Table 3.
Clinical trials of the un-approved EGFR antibodies.
| Tumor type | Drug X | Combination therapy drugs | Route, dose | Comparison (medication group and control group) | Efficacy (n/N, % of CR, PR, SD, NR), survival benefit = months | Safety (list grade III and IV adverse events) | Phase I, II, III (n) |
References/ clinical trials |
|---|---|---|---|---|---|---|---|---|
| Recurrent glioblastoma | Depatuxizumab mafodotin | Temozolomide | Depatux-m (0.5–1.5 mg/kg) | Single arm increments | OR was 14.3%, PFS was 25.2%, and OS was 69.1%. | Grades 3/4 AEs occurring in 22% of patients | Phase I multicenter trial (60) | (63) |
| Advanced solid tumors | Depatuxizumab (ABT-806) | NR | 2 mg/kg every other week (eow) to escalate to 6, 12, 18, and 24 mg/kg eow. | Single arm increments | Median time to progression was 55 vs. 43 days. No OR occurred | Grade 3/4 AEs n = 11 (22%) | Phase I (49) | (64) |
| Squamous cell carcinoma of the head and neck | Duligotuzumab | Cetuximab | Duligotuzumab (1,100 mg IV, q2w) | Both arms (duligotuzumab vs. cetuximab 59:62) | PFS was 4.2 vs. 4.0 months; HR: 1.23, OS was 7.2 vs. 8.7 months; HR 1.15 and ORR (12 vs. 14.5%) | Duligotuzumab vs. cetuximab, and GI disorders (17 vs. 7%), infections (22 vs. 11.5%) | Phase II (121) | (65) |
| Metastatic colorectal cancer | Sym004 (futuximab + modotuximab) | BSC or 5-FU or Capecitabine | A: Sym004 (12 mg/kg) B: Sym004 (9/6 mg/kg) |
A: Sym004 (12 mg/kg) B:Sym004 (9/6 mg/kg) C: Standard of Care |
OS = 7.9 vs. 10.3 vs. 9.6 CR = 0 (0) vs. 0 (0) vs. 1 (1.2) PR = 11 (13.3) vs. 8 (9.3) vs. 1 (1.2) |
A: 58 (69.9%) vs. B: 41 (48.8%) vs. C: 9 (11.5%) | Phase II (254) | NCT02083653 |
| Head and neck squamous cell carcinoma | Imgatuzumab (GA201) | Cetuximab | Imgatuzumab (700 mg) or (1,400 mg) | Imgatuzumab (700 mg) vs. Imgatuzumab (1,400 mg) vs. Cetuximab | Downregulation of EGFR−35% [700 mg]; −42% [1,400 mg]; −21% [cetuximab] | 10 (48%) vs. 14 (70%) vs. 10 (56%) | n = 59 | (66) |
| Advanced gastric and esophagogastric adenocarcinomas | Matuzumab (EMD 72000) | 5-fluorouracil, leucovorin and cisplatin (PLF) | 400 mg matuzumab in combination with PLF or 800 mg matuzumab | 400 mg dose n = 7; 800 mg dose n = 8 | The best confirmed overall response rate was 26.7% | 0 (0) vs. 2 (13.3%) | Phase I (15) | (67) |
| Advanced non-small cell lung cancer | Nimotuzumab (h-R3) | Gefitinib | 200 mg, i.v. weekly | Nimotuzumab plus gefitinib (78) vs. gefitinib alone (77) | PR = 13 (16.7%) vs. 17 (22.1%) SD = 29 (37.2%) vs. 33 (42.9%) OS = 14.0 (9.7–18.2) vs. 13.5 (11.3–15.7) |
11 (14.3%) vs. 12 (15.6%) | Phase II (155) | (68) |
| Squamous-cell carcinoma of the head and neck | Zalutumumab | Best supportive care | Initially 8 mg/kg and followed doses of 4 mg/kg | Zalutumumab plus BSC (191) vs. BSC alone (95) | OS = 6.7 (5.8–7.0) vs. 5.2 (4.1–6.4) | (39 [21%] vs. 0) | Phase III (286) | (69) |
| Solid tumors | Tomuzotuximab | NR | Weekly (12–1,370 mg) or 2-weekly (990 mg) | A three-plus-three dose escalation design. | 12 SD, 1 PR, 1 CR, and 2 prolonged control of their non-measurable disease. | Infusion-related reactions 3 grade, 12% | Phase I (41) | (70) |
BSC, best supportive care; FOLFOX, folinic acid (leucovorin), fluorouracil, oxaliplatin; FU, fluorouracil; HNSCC, head and neck squamous-cell carcinoma; NR, not reported; NSCLC, non-small-cell lung cancer; PR, Response rate; OS, Median overall survival; PFS, Median progression free survival; DCR, disease control rate; CR, complete response; XRT, X-ray Radiation Therapy; RT, Radiation Therapy.