Table 4. ARCHER program for the development of dacomitinib in NSCLC.
| ARCHER | Design title | Population | Endpoints | Ref. |
|---|---|---|---|---|
| 1001 | Phase I dose-escalation study of the pan-HER inhibitor, PF299804, in patients with advanced malignant solid tumors | 121 (U.S) | RP2D =45 mg orally once daily | (66) |
| 1003 | Safety and efficacy of dacomitinib in Korean patients with KRAS wild-type advanced NSCLC refractory to chemotherapy and erlotinib or gefitinib: a phase I/II trial | 12 (South Korea) | RP2D =45 mg orally once daily; PFS at 4 mo =47.2%; median PFS 15.4 weeks, median OS =46.3 weeks; ORR 17.1% | (67) |
| 1005 | Phase I and pharmacokinetic study of dacomitinib (PF-00299804), an oral irreversible, pan-HER inhibitor in Japanese patients with advanced solid tumors | 13 (Japan) | RP2D = 45 mg orally once daily | (68) |
| 1002 | A phase 2 trial of dacomitinib (PF-00299804), an oral, irreversible pan-HER inhibitor, in patients with advanced NSCLC after failure of prior chemotherapy and erlotinib | 66. ADC: 4.8%; non-ADC: 6.3%; EGFR-mutant: 8% | ADC: ORR=5%; non-ADC: ORR=6%; median PFS =12 weeks; median PFS for EGFR-mutant =18 weeks | (69) |
| 1017 | Dacomitinib as first-line treatment in patients with clinically or molecularly selected advanced NSCLC: a multicenter, open-label, phase 2 trial | 89. EGFR-mutant: 60% (51% with del 19 or L858R) | Median PFS=11.5 mo; median PFS for EGFR-mutant =18.2 mo; median OS= 29.5 mo; median OS for EGFR-mutant =40.2 mo; ORR =53.9%; ORR for EGFR-mutant =75.6% | (70) |
| 1028 | Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-HER inhibitor, vs. erlotinib in patients with advanced NSCLC | 188. EGFR-mutant: 15.9% | Median PFS=2.86 mo (dacomitinib) vs. 1.91 mo (erlotinib); P= 0.012; KRAS wild-type/EGFR any type: median PFS =3.71 mo (dacomitinib) vs. 1.91 mo (erlotinib); P= 0.006; KRAS wild-type/EGFR wild-type: median PFS =2.21 mo (dacomitinib) vs. 1.84 mo (erlotinib); P=0.043; median OS =9.53 mo (dacomitinib) vs. 7.44 mo (erlotinib); ns | (71) |
| 1009 | Dacomitinib vs. erlotinib in patients with advanced-stage, previously treated NSCLC (ARCHER 1009): a randomized, double-blind, phase 3 trial | 878. EGFR-mutant: 10% | Median PFS =2.6 mo for both dacomitinib and erlotinib; KRAS wild-type: median PFS =2.6 mo for both dacomitinib and erlotinib; median OS =7.9 mo (dacomitinib) vs. 8.4 mo (erlotinib); ns; KRAS wild-type: median OS =8.1 mo (dacomitinib) vs. 8.5 mo (erlotinib); ns | (72) |
| BR-26 | Dacomitinib compared with placebo in pretreated patients with advanced or metastatic NSCLC (NCIC CTG BR.26): a double-blind, randomized, phase 3 trial | 720. EGFR-mutant: 25.3% | Median OS =2.38 mo (dacomitinib) vs. 6.31 mo (placebo); ns. No differences in the subgroups | (73) |
| 1050 | Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive NSCLC (ARCHER 1050): a randomized, open-label, phase 3 trial | 452 EGFR-mutant | Median PFS =14.7 mo (dacomitinib) vs. 9.2 mo (gefitinib); P<0.0001; median PFS =34.1 mo (dacomitinib) vs. 26.8 mo (gefitinib); P=0.0438 | (57,58) |
RP2D, recommended phase II dose; mo, months; ADC, adenocarcinoma; ns, not significant; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; PFS, progression-free survival; OS, overall survival; ORR, objective response rate.