Table 1.
Active and completed multi-institutional clinical trials of EGFR-targeted therapies in the past 10 years
| Drug | Phase/Design | Target | Population | Endpoints | Results |
|---|---|---|---|---|---|
| Neratinib7 NCT02977780 | II, randomized, adaptive platform trial, experimental arms (neratinib, abemaciclib, CC-115), control arm (TMZ) | EGFR amplification (neratinib), CDK4/6 amplification (abemaciclib), PI3K/ Akt/mTOR (CC-115) | Newly diagnosed glioblastoma, IDH1 wild-type, unmethylated MGMT promoter | OS | Active, recruiting |
| Rindopepimut (ReACT) NCT014983288 | II, double-blind, randomized, experimental arm (bevacizumab+rindopepimut), control arm (bevacizumab+KLH) | EGFRvIII (rindopepimut), VEGF (bevacizumab) | First or second recurrence, bevacizumab naïve, EGFRvIII-positive, n = 73 | PFS6 | 28% for rindo+bev and 16% in control arm (P = 0.12) |
| Rindopepimut (ACT IV)9 NCT01480479 | III, double-blind, randomized, experimental arm (adjuvant TMZ+rindopepimut), control arm (adjuvant TMZ+KLH) | EGFRvIII | Newly diagnosed glioblastoma, EGFRvIII positive, completed standard chemoradiation, n = 745 | OS | Terminated |
| Depatux-M INTELLANCE 2 NCT02343406 | II, randomized, open-label, experimental arms (Depatux-M, Depatux- M+TMZ), control arm (TMZ or lomustine) | EGFR amplification (anti-EGFR ADC) | First recurrence, EGFR amplification, n = 260 | OS | 2-year survival 19.8% in Depatux- M+TMZ, 5.2% in control arm P = 0.017 |
| Depatux-M INTELLANCE 1 NCT02573324 | III, double-blind, randomized, experimental arm (Depatux-M + TMZ concurrent with RT followed by adjuvant Depatux-M +TMZ), control arm (RT+TMZ+placebo then TMZ+placebo) | EGFR amplification (anti-EGFR ADC) | Newly diagnosed glioblastoma, EGFR amplification | OS | Terminated |
| Afatinib10 | I/II, phase II 3 arms; experimental arms (afatinib+TMZ, afatinib alone), control arm (TMZ) | EGFR amplification | First recurrence, n = 39 (AFA/TMZ), n = 39 (TMZ), n = 41 (AFA) | PFS6 | 23% TMZ, 3% AFA, 10% AFA+TMZ |
Abbreviations: ADC, antibody–drug conjugate; AFA, afatinib; CDK, cyclin dependent kinase; KLH, keyhole limpet hemocyanin; PI3K/Akt/mTOR, phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin; PFS6, six-month progression-free survival; VEGF, vascular endothelial growth factor.