Table 2.

Dose escalation and determination of maximum tolerated dose (MTD).

	Treated patientsa, n	Evaluable patientsb, n	Patients with DLTs, n	DLTs
QD dosing schedule
2 mg	3	3	0	–
4 mg	7	7	1	Grade 3 hyperglycaemia
6 mgc (MTD)	13	10	4	Grade 3 maculo-papular rash; grade 3 diarrhoea; grade 3 asthenia; grade 5 ventricular fibrillation/cardiac arrest
7 mg	8	5	2	Grade 3 hyperglycaemia and grade 4 anaemia; grade 3 maculo-papular rash
QW dosing schedule
7 mg	3	3	0	–
10 mg	3	3	0	–
15 mg	3	3	0	–
20 mg	3	3	0	–
30 mg	3	3	0	–
40 mg (MTD)	15	12	2	Grade 3 dry mouth and fatigue; grade 3 asthenia
QD × 3dQW dosing schedule
6 mg	3	3	0	–
9 mg (MTD)	8	6	1	Grade 3 hypophosphatemia
12 mg	6	6	2	Grade 3 stomatitis and grade 3 dehydration; grade 3 asthenia
16 mg	12	11d	1	Grade 3 stomatitis
20 mg	4	3	2	Grade 3 stomatitis; grade 3 stomatitis
QD × 5dQW dosing schedule
7 mg (MTD)	6	6	0	–
10 mg	13	13	4	Grade 2 stomatitis; grade 3 stomatitis; grade 3 asthenia; grade 3 stomatitis; grade 3 fatigue
13 mg	3	3	3	Grade 3 fatigue; grade 3 asthenia; grade 3 stomatitis

AE adverse event, DLT dose-limiting toxicity, QD once daily, QD × 3dQW once daily for 3 days on and 4 days off each week, QD × 5dQW once daily for 5 days on and 2 days off each week, QW once weekly.

^aInitial dose cohorts for each of the alternate dosing schedules prior to a protocol amendment enrolled a single patient. If grade ≥ 2 AE, regardless of relatedness to sapanisertib was observed in any single-patient cohort, an additional 2–5 patients were assigned to that cohort and subsequent dose cohorts in that treatment arm would include 3–6 patients.

^bPatients who received ≥75% of the planned doses of sapanisertib in cycle 1 or stopped study drug before receiving 75% of the planned doses because of a study treatment-related AE considered a DLT.

^cPatients were enrolled into the 6 mg QD dosing schedule after the 7 mg QD dosing schedule.

^dFive patients required dose modification due to AEs.