Table 1.
Selected clinical trials of SMO inhibitors in cancer
| SMO inhibitor | Phase | Indication | Statusa | Adverse events | Dose/efficacy | NCT # identifierb |
|---|---|---|---|---|---|---|
| Vismodegib (GDC-0449) | 1 | Locally advanced or metastatic solid tumours (n = 68) | Completed | Frequent grade 1/2 AEs: muscle spasms, dysgeusia, fatigue, alopecia, nausea, decreased appetite, diarrhoea; grade 3/4 AEs occurred in 37% of patients | Recommended phase 2 dose: 150 mg/day; ORR: 29% (58% in BCC, 1 unconfirmed response in MB) (Ref. 246) | NCT00607724 |
| 1 | Recurrent or refractory childhood MB | Completed | Recommended dose: 150–300 mg (Ref. 251) | NCT00822458 | ||
| 1 | High-risk first remission or relapsed multiple myeloma | Ongoing | NCT01330173 | |||
| 2 | Recurrent of refractory adult MB | Ongoing | NCT00939484 | |||
| 2 | Locally advanced or metastatic BCC (n = 96) | Ongoing | Frequent grade 1/2 AEs (>30% of patients): muscle spasms, alopecia, dysgeusia, weight loss, fatigue; grade 3/4 AEs were reported in 25% patients | Response rate: 43% for locally advanced BCC; 30% for metastatic BCC (Ref. 247) | NCT00833417 | |
| 2 | Ovarian cancer in second or third remission (n = 104) | Completed | Common grade 1/2 AEs: dysgeusia, ageusia, muscle spasms, alopecia; grade 3/4 AEs occurred in 23% (vismodegib) and 11.5% (placebo) of patients | Median PFS: vismodegib 7.5 months compared with placebo 5.8 months (Ref. 249) | NCT00739661 | |
| 2 | BCNS (n = 41) | Ongoing | Frequent AEs: dysgeusia, muscle cramps, alopecia, weight loss | Per patient rate of newly formed BCCs: 2 in vismodegib, 29 in placebo (Ref. 244) | NCT00957229 | |
| 2 | Advanced chondrosarcoma | Ongoing | Common grade 1/2 AEs: myalgia, dysgeusia and alopecia; 2 patients had reversible grade 3/4 ALT or AST increase | Clinical benefit rate: 26%; median PFS: 3.5 months; median OS: 12.4 months (Ref. 250) | NCT01267955 | |
| Sonidegib (LDE-225) | 1 | Advanced solid tumours, including MB and BCC (n = 103) | Completed | Common grade 1/2 AEs: muscle spasms, myalgia, gastrointestinal toxicities, increased liver enzymes, dysgeusia, fatigue, alopecia | MTD: 800 mg/day; DLT: reversible grade 3–4 elevated serum creatine kinase (Ref. 248) | NCT00880308 |
| 1/2 | Advanced solid tumours in children, including MB | Ongoing | NCT01125800 | |||
| 2 | Relapsed/refractory acute leukaemia | Ongoing | NCT01826214 | |||
| 2 | ER/HER2-breast cancer | Recruiting | NCT01757327 | |||
| BMS-833923 | 1 | Solid tumours | Completed | NCT01413906 | ||
| 1 | Advanced or metastatic solid tumours, including BCC and BCNS | Completed | NCT00670189 | |||
| PF-04449913 | 1 | Advanced solid tumours (n = 23) | Completed | Frequent grade 1/2 AEs: dysgeusia, fatigue, decrease appetite, nausea, dizziness, dehydration, diarrhoea | Recommended dose: 80–320 mg/day (Ref. 300) | NCT01286467 |
| 1 | Haematologic malignancies | Completed | NCT00953758 | |||
| LY2940680 | 1 | Advanced solid tumours | Ongoing | NCT01226485 |
Abbreviations: AEs, adverse events; ALT, alanine transaminase; AST, aspartate transaminase; BCC, basal cell carcinoma; BCNS, basal cell nevus syndrome; DLT, dose-limiting toxicity; ER, oestrogen receptor; HER2, human epidermal growth factor receptor 2; MB, medulloblastoma; MTD, maximum tolerated dose; ORR, overall response rate; OS, overall survival; PFS, progression free survival.
aStatus assessed on December 10th 2014; all ongoing trials are not recruiting.
bNCT # Identifier at http://clinicaltrials.gov.