Table 1

Combinatorial immunotherapy approaches in HNSCC

Combination immunotherapy Mechanisms of action Stage of clinical development Study design Setting
Nivolumab + ipilimumabAnti-PD-1 + anti-CTLA-4Phase III (NCT02741570, Checkmate 651)Nivolumab + ipilimumab vs EXTREME regimenFirst-line
Durvalumab + tremelimumabAnti-PD-L1 + anti-CTLA-4Phase III (NCT02551159, KESTREL)Durvalumab vs durvalumab + tremelimumab vs EXTREME regimenFirst-line
Durvalumab + tremelimumabAnti-PD-L1 + anti-CTLA-4Phase III (NCT02369874, EAGLE)Durvalumab vs durvalumab + tremelimumab vs EXTREME regimenPlatinum refractory
Durvalumab + tremelimumabAnti-PD-L1 + anti-CTLA-4Phase II (NCT02319044, CONDOR)Durvalumab vs tremelimumab vs durvalumab + tremelimumabPD-L1-negative, platinum- refractory R/M HNSCC
Nivolumab + BMS-986016Anti-PD-1 + anti-LAG-3Phase I (NCT01968109)Nivolumab + BMS-986016 vs BMS-986016Advanced solid tumours including HNSCC naive to immuno-oncology agents
Nivolumab + lirilumabAnti-PD-1 + anti-KIRPhase I (NCT01714739)Nivolumab + lirilumabAdvanced solid tumours that have progressed to at least one standard regimen
Anti-PD-1 + TSR-022Anti-PD-1 + anti-TM-3Phase I (NCT02817633)Expansion cohort
Anti-PD-1 + TSR-022 vs TSR-022
Advanced refractory solid tumours
PDR001 + GWN323Anti-PD-1 + anti-GITRPhase I (NCT02740270)Expansion cohort
PDR001+ GWN323 vs GWN323
Advanced solid tumours and lymphomas
Atezolizumab + MOXR0916Anti-PD-L1 + anti-OX40Phase I (NCT02410512)Atezolizumab + MOXR0916 vs atezolizumab + MOXR0916 + bevacizumabAdvanced refractory solid tumours
Durvalumab + MEDI6383Anti-PD-L1 + anti-OX40Phase I (NCT02221960)Durvalumab + MEDI6383 vs MEDI6383Advanced refractory solid tumours
Urelumab + cetuximabAnti-4-1BB + anti-EGFRPhase I (NCT02110082)Urelumab + cetuximabAdvanced refractory HNSCC and colorectal cancer
Nivolumab + urelumabAnti-PD-1 + anti-4-1BBPhase I (NCT02253992)Nivolumab + urelumabAdvanced refractory solid tumours/ lymphomas
PF-05082566 + PF-04518600Anti-4-1BB + anti-OX40Phase I (NCT02315066)PF-05082566 + PF-04518600 vs PF-04518600Advanced solid tumours including HNSCC
Pembrolizumab + epacadostatAnti-PD-1 + IDO inhibitorPhase I/II (NCT02178722)Pembrolizumab + epacadostatAdvanced solid tumours including HNSCC
Pembrolizumab + TVECAnti-PD-1 + oncolytic virusPhase Ib/ III
(NCT02626000, MASTERKEY232/KEYNOTE-034)
Pembrolizumab + TVECR/M HNSCC not amenable to curative surgery/radiation
Pembrolizumab + p53MVA vaccineAnti-PD-1 + vaccinePhase I (NCT02432963)Pembrolizumab + p53MVA vaccineAdvanced solid tumours including HNSCC that have progressed to at least one standard regimen
Durvalumab + ADXS11-001Anti-PD-1 + vaccinePhase I (NCT02291055)Durvalumab + ADXS11-001 vs ADXS11-001 vs durvalumabPreviously 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.