion cohort PDR001+ GWN323 vs GWN323 |
Advanced solid tumours and lymphomas |
| Atezolizumab + MOXR0916 | Anti-PD-L1 + anti-OX40 | Phase I (NCT02410512) | Atezolizumab + MOXR0916 vs atezolizumab + MOXR0916 + bevacizumab | Advanced refractory solid tumours |
| Durvalumab + MEDI6383 | Anti-PD-L1 + anti-OX40 | Phase I (NCT02221960) | Durvalumab + MEDI6383 vs MEDI6383 | Advanced refractory solid tumours |
| Urelumab + cetuximab | Anti-4-1BB + anti-EGFR | Phase I (NCT02110082) | Urelumab + cetuximab | Advanced refractory HNSCC and colorectal cancer |
| Nivolumab + urelumab | Anti-PD-1 + anti-4-1BB | Phase I (NCT02253992) | Nivolumab + urelumab | Advanced refractory solid tumours/ lymphomas |
| PF-05082566 + PF-04518600 | Anti-4-1BB + anti-OX40 | Phase I (NCT02315066) | PF-05082566 + PF-04518600 vs PF-04518600 | Advanced solid tumours including HNSCC |
| Pembrolizumab + epacadostat | Anti-PD-1 + IDO inhibitor | Phase I/II (NCT02178722) | Pembrolizumab + epacadostat | Advanced solid tumours including HNSCC |
| Pembrolizumab + TVEC | Anti-PD-1 + oncolytic virus | Phase Ib/ III (NCT02626000, MASTERKEY232/KEYNOTE-034) |
Pembrolizumab + TVEC | R/M HNSCC not amenable to curative surgery/radiation |
| Pembrolizumab + p53MVA vaccine | Anti-PD-1 + vaccine | Phase I (NCT02432963) | Pembrolizumab + p53MVA vaccine | Advanced solid tumours including HNSCC that have progressed to at least one standard regimen |
| Durvalumab + ADXS11-001 | Anti-PD-1 + vaccine | Phase I (NCT02291055) | Durvalumab + ADXS11-001 vs ADXS11-001 vs durvalumab | Previously treated LA/metastatic HPV+ HNSCC or cervical cancer |
CTLA-4, cytotoxic T-lymphocyte-associated protein 4; EGFR, epidermal growth factor receptor; EXTREME regimen, platinum/5-fluorouracil + cetuximab; GITR, glucocorticoid-induced tumour necrosis factor receptor; HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; IDO, indoleamine 2,3-dioxygenase; KIR, killer-cell immunoglobulin-like receptor; LA, locally advanced; LAG-3, lymphocyte activation gene 3; PD-1, programmed cell death protein-1; PD-L1, programmed death ligand-1; p53MVA, modified vaccinia virus Ankara vaccine expressing p53; R/M, recurrent/metastatic; TIM-3, T-cell immunoglobulin and mucin domain 3; TVEC, talimogene laherparepvec.