Table 1.
Clinical trials of IGF-1 inhibitors as single agents.
| Cancer type | Drug | Drug Type | Clinical trial Phase | Number of patiens | Response | Trial ID | Ref. |
|---|---|---|---|---|---|---|---|
| Postmenopausal women with hormone receptor–positive breast cancer | Cixutumumab | Anti-IGF-1R mAb | II | n=93(31 in the cixutumumab alone group) | No significant clinical effect observed with cixutumumab alone | NCT00728949 | (92) |
| Advanced hepatocellular carcinoma | Cixutumumab | Anti-IGF-1R mAb | II | Qnly stage 1 was accrued: n= 24 | No significant clinical effect | NCT00639509 | (93) |
| Refractory Solid Tumors | Cixutumumab | Anti-IGF-1R mAb | II | n=116 | Limited objective single-agent activity of cixutumumab was observed; PR:20%(neuroblastoma with only MIBG evaluable disease ), SD:15%(patients with a variety of solid tumor types) |
NCT00831844 | (94) |
| Recurrent or refractory TETs | Cixutumumab | Anti-IGF-1R mAb | II | n=49(37 thymomas;12 thymic carcinomas) | PR :14%,SD :76%(thymoma cohort); PR:0,SD:42%(thymic carcinoma cohort) |
NCT00965250 | (95) |
| Rhabdomyosar-coma; Leiomyosarcoma; Adipocytic sarcoma; Synovial sarcoma; Ewing family of tumours (including ES-1 and peripheral neuroectodermal tumour) |
Cixutumumab | Anti-IGF-1R mAb | II | n=113(all tiers except adipocytic sarcoma were closed after stage 1 due to futility) | PFR:12%(rhabdomyosarcoma, n = 17), 14%( leiomyosarcoma, n=22), 32%(adipocytic sarcoma, n=37), 18%(synovial sarcoma, n=17), 11%(Ewing family of tumours, n=18) | NCT00668148 | (96) |
| Ewing sarcoma, osteosarcoma and other sarcomas | Figitumumab | Anti-IGF-1R mAb | I/II | Phase Iportion n=31, phase II portion n=107 | phaseIIportion ORR=14.2% | NCT00560235 | (97) |
| Neuroendocrine tumor | MK-0646 | Anti-IGF-1R mAb | II | n=25 | inactive as a single agent | NCT00610129 | (98) |
| Previously treated, locally advanced or metastatic NSCLC of the SCC or AC subtypes | AXL1717 | IGF-1R TKI | II | n=99(58 in the AXL1717 group) | 12-week PFS: 25.9%(AXL1717 group), 39.0%(docetaxel group),without any statistically significant differences | NCT01561456 | (99) |
| Adrenocortical carcinoma | Linsitinib | IGF-1R/INSR TKI | III | n=135 | No difference in overall survival was noted between linsitinib and placebo | NCT00924989 | (100) |
| Metastatic castrate resistant prostate cancer | Linsitinib | IGF-1R/INSR TKI | II | n=18 | No significant PSA or objective response; without any effect on circulating tumor cells or survival benefit |
NCT01533246 | (101) |
| advanced/metastatic solid cancers | Xentuzumab | IGF-1/IGF-2-neutralizing Ab | I | Study 1280.1:n=61; Study 1280.2:n=64 | Preliminary anti-tumour activity; Study 1280.1 part 1:PR(n=2),SD(n=3); Study 1280.1 part2: SD(n=3); Study 1280.2: no objective responses; SD(n=2 in part1) |
NCT01403974; NCT01317420 | (102) |
| advanced solid tumors | xentuzumab | IGF-1/IGF-2-neutralizing Ab | I | n=21 | Preliminary anti-tumour activity; ORR=9.5% SD=19.0% |
NCT02145741 | (103) |
IGF-1R, insulin-like growth factor receptor 1; INSR, insulin receptor; PR, partial response; SD, stable disease; ORR, objective response rate; AE, most common grade 3-4 adverse events; MIBG, meta-iodo-benzyl-guanidine; PFR, progression-free survival rate; TETs, thymic epithelial tumors; TKI, tyrosine kinase inhibitor; NSCLC, non-small cell lung cancer; SCC, squamous cell carcinoma; AC, adenocarcinoma; PFS, progression-free survival.