Table 2.
SMI Targets and Clinical Trials in HNSCC.
| Target | Drug | Phase | Trial | Intent | Outcome |
|---|---|---|---|---|---|
| STAT3 | AZD9150 | 1b/2 | NCT02499328 [81] | Combination ASD9150 + MED14736 (duravalumab) vs. MED14736 alone; in platinum refractory recurrent metastatic HNSCC | Acceptable toxicity profile. Combination therapy more effective than PD-L1 monotherapy |
| STING | MK-1454 | 1 | NCT03010176 [82] | Combination MK-1454 (ulveostinag) + pembrilizumab vs. MK-1454 monotherapy; in advanced HNSCC | Acceptable toxicity profile. Combination therapy more effective (DCR 48%) than monotherapy (DCR 20%) |
| PPAR-α | TPST-1120 | 1/1b | 03829436 [83] | Combination TPST-1120 + nivolumab vs. TPST-1120 monotherapy; in advanced solid tumors; including HNSCC | Acceptable toxicity (several patients suffered Grade 3 Adverse reactions. Optimal disease response in combination therapy (38%) |
| RTKs | AL3818 | 2 | NCT04999800 [84] | Combination AL3818 (analotinib) + pembrolizumab; as a first line therapy for platinum refractory recurrent or metastatic HNSCC | Manageable side effects. Encouraging anti-tumor activity. ORR: 46.7% (7/15) & DCR: 100% Median PFS & OS not reached (median follow-up: 8.2 months. |
| RTKs | Afatinib | 3 | NCT01345682 [85] | LUX-Head & Neck 1: second-line afatinib therapy vs. methotrexate for platinum refractory recurrent/metastatic HNSCC |
n = 483 patients. Median PFS: afatinib over methotrexate (2.7 months vs. 1.6 months) Afatinib more effective in all tumor subsets except HPV + OPSCC |
| AHR | BAY2416964 | 1 | NCT04069026 [86] | AHR antagonist: safety and tumor response study in advanced HNSCC & nSCLC | Well tolerated at all dose regimes. Initial evaluation of biomarkers shows inhibition of AHR and modulation of immune functions. Encouraging preliminary anti-tumor activity in heavily pretreated patients. |