Table 1.

Clinical trials of SMOis in hematopoietic malignancies

InhibitorDiseaseDosageCombination(Preliminary) resultsClinical trialPhaseStatusReference(s)
BMS-833923 CML 50-200 mg/d Dasatinib 30% of patients who are dasatinib-resistant with chronic phase CML responded to combination treatment (1 with complete cytogenetic response after 47-51 wk) NCT01218477 1/2 Completed 165  
Leukemia Not defined Dasatinib — NCT01357655 2 Terminated — 
Glasdegib AML 100 mg/d Cytarabine/daunorubicin, azacitidine No improvement of OS through addition of glasdegib NCT03416179 3 Completed 170  
AML Not defined SCT + bosutinib, decitabine, enasidenib, ivosidenib, venetoclax, gilteritinib — NCT04655391 Pilot/1b Withdrawn — 
AML 100 mg/d Gemtuzumab ozogamicin or SCT — NCT04168502 3 Recruiting — 
AML 100 mg/d Decitabine — NCT04051996 2 Terminated — 
AML 100 mg/d Gemtuzumab ozogamicin — NCT04093505 3 Recruiting 171  
AML 100 mg/d Gemtuzumab ozogamicin 1 of 3 patients with reduced BM blasts after 1 cycle, no formal response NCT03390296 1b/2 Active 172  
AML 100 mg/d Decitabine, azacitidine, venetoclax — NCT03226418 2 Active, not recruiting 173  
AML Not defined — — NCT04230564 — Withdrawn — 
AML, CML, CMML, MDS, MF 5, 10, 20, 40, 80, 120, 180, 270, 400, or 600 mg/d — Established MTD: 400 mg/d; AEs within the expected range; 2 patients experienced DLT (80 and 600 mg/d); clinical activity in 49% of patients NCT00953758 1 Completed 174,175  
AML, CMML, MDS 50, 75, or 100 mg/d Azacitidine — NCT04842604 (continuation of NCT03416179 and NCT02367456) 3 Active — 
AML, MDS 25, 50, or 100 mg/d LDAC, azacitidine, cytarabine/daunorubicin Glasdegib + LDAC, well-tolerated; glasdegib + azacitidine, well-tolerated; glasdegib + cytarabine/daunorubicin, manageable despite increased severe AEs; low remission rates in glasdegib only cohort, increased in combination cohorts NCT02038777 1 Active, not recruiting 176  
AML, MDS 1b: 100 or 200 mg/d, 2: 100 mg/d LDAC, decitabine, cytarabine/daunorubicin Phase 1b: glasdegib in combination with LDAC or decitabine, well-tolerated; glasdegib + cytarabine/daunorubicin, increased severe AEs, manageable; 31% remission rate across all groups; phase 2: glasdegib + cytarabine/daunorubicin, high CR rate; glasdegib + LDAC, drastically improved CR rate and OS in combination compared to LDAC only (17% vs 2.3% and 8.8 vs 4.9 mo) NCT01546038 1b/2 Completed 159-164  
AML, MDS 100 mg/d Azacitidine Well-tolerated; 20% of patients with AML and 13.3% of patients with MDS achieved CR NCT02367456 1b Completed 177  
AML, MDS 100 mg/d CPX-351 (cytarabine/daunorubicin) — NCT04231851 2 Recruiting — 
AML, MDS 100 mg/d SCT 52% severe AEs, limited ability for glasdegib to prevent relapse in high-risk, post-SCT setting NCT01841333 2 Completed 178  
CML 200, 400, or 600 mg/d Nilotinib Observed SAEs consistent with sonidegib safety profile, no evidence of clinical benefit for the combination
for phase 2 trials 		NCT01456676 1 Completed — 
CMML, MDS 100 mg/d — 31% severe AEs, 54% stable disease, 6.4 mo progression-free survival NCT01842646 2 Completed — 
MF 100 mg/d — 24% severe AEs, no significant spleen volume reduction NCT02226172 1/2 Terminated 179  
Saridegib MF 60, 130, or 110 mg/d — 85% slight spleen size reduction, reduced fibrosis and JAK2V617F allele burden in some patients, too little of a response to further evaluate saridegib as a monotherapy NCT01371617 2 Completed 180  
Sonidegib ALL, AML 2 × 400 or 800 mg/d — 100% of patients experienced ≥1 AE, 71% of patients experienced serious AEs; low CR rate (1.45% of patients), disease progression in 62% of patients NCT01826214 2 Completed — 
MF 400 mg/d Ruxolitinib Well-tolerated; 44% reduction in spleen volume, ruxolitinib and sonidegib combination might provide improved benefit over ruxolitinib monotherapy NCT01787552 1, 2 Completed 166  
MM 400 or 800 mg/d Bortezomib Safety lead-in data did not support continuation of study NCT02254551 2 Terminated — 
MM 400 mg/d SCT, lenalidomide 18% serious AEs; 46% complete response, 73% 2-y progression free survival rate NCT02086552 2 Completed 168  
Myeloid malignancies 400 mg/d Azacitidine AEs within the expected range; remission rates comparable to azacitidine monotherapy, promising progression-free and overall survival NCT02129101 1/1b Completed 181,182  
Ptch1 or SMO mutated hematologic malignancies (except ALL, AML, CML) 800 mg/d — 0% CR rate, 0% 16-week progression-free survival rate NCT02002689 2 Terminated — 
Vismodegib AML 150 mg/d Ribavirin, decitabine Well-tolerated; shortened time to response, partial remissions, blast responses, and stable diseases NCT02073838 2 Completed 169  
AML, MDS 150 mg/d (Cytarabine) Vismodegib well-tolerated; lower-than-expected efficacy for vismodegib monotherapy; no combination therapy performed NCT01880437 1b/2 Terminated 183  
CLL, NHL 150 mg/d — 52% of patients experienced ≥1 AE, 13% of patients experienced serious AEs; rapid disease progression in 90% of patients NCT01944943 2 Terminated 184  
MF 150 mg/d Ruxolitinib Vismodegib well-tolerated; no improvement compared to ruxolitinib monotherapy NCT02593760 1 Completed 167  
MM Not defined SCT — NCT01330173 1 Completed — 
Various Not defined Not defined — NCT03878524 1b Recruiting — 
InhibitorDiseaseDosageCombination(Preliminary) resultsClinical trialPhaseStatusReference(s)
BMS-833923 CML 50-200 mg/d Dasatinib 30% of patients who are dasatinib-resistant with chronic phase CML responded to combination treatment (1 with complete cytogenetic response after 47-51 wk) NCT01218477 1/2 Completed 165  
Leukemia Not defined Dasatinib — NCT01357655 2 Terminated — 
Glasdegib AML 100 mg/d Cytarabine/daunorubicin, azacitidine No improvement of OS through addition of glasdegib NCT03416179 3 Completed 170  
AML Not defined SCT + bosutinib, decitabine, enasidenib, ivosidenib, venetoclax, gilteritinib — NCT04655391 Pilot/1b Withdrawn — 
AML 100 mg/d Gemtuzumab ozogamicin or SCT — NCT04168502 3 Recruiting — 
AML 100 mg/d Decitabine — NCT04051996 2 Terminated — 
AML 100 mg/d Gemtuzumab ozogamicin — NCT04093505 3 Recruiting 171  
AML 100 mg/d Gemtuzumab ozogamicin 1 of 3 patients with reduced BM blasts after 1 cycle, no formal response NCT03390296 1b/2 Active 172  
AML 100 mg/d Decitabine, azacitidine, venetoclax — NCT03226418 2 Active, not recruiting 173  
AML Not defined — — NCT04230564 — Withdrawn — 
AML, CML, CMML, MDS, MF 5, 10, 20, 40, 80, 120, 180, 270, 400, or 600 mg/d — Established MTD: 400 mg/d; AEs within the expected range; 2 patients experienced DLT (80 and 600 mg/d); clinical activity in 49% of patients NCT00953758 1 Completed 174,175  
AML, CMML, MDS 50, 75, or 100 mg/d Azacitidine — NCT04842604 (continuation of NCT03416179 and NCT02367456) 3 Active — 
AML, MDS 25, 50, or 100 mg/d LDAC, azacitidine, cytarabine/daunorubicin Glasdegib + LDAC, well-tolerated; glasdegib + azacitidine, well-tolerated; glasdegib + cytarabine/daunorubicin, manageable despite increased severe AEs; low remission rates in glasdegib only cohort, increased in combination cohorts NCT02038777 1 Active, not recruiting 176  
AML, MDS 1b: 100 or 200 mg/d, 2: 100 mg/d LDAC, decitabine, cytarabine/daunorubicin Phase 1b: glasdegib in combination with LDAC or decitabine, well-tolerated; glasdegib + cytarabine/daunorubicin, increased severe AEs, manageable; 31% remission rate across all groups; phase 2: glasdegib + cytarabine/daunorubicin, high CR rate; glasdegib + LDAC, drastically improved CR rate and OS in combination compared to LDAC only (17% vs 2.3% and 8.8 vs 4.9 mo) NCT01546038 1b/2 Completed 159-164  
AML, MDS 100 mg/d Azacitidine Well-tolerated; 20% of patients with AML and 13.3% of patients with MDS achieved CR NCT02367456 1b Completed 177  
AML, MDS 100 mg/d CPX-351 (cytarabine/daunorubicin) — NCT04231851 2 Recruiting — 
AML, MDS 100 mg/d SCT 52% severe AEs, limited ability for glasdegib to prevent relapse in high-risk, post-SCT setting NCT01841333 2 Completed 178  
CML 200, 400, or 600 mg/d Nilotinib Observed SAEs consistent with sonidegib safety profile, no evidence of clinical benefit for the combination
for phase 2 trials 		NCT01456676 1 Completed — 
CMML, MDS 100 mg/d — 31% severe AEs, 54% stable disease, 6.4 mo progression-free survival NCT01842646 2 Completed — 
MF 100 mg/d — 24% severe AEs, no significant spleen volume reduction NCT02226172 1/2 Terminated 179  
Saridegib MF 60, 130, or 110 mg/d — 85% slight spleen size reduction, reduced fibrosis and JAK2V617F allele burden in some patients, too little of a response to further evaluate saridegib as a monotherapy NCT01371617 2 Completed 180  
Sonidegib ALL, AML 2 × 400 or 800 mg/d — 100% of patients experienced ≥1 AE, 71% of patients experienced serious AEs; low CR rate (1.45% of patients), disease progression in 62% of patients NCT01826214 2 Completed — 
MF 400 mg/d Ruxolitinib Well-tolerated; 44% reduction in spleen volume, ruxolitinib and sonidegib combination might provide improved benefit over ruxolitinib monotherapy NCT01787552 1, 2 Completed 166  
MM 400 or 800 mg/d Bortezomib Safety lead-in data did not support continuation of study NCT02254551 2 Terminated — 
MM 400 mg/d SCT, lenalidomide 18% serious AEs; 46% complete response, 73% 2-y progression free survival rate NCT02086552 2 Completed 168  
Myeloid malignancies 400 mg/d Azacitidine AEs within the expected range; remission rates comparable to azacitidine monotherapy, promising progression-free and overall survival NCT02129101 1/1b Completed 181,182  
Ptch1 or SMO mutated hematologic malignancies (except ALL, AML, CML) 800 mg/d — 0% CR rate, 0% 16-week progression-free survival rate NCT02002689 2 Terminated — 
Vismodegib AML 150 mg/d Ribavirin, decitabine Well-tolerated; shortened time to response, partial remissions, blast responses, and stable diseases NCT02073838 2 Completed 169  
AML, MDS 150 mg/d (Cytarabine) Vismodegib well-tolerated; lower-than-expected efficacy for vismodegib monotherapy; no combination therapy performed NCT01880437 1b/2 Terminated 183  
CLL, NHL 150 mg/d — 52% of patients experienced ≥1 AE, 13% of patients experienced serious AEs; rapid disease progression in 90% of patients NCT01944943 2 Terminated 184  
MF 150 mg/d Ruxolitinib Vismodegib well-tolerated; no improvement compared to ruxolitinib monotherapy NCT02593760 1 Completed 167  
MM Not defined SCT — NCT01330173 1 Completed — 
Various Not defined Not defined — NCT03878524 1b Recruiting — 

AE, adverse event; CR, complete remission; DLT, dose-limiting toxicity; LDAC, low-dose cytarabine; MTD, maximum tolerated dose; OS, overall survival; SAE, severe adverse event; SCT, stem cell transplantation.

View Large
Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal