Table 1.
Ongoing clinical trials targeting the TME ± immunotherapy in HNSCC.
| Trial NCT/Name | N of Pts | Phase | Stage/Eligibility | Treatment | Target | Primary Endpoint |
|---|---|---|---|---|---|---|
| TAMs | ||||||
| NCT02323191 | 221 | I | Advanced solid tumors | Emactuzumab + Atezolizumab | CSF1R PD-L1 |
% of pts with DLTs MTD of emactuzumab % of pts with AEs |
| NCT02526017 | 295 | I | Advanced Solid tumors (including a HNSCC cohort) | Cabiralizumab + Nivolumab | CSF1R PD-1 |
Safety RD of cabiralizumab ORR |
| NCT03906526 | 72 | I | Untreated, resectable HNSCC | Motolimod + Nivolumab, motlimod monotherapy, nivolumab monotherapy | TLR8 PD-1 |
Number of CD8+ T cells pre-treatment and post-surgery |
| NCT02304393 | 140 | Ib | Advanced solid tumors | Selicrelumab + Atezolizumab | CD40 PD-L1 |
Safety, MTD, DLTs, PFS, ORR, OS |
| NCT03329950 | 260 | I | Advanced Solid tumors (including a HNSCC cohort) | CDX-1140, CDX-1140+ pembrolizumab or chemotherapy or CDX-301 | CD40 PD-1 |
Safety and tolerability |
| NCT03795610 | IΙ | Resectable HNSCC | IPI-549 | PI3Kγ | PI3Kγ changes | |
| CAFs | ||||||
| NCT03386721 | 322 | II | Advanced HNSCC, NSCLC, squamous esophageal and cervical cancers | RO6874281 + atezolizumab | FAP PD-L1 |
ORR |
| NCT03195699 | 30 | I | Advanced Solid tumors (including a HNSCC cohort) | C118-9 | STAT3 | MTD and pharmacokinetics |
| NCT03153982 | 45 | II | Resectable HNSCC | Ruxolitinib | JAK2 | Changes in tumor size |
| Tregs | ||||||
| NCT04504669 | 123 | I | Advanced Solid tumors (including a HNSCC cohort) | AZD8701 ± durvalumab | FOXP3 PD-L1 |
MTD, AEs, ORR |
| NCT02946671 | 16 | I | Resectable cancers, including oral cancer | Mogamulizumab+ Nivolumab | CCR4 PD-1 |
AEs, FOXP3 (+) tumors |
| NCT02301130 | 64 | I | Advanced solid tumors | Mogamulizumab + Durvalumab or Mogamulizumab + Tremelimumab |
CCR4 PD-L1 CTLA-4 |
Safety |
| NCT02705105 | 114 | I/II | Advanced solid tumors | Mogamulizumab + Nivolumab | CCR4 PD-1 |
MTD, DLT |
| NCT02274155 | 17 | Ib | Resectable stage III-IV HNSCC | MEDI6469 | OX-40 | Safety and feasibility of surgical resection |
| NCT03336606 | 35 | Ib | Advanced resectable HNSCC, Stage IIIB/IIIC melaonoma | MEDI0562 | OX-40 | Immune activation |
| NCT02221960 | 39 | I | Recurrent/Metastatic solid tumors | MEDI6383 | OX-40 PD-L1 |
Safety |
| NCT04198766 | 150 | I | Advanced Solid tumors (including a HNSCC cohort) | INBRX 106 +/- permbrolizumab | OX-40 PD-1 |
Safety, MTD |
| NCT04465487 | 75 | I | Advanced Solid tumors (including a HNSCC cohort) | REGN6569 + Cemiplimab | GITR PD-1 |
Safety, DLTs, ORR, percentage change in GITR/Treg density |
| NCT04262388 | 120 | II | Recurrent/Metastatic HNSCC, NSCLC and pancreatic cancer | Oleclumab + durvalumab | CD73 PD-L1 |
mRNA-seq based assay of blood samples, toxicity, ORR, DCR, DoR |
| MDSCs | ||||||
| NCT03358472 | 89 | III | R/M HNSCC | Epacadostat + Pembrolizumab vs Pembrolizumab vs EXTREME regimen | IDO1 PD-1 |
ORR |
| NCT03854032 | 48 | II | Stage II-IV HNSCC | BMS-986205 + nivolumab | IDO1 PD-1 |
ORR |
| NCT01697800 | 40 | II | Resectable or locally advanced HNSCC | Tadalafil vs placebo | PDE5 | Change in immune response |
| NCT02544880 | 16 | I/II | Resectable recurrent or second primary HNSCC | Tadalafil + anti-MUC1 vaccine + anti-influenza vaccine | PDE5 | Safety Tumor-specific immune response |
| Angiogenesis | ||||||
| NCT03818061 | 110 | II | R/M HNSCC | Bevacizumab +Atezolizumab | VEGF PD-L1 |
ORR |
| NCT03650764 | 42 | I/II | R/M HNSCC | Ramucirumab + Pembrolizumab | VEGFR2 PD-1 |
RD of Ramurcirumab ORR |
| NCT04199104 | 500 | III | PD-L1 (+) R/M HNSCC | Lenvatinib + Pembrolizumab vs Pembrolizumab | VEGFR1,2,3 PD-1 |
ORR, PFS, OS |
| T cells | ||||||
| NCT04128696 | 600 | II/III | PD-L1 (+) R/M HNSCC | GSK3359609 + Pembrolizumab vs. Pembrolizumab | ICOS PD-1 |
OS and PFS in PD-L1 CPS ≥ 1, OS in PD-L1 CPS ≥ 20 |
| NCT04428333 | 640 | II/III | R/ HNSCC | GSK3359609 + Pembrolizumab+ 5-FU/platinum vs. Pembrolizumab + 5-FU/platinum |
ICOS PD-L1 |
OS and PFS in total population, PFS in PD-L1 CPS ≥ 1 |
AE = Adverse Event, CAFs = Cancer Associated Fibroblasts, CCR4 = C-C Motif Chemokine Receptor 4,CD73 = Cluster of Differentiation 73, CD40 = Cluster of differentiation 40, CSF1R = Colony stimulating factor, receptor, CTLA-4 = Cytotoxic T Lymphocyte-Associated protein 4, DCR = Disease Control Rate, DLT = Dose Limiting Toxicity, DoR = Duration of Response, FAP = Fibroblast Activation Protein, FOXP3 = Forkhead box P3, GITR = Glucocorticoid-Induced TNFR-related protein, HNSCC = Head and Neck Squamous Cell Carcinoma, ICOS = T-cell co-stimulator, IDO1 = Indoleamine 2,3-dioxygenase 1, JAK2 = Janus Kinase 2, MDSCs = Myeloid-Derived Suppressor cells, MTD = Maximum Tolerated Dose, MUC-1 = Mucin-1, cell surface associated, N = Number, NSCLC = Non-Small Cell Lung Cancer, ORR = Overall Response Rate, OS = Overall Survival, PD-1 = Programmed Death-1, PD-L1 = Programmed Death-1 Ligand, PDE5 = Phosphodiesterase 5, PFS = Progression Free Survival, PI3Kγ = Phosphoinositide 3-Kinase γ, Pts = Patients, RD = Recommended Dose, R/M = Recurrent/Metastatic, STAT3 = Signal transducer and activator of transcription 3, TAMs = Tumor Associated Macrophages, TLR8 = Toll-like Receptor 8, Tregs = T regulatory cells, VEGF = Vascular Endothelial Growth Factor, VEGFR = Vascular Endothelial Growth Factor Receptor.