Table 3.

Related grade 3/4 adverse events (AEs)

Patients with C1-related grade (Gr) 3/4 AEsPatients with C≥2-related Gr 3/4 AEs
Dose levelMK-2206Selumetinibn (evaluable for safety)DLT n (%)EventnEventn
QOD-145 mg QOD75 mg BID4 (3)2 (66.7)Gr 3 rash2aGr 3 ALT/AST elevation1
QOD-145 mg QOD75 mg QD6 (6)0 (0)Gr 3 diarrhea1None0
QW-190 mg QW75 mg BID9 (7)3 (42.8)bGr 3 stomatitis1aGr 3 anemia1
Gr 3 rash1aGr 3 fatigue1
Gr 3 retinal pigment epithelium detachmentb1
QW-1a90 mg QW75 mg QD7 (6)1 (16.7)Gr 3 diarrhea1aGr 3 ALT elevation1
QW-1b90 mg QW50 mg BID7 (6)2 (33.3)Gr 3 rash2aGr 3 CPK elevation1
Gr 3 diarrhea1
QW-1c90 mg QW100 mg QD3 (3)0 (0)None0None0
QW-1d90 mg QW150 mg QD3 (3)2 (66.7)Gr 4 lipase elevation1aNone0
Gr 3 retinal pigment epithelium detachment1a
QW-1ec135 mg QW100 mg QD17 (17)3 (17.6)Gr 3 fatigue1aGr 3 ALT/AST elevation1
Gr 3 dry skin1
Gr 3 pruritus1
Gr 3 rash3
G3 lymphocyte count decreased1
Gr 3 pruritus1
Gr 3 rash3a (1 DLT)
Gr 3 stomatitis1a
QW-1f100 mg QW100 mg QD6 (6)0 (0)NoneNone0

NOTE: No grade 5 events considered by the investigator to be related to either drug were reported.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; CPK, creatine phosphokinase; DLT, dose-limiting toxicity; QD, once daily; QW, once weekly.

  • aEvent counted as DLT.

  • bOne grade 2 DLT of retinal pigment epithelium detachment was observed during cycle 1 in the same patient who experienced a grade 3 event after beginning cycle 2.

  • cDose considered the MTD for the combination; 6 enrolled in dose-escalation period, 11 KRAS-mutant NSCLCs enrolled in confirmation period.