Table 2.
Toxicities of linsitinib/erlotinib combination
| A. DLTs | |||||
|---|---|---|---|---|---|
|
| |||||
| Linsitinib/erlotinib dose (mg) | Grade of AEa | Relation to treatment | |||
| S1 | |||||
| 600/100 QD | G3 hyperglycemiab | Linsitinib | |||
| 600/100 QD | G3 increased AST | Linsitinib and erlotinib | |||
| G3 increased ALP | Linsitinib and erlotinib | ||||
| G2 increased ALT | Linsitinib and erlotinib | ||||
| 450/100 QD | G4 increased ALTc | Linsitinib and erlotinib | |||
| G4 increased ASTc | Linsitinib and erlotinib | ||||
| 450/150 QD | G3 prolonged QTc interval | Linsitinib | |||
| S2 | |||||
| 400/150 QD | G2 prolonged QTc intervald | Linsitinib | |||
| 400/150 QD | G3 prolonged QTc interval | Linsitinib | |||
| S3 | |||||
| 150 BID/150 QD | G3 anorexia | Linsitinib and erlotinib | |||
| B. Treatment-emergent AEs occurring in at least 5% of patients | |||||
|
| |||||
| AE | S1 (n = 40) | S2 (n = 24) | S3 (n = 12) | NSCLC expansion (n = 15) | Total (n = 91) |
|
| |||||
| Fatigue | 29 (72) | 18 (75) | 7 (58) | 8 (53) | 62 (68) |
| Malaise | 2 (5) | 2 (8) | 1 (8) | 1 (7) | 6 (7) |
| Nausea | 25 (62) | 11 (46) | 9 (75) | 8 (53) | 53 (58) |
| Vomiting | 13 (32) | 9 (38) | 8 (67) | 6 (40) | 36 (40) |
| Diarrhea | 28 (70) | 16 (67) | 9 (75) | 13 (87) | 66 (73) |
| Rash | 32 (80) | 20 (83) | 11 (92) | 13 (87) | 76 (84) |
| Pruritis | 11 (28) | 8 (33) | 6 (50) | 5 (33) | 30 (33) |
| Anorexia | 12 (30) | 11 (46) | 5 (42) | 4 (27) | 32 (35) |
| Dehydration | 9 (22) | 2 (8) | 4 (33) | 1 (7) | 16 (18) |
| Hyperglycemia | 3 (8) | 0 | 0 | 2 (13) | 5 (5) |
| QTc prolongation | 5 (12) | 3 (12) | 0 | 1 (7) | 9 (10) |
| ALT elevation | 3 (8) | 1 (4) | 2 (17) | 0 | 6 (7) |
| AST elevation | 3 (8) | 1 (4) | 2 (17) | 0 | 6 (7) |
NOTE: Table shows number (%) of patients experiencing each AE.
Abbreviations: ALP, alkaline phosphatase; BID, twice daily; G, grade; QD, once daily.
a
Unless otherwise noted, DLT defined by ≥grade 3 toxicity.
b
Glucose intolerance: Fasting glucose >250 mg/dL (13.9 mmol/L).
c
Inability to complete designated schedule in first treatment period due to drug-related toxicity.
d
Interruption of dosing for ≥5 continuous days within first 21 days due to drug-related toxicity.