Table 1 Failed clinical trials for MAPK pathway inhibitors in HNSCC patients.
From: Precision drugging of the MAPK pathway in head and neck cancer
Clinical trial ID | Clinical trial (tumor type; N) | Target(s) | Drug(s) | No. of HNSCC patients | HNSCC patient outcome | Outcomes of non-HNSCC patients | Ref |
|---|---|---|---|---|---|---|---|
NCT00454090 | Phase I (multiple solid tumors; N = 82) | MEK1/2 | AZD8330 | 8 | Not specified | Manageable toxicity at 20 mg BID (MTD); 1 melanoma case with partial response; 22 other patients with stable disease (>3mo). | |
NCT00085787 | Phase I (multiple solid tumors; N = 57) | MEK1/2 | Selumetinib | 2 | Not specified | 19 patients had stable disease at the end of cycle 2 (≥ 5mo of stable disease in 9 patients). | |
NCT02586987 | Phase I (multiple solid tumors; N = 58) | MEK1/2 | Selumetinib [with MEDI4736; with MEDI4736 + Tremelimumab (anti-CTLA4 antibody)] | N.A. | N.A. | “Completed” but result unavailable. | N.A. |
NCT00467779 | Phase I (multiple solid tumors; N = 97) | MEK1/2 | Cobimetinib | 5 | No objective responses reported | In melanoma patients, 1 complete and 6 partial responses. | |
NCT03264066 | Phase I (multiple solid tumors; N = 88) | MEK1/2 | Cobimetinib [with Atezolizumab (anti-PD-L1 antibody)] | N.A. | N.A. | “Completed” but result unavailable. | N.A. |
NCT00948467 | Phase I (multiple solid tumors; N = 51) | MEK1/2 | TAK-733 | 1 | No objective responses reported | 2 partial responses (cutaneous melanoma). | |
NCT01358331 | Phase I (multiple solid tumors; N = 25) | ERK1/2 | MK-8353 | 1 | Discontinued after 56 days of treatment (200 mg BID) due to progression | 3 BRAF p.V600E-mutant melanoma patients out of 15 evaluable patients demonstrated partial responses. |
