Table 2.

Toxicities of linsitinib/erlotinib combination

A. DLTs
Linsitinib/erlotinib dose (mg)Grade of AEaRelation to treatment
S1
600/100 QDG3 hyperglycemiabLinsitinib
600/100 QDG3 increased ASTLinsitinib and erlotinib
G3 increased ALPLinsitinib and erlotinib
G2 increased ALTLinsitinib and erlotinib
450/100 QDG4 increased ALTcLinsitinib and erlotinib
G4 increased ASTcLinsitinib and erlotinib
450/150 QDG3 prolonged QTc intervalLinsitinib
S2
400/150 QDG2 prolonged QTc intervaldLinsitinib
400/150 QDG3 prolonged QTc intervalLinsitinib
S3
150 BID /150 QDG3 anorexiaLinsitinib and erlotinib
B. Treatment-emergent AEs occurring in at least 5% of patients
AES1 (n = 40)S2 (n = 24)S3 (n = 12)NSCLC expansion (n = 15)Total (n = 91)
Fatigue29 (72)18 (75)7 (58)8 (53)62 (68)
Malaise2 (5)2 (8)1 (8)1 (7)6 (7)
Nausea25 (62)11 (46)9 (75)8 (53)53 (58)
Vomiting13 (32)9 (38)8 (67)6 (40)36 (40)
Diarrhea28 (70)16 (67)9 (75)13 (87)66 (73)
Rash32 (80)20 (83)11 (92)13 (87)76 (84)
Pruritis11 (28)8 (33)6 (50)5 (33)30 (33)
Anorexia12 (30)11 (46)5 (42)4 (27)32 (35)
Dehydration9 (22)2 (8)4 (33)1 (7)16 (18)
Hyperglycemia3 (8)002 (13)5 (5)
QTc prolongation5 (12)3 (12)01 (7)9 (10)
ALT elevation3 (8)1 (4)2 (17)06 (7)
AST elevation3 (8)1 (4)2 (17)06 (7)
  • NOTE: Table shows number (%) of patients experiencing each AE.

  • Abbreviations: ALP, alkaline phosphatase; BID, twice daily; G, grade; QD, once daily.

  • aUnless otherwise noted, DLT defined by ≥grade 3 toxicity.

  • bGlucose intolerance: Fasting glucose >250 mg/dL (13.9 mmol/L).

  • cInability to complete designated schedule in first treatment period due to drug-related toxicity.

  • dInterruption of dosing for ≥5 continuous days within first 21 days due to drug-related toxicity.