Trial Outcomes & Findings for Study of MLN8237 in Combination With Irinotecan and Temozolomide (NCT NCT01601535)

NCT ID: NCT01601535

Last Updated: 2019-07-31

Results Overview

The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 54 participants
• Primary outcome timeframe: 21 days, from study day 1
• Results posted on: 2019-07-31

Participant Flow

Participant milestones

Measure	DL 1 alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis optional	DL 1B alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Ph 2 alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Phase 1 STARTED	6	6	6	4	0	0
Phase 1 COMPLETED	0	0	1	0	0	0
Phase 1 NOT COMPLETED	6	6	5	4	0	0
Phase 2 STARTED	0	0	0	0	20	12
Phase 2 COMPLETED	0	0	0	0	1	0
Phase 2 NOT COMPLETED	0	0	0	0	19	12

Reasons for withdrawal

Measure	DL 1 alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis optional	DL 1B alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Ph 2 alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Phase 1 Adverse Event	1	0	2	1	0	0
Phase 1 Withdrawal by Subject	2	1	1	2	0	0
Phase 1 Progressive Disease	2	3	2	1	0	0
Phase 1 Started Another Treatment	1	2	0	0	0	0
Phase 2 Adverse Event	0	0	0	0	5	1
Phase 2 Withdrawal by Subject	0	0	0	0	8	2
Phase 2 Progressive Disease	0	0	0	0	5	7
Phase 2 Started Another Treatment	0	0	0	0	1	2

Baseline Characteristics

Study of MLN8237 in Combination With Irinotecan and Temozolomide

Baseline characteristics by cohort

Measure	DL 1 n=6 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis optional	DL 1B n=6 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 Participants alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Ph 2 n=20 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=12 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Total n=54 Participants Total of all reporting groups
Age, Continuous	8.60 years n=5 Participants	6.81 years n=7 Participants	7.67 years n=5 Participants	6.14 years n=4 Participants	10.74 years n=21 Participants	3.05 years n=8 Participants	7.61 years n=8 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants	6 Participants n=8 Participants	16 Participants n=8 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	14 Participants n=21 Participants	6 Participants n=8 Participants	38 Participants n=8 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	2 Participants n=8 Participants
Race/Ethnicity, Customized Not Hispanic Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=8 Participants	5 Participants n=8 Participants
Race/Ethnicity, Customized Not Hispanic White	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	14 Participants n=21 Participants	12 Participants n=8 Participants	45 Participants n=8 Participants
Race/Ethnicity, Customized Not Hispanic Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants
Race/Ethnicity, Customized Not Hispanic Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	4 participants n=4 Participants	20 participants n=21 Participants	12 participants n=8 Participants	54 participants n=8 Participants
Prior Irinotecan Yes	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	11 Participants n=21 Participants	2 Participants n=8 Participants	18 Participants n=8 Participants
Prior Irinotecan No	3 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants	10 Participants n=8 Participants	36 Participants n=8 Participants
Prior Temozolomide Yes	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	10 Participants n=21 Participants	2 Participants n=8 Participants	17 Participants n=8 Participants
Prior Temozolomide No	3 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants	10 Participants n=8 Participants	37 Participants n=8 Participants

PRIMARY outcome

Timeframe: 21 days, from study day 1

The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy.

Outcome measures

Measure	Phase I n=22 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Maximum Tolerated Dose (MTD) When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma	60 mg/m^2	—	—	—	—	—

PRIMARY outcome

Timeframe: 21 days, from study day 1

The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy.

Outcome measures

Measure	Phase I n=6 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=6 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 Participants alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Dose Limiting Toxicity (DLT) Data Associated With the Determination of the Recommended Phase 2 Dose	2 DLTs	0 DLTs	1 DLTs	2 DLTs	—	—

PRIMARY outcome

Timeframe: 1st week of cycle 1

Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.

Outcome measures

Measure	Phase I n=6 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=6 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 Participants alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=12 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Day 4 Trough, Day 5 Trough and Cmax Alisertib Day 4 trough	0.48 µM Interval 0.09 to 0.98	0.35 µM Interval 0.13 to 1.38	0.3 µM Interval 0.22 to 4.07	0.73 µM Interval 0.15 to 1.35	0.47 µM Interval 0.09 to 3.37	—
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Day 4 Trough, Day 5 Trough and Cmax Alisertib Day 5 trough	0.37 µM Interval 0.12 to 1.36	0.36 µM Interval 0.18 to 0.65	0.2 µM Interval 0.05 to 3.31	0.69 µM Interval 0.25 to 1.27	0.58 µM Interval 0.09 to 3.2	—
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Day 4 Trough, Day 5 Trough and Cmax Alisertib Cmax	2.56 µM Interval 1.91 to 5.92	2.39 µM Interval 1.72 to 5.92	3.77 µM Interval 2.16 to 6.76	4.94 µM Interval 3.99 to 6.22	8.66 µM Interval 3.49 to 11.39	—

PRIMARY outcome

Timeframe: 1st week of cycle 1

Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.

Outcome measures

Measure	Phase I n=6 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=6 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 Participants alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=12 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Tmax and Half-life Alisertib Tmax	2.04 hour Interval 1.12 to 6.93	1.74 hour Interval 0.65 to 2.9	2.5 hour Interval 0.97 to 4.0	2.52 hour Interval 2.0 to 3.03	2 hour Interval 0.5 to 4.0	—
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Tmax and Half-life Alisertib Half-life	7.20 hour Interval 5.22 to 9.83	8.61 hour Interval 4.2 to 18.2	6.19 hour Interval 3.65 to 20.28	8.54 hour Interval 5.35 to 10.05	8.34 hour Interval 4.28 to 16.89	—

PRIMARY outcome

Timeframe: 1st week of cycle 1

Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.

Outcome measures

Measure	Phase I n=6 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=6 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 Participants alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=12 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib AUC	28.15 µM•hour Interval 16.9 to 65.5	21 µM•hour Interval 15.4 to 44.9	30.71 µM•hour Interval 19.61 to 117.03	47.73 µM•hour Interval 32.71 to 84.67	58.15 µM•hour Interval 32.03 to 144.72	—

PRIMARY outcome

Timeframe: 1st week of cycle 1

Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.

Outcome measures

Measure	Phase I n=6 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=6 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 Participants alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=12 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=8 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Cmax, APC Cmax, SN-38 Cmax, and SN-38G Cmax Irinotecan Cmax	722 ng/mL Interval 502.0 to 880.0	703 ng/mL Interval 642.0 to	1,238 ng/mL Interval 493.0 to	784 ng/mL Interval 546.0 to 987.0	881 ng/mL Interval 490.0 to	732 ng/mL Interval 422.0 to 861.0
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Cmax, APC Cmax, SN-38 Cmax, and SN-38G Cmax APC Cmax	61.2 ng/mL Interval 23.1 to 480.4	59.8 ng/mL Interval 28.2 to 105.0	55.8 ng/mL Interval 25.7 to 76.3	43.4 ng/mL Interval 29.1 to 49.4	57.1 ng/mL Interval 25.7 to 132.0	51.4 ng/mL Interval 15.0 to 98.2
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Cmax, APC Cmax, SN-38 Cmax, and SN-38G Cmax SN-38 Cmax	9.5 ng/mL Interval 6.6 to 18.7	12.6 ng/mL Interval 5.8 to 16.5	12.0 ng/mL Interval 8.8 to 14.7	11.7 ng/mL Interval 7.0 to 13.8	10.4 ng/mL Interval 5.19 to 32.6	8.26 ng/mL Interval 4.62 to 33.1
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Cmax, APC Cmax, SN-38 Cmax, and SN-38G Cmax SN-38G Cmax	18.2 ng/mL Interval 16.0 to 46.9	16.9 ng/mL Interval 4.8 to 23.7	13.8 ng/mL Interval 7.0 to 26.8	13.0 ng/mL Interval 10.4 to 24.0	12.8 ng/mL Interval 6.96 to 50.5	15.2 ng/mL Interval 4.83 to 46.7

PRIMARY outcome

Timeframe: 1st week of cycle 1

Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.

Outcome measures

Measure	Phase I n=6 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=6 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 Participants alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=12 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=8 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan AUC, APC AUC, SN-38 AUC, and SN-38G AUC Irinotecan AUC	3,702 h·ng/mL	2,680 h·ng/mL	3,957 h·ng/mL	2,615 h·ng/mL	3,533 h·ng/mL	3,121 h·ng/mL
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan AUC, APC AUC, SN-38 AUC, and SN-38G AUC APC AUC	571 h·ng/mL Interval 248.0 to	477 h·ng/mL Interval 197.0 to	511 h·ng/mL Interval 293.0 to 821.0	418 h·ng/mL Interval 299.0 to 457.0	511 h·ng/mL Interval 293.0 to	616 h·ng/mL Interval 221.0 to 985.0
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan AUC, APC AUC, SN-38 AUC, and SN-38G AUC SN-38 AUC	63.2 h·ng/mL Interval 20.5 to 294.6	52.9 h·ng/mL Interval 28.4 to 119.6	80.8 h·ng/mL Interval 35.0 to 109.9	72.0 h·ng/mL Interval 62.6 to 102.0	90.0 h·ng/mL Interval 35.0 to 235.0	56.7 h·ng/mL Interval 26.2 to 398.0
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan AUC, APC AUC, SN-38 AUC, and SN-38G AUC SN-38G AUC	206.5 h·ng/mL Interval 124.3 to 325.3	97.6 h·ng/mL Interval 53.8 to 243.6	141.8 h·ng/mL Interval 77.5 to 298.1	134.4 h·ng/mL Interval 101.1 to 237.8	132 h·ng/mL Interval 71.0 to 498.0	136 h·ng/mL Interval 74.6 to 673.0

PRIMARY outcome

Timeframe: 1st week of cycle 1

Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.

Outcome measures

Measure	Phase I n=6 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=6 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 Participants alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=12 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=8 Participants alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Clearance	14.0 L/h Interval 8.8 to 29.4	15.7 L/h Interval 4.6 to 27.3	10.4 L/h Interval 9.0 to 31.4	16.0 L/h Interval 12.6 to 20.1	12.6 L/h Interval 7.65 to 31.7	10.3 L/h Interval 4.12 to 20.9

PRIMARY outcome

Timeframe: Cycles repeated every 21 days for up to 34 cycles.

Population: The analysis was performed on 19 phase II patients, with 1 inevaluable patient excluded.

Response was graded according to version 1.2 of the NANT response criteria that classifies patients as having one of the following overall response categories based upon underlying response at soft tissue sites, MIBG positive sites, and bone marrow disease: complete response (CR); CR with minimal residual disease (CR-MRD); partial response (PR); minor response (MR); stable disease (SD); and progressive disease (PD). These criteria utilize RECIST criteria for measurable tumors, Curie score for MIBG scan response, and bone marrow (BM) morphology. BM response was graded as CR (required two time points to confirm), CR unconfirmed (one time point only), CR-MRD (bone marrow involvement < 5% at study entry with negative follow-up biopsies), SD, or PD. Patients with at least SD or better underwent central review of MIBG scans, CT scans, and bone marrow pathology slides. Overall responses of CR, CR-MRD, or PR were considered objective responses.

Outcome measures

Measure	Phase I n=19 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD Complete Response (CR)	0 Participants	—	—	—	—	—
Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD Partial Response (PR)	4 Participants	—	—	—	—	—
Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD Stable Disease	8 Participants	—	—	—	—	—
Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD Progressive Disease	5 Participants	—	—	—	—	—
Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD Response Rate (CR + CR-MRD + PR)	4 Participants	—	—	—	—	—
Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD CR-Minimal Residual Disease (MRD)	0 Participants	—	—	—	—	—
Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD Minor Response	2 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).

Population: Consisting of patients treated on the Phase 1 (n = 22), Phase 2 (n = 20), and Oral Solution (n = 12) cohorts.

To explore whether MYCN status and markers of expression of Aurora A in archival tumor tissue are associated with the antitumor activity of the combination of MLN8237, irinotecan, and temozolomide

Outcome measures

Measure	Phase I n=12 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=42 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Aurora A Expression MYCN Amplified	1 participants	14 participants	—	—	—	—
Aurora A Expression MYCN not Amplified	9 participants	24 participants	—	—	—	—
Aurora A Expression MYCN Missing	2 participants	4 participants	—	—	—	—
Aurora A Expression MYCN Amplified or Myc Positive	2 participants	16 participants	—	—	—	—
Aurora A Expression MYCN Non-amplified and Myc Negative	5 participants	11 participants	—	—	—	—
Aurora A Expression MYCN or Myc Missing	5 participants	15 participants	—	—	—	—
Aurora A Expression Aurora A protein Positive	2 participants	10 participants	—	—	—	—
Aurora A Expression Aurora A protein Negative	4 participants	14 participants	—	—	—	—
Aurora A Expression Aurora A protein Missing	6 participants	18 participants	—	—	—	—

SECONDARY outcome

Timeframe: Day 7 of cycle 1

Population: Consisting of patients treated on the Phase 1 (n = 22), Phase 2 (n = 20), and Oral Solution (n = 12) cohorts.

To explore whether UGT1A1 genotype is associated with toxicity in children with refractory neuroblastoma treated with the combination of MLN8237, irinotecan, and temozolomide

Outcome measures

Measure	Phase I n=11 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=43 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=27 Participants alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=27 Participants alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
UGT1A1 Genotype UGT1A1 6\6	2 participants	15 participants	8 participants	9 participants	—	—
UGT1A1 Genotype UGT1A1 6\7	3 participants	14 participants	6 participants	11 participants	—	—
UGT1A1 Genotype UGT1A1 7\7	3 participants	2 participants	4 participants	1 participants	—	—
UGT1A1 Genotype UGT1A1 Missing	3 participants	12 participants	9 participants	6 participants	—	—

SECONDARY outcome

Timeframe: Day 7 of cycle 1

Population: Consisting of patients treated on the Phase 1 (n = 22), Phase 2 (n = 20), and Oral Solution (n = 12) cohorts.

To explore whether AURKA genotype is associated with antitumor activity in children with refractory neuroblastoma treated with the combination of MLN8237, irinotecan, and temozolomide.

Outcome measures

Measure	Phase I n=12 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B n=42 Participants alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
AURKA Genotype AurkA Codon 31 Summary Missing	4 participants	10 participants	—	—	—	—
AURKA Genotype AurkA Codon 57 Summary H	3 participants	10 participants	—	—	—	—
AURKA Genotype AurkA Codon 57 Summary W	5 participants	22 participants	—	—	—	—
AURKA Genotype AurkA Codon 31 Summary H	3 participants	9 participants	—	—	—	—
AURKA Genotype AurkA Codon 31 Summary V	0 participants	1 participants	—	—	—	—
AURKA Genotype AurkA Codon 31 Summary W	5 participants	22 participants	—	—	—	—
AURKA Genotype AurkA Codon 57 Summary Missing	4 participants	10 participants	—	—	—	—

SECONDARY outcome

Timeframe: 1 Years after completion of study

Population: The analysis was performed in phase II patients.

To determine the progression free survival rates for patients with relapsed or refractory neuroblastoma treated with MLN8237, irinotecan, and temozolomide at the identified MTD

Outcome measures

Measure	Phase I n=20 Participants Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m\^2 per day on days 1 to 7 along with irinotecan 50 mg/m\^2 intravenously and temozolomide 100 mg/m\^2 orally on days 1 to 5.	DL 1B alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
One Year Progression Free Survival Rate	4 Participants	—	—	—	—	—

Adverse Events

DL 1

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

DL 1B

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

DL 2B

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

DL 3B

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Ph 2

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Oral Solution

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	DL 1 n=6 participants at risk alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis optional	DL 1B n=6 participants at risk alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 participants at risk alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 participants at risk alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Ph 2 n=20 participants at risk alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=12 participants at risk alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Diarrhea	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Mucositis oral	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Oral pain	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Vomiting	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Catheter related infection	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Infections and infestations - Other, specify	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Neutrophil count decreased	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Anorexia	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Dehydration	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Movements involuntary	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Pharyngeal mucositis	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).

Other adverse events

Measure	DL 1 n=6 participants at risk alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis optional	DL 1B n=6 participants at risk alisertib tablets (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 2B n=6 participants at risk alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	DL 3B n=4 participants at risk alisertib tablets (80 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Ph 2 n=20 participants at risk alisertib tablets (60 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required	Oral Solution n=12 participants at risk alisertib oral solution (45 mg/m\^2/dose x 7 days), irinotecan (50 mg/m\^2/dose IV x 5 days), temozolomide (100 mg/m\^2/dose orally x 5 days), myeloid growth factor support and cephalosporin diarrhea prophylaxis required
Renal and urinary disorders Proteinuria	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 23 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Renal and urinary disorders Urinary retention	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Renal and urinary disorders Urinary tract pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Renal and urinary disorders Urine discoloration	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Reproductive system and breast disorders Penile pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	16.7% 1/6 • Number of events 8 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 8 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 13 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 14 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Apnea	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Cough	83.3% 5/6 • Number of events 10 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 13 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 29 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 3/4 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	35.0% 7/20 • Number of events 14 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	41.7% 5/12 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 5/20 • Number of events 16 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Nasal congestion	50.0% 3/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 10 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	30.0% 6/20 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Pharyngeal mucositis	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Postnasal drip	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 22 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Respiratory, thoracic and mediastinal disorders Sore throat	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	20.0% 4/20 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Alopecia	50.0% 3/6 • Number of events 38 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 52 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	40.0% 8/20 • Number of events 86 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 4/12 • Number of events 32 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Bullous dermatitis	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Dry skin	16.7% 1/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 8 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 18 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Pruritus	33.3% 2/6 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 4/12 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Blood and lymphatic system disorders Anemia	100.0% 6/6 • Number of events 50 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 61 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 100 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 4/4 • Number of events 17 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	95.0% 19/20 • Number of events 147 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 10/12 • Number of events 41 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 2/12 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Blood and lymphatic system disorders Hemolysis	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Cardiac disorders Palpitations	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Cardiac disorders Sinus tachycardia	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 22 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	20.0% 4/20 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Ear and labyrinth disorders Ear pain	33.3% 2/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Endocrine disorders Hypothyroidism	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 14 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Eye disorders Blurred vision	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 13 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Eye disorders Conjunctivitis	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Eye disorders Dry eye	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Eye disorders Eye disorders - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Eye disorders Eye pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Eye disorders Photophobia	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Abdominal distension	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Abdominal pain	66.7% 4/6 • Number of events 17 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 8 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 10/20 • Number of events 17 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 4/12 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Anal pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Colitis	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Constipation	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 2/12 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Dental caries	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Diarrhea	100.0% 6/6 • Number of events 45 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 27 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 50 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 4/4 • Number of events 14 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	90.0% 18/20 • Number of events 88 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 9/12 • Number of events 27 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Dry mouth	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Dyspepsia	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Enterocolitis	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Flatulence	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 2/12 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Mucositis oral	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 4/6 • Number of events 18 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 5/20 • Number of events 11 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Nausea	100.0% 6/6 • Number of events 33 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 37 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 52 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 4/4 • Number of events 11 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	90.0% 18/20 • Number of events 98 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 9/12 • Number of events 17 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Oral dysesthesia	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Oral hemorrhage	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Oral pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Rectal hemorrhage	16.7% 1/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Rectal pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Stomach pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Toothache	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Gastrointestinal disorders Vomiting	66.7% 4/6 • Number of events 29 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 38 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 34 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 4/4 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	85.0% 17/20 • Number of events 68 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	91.7% 11/12 • Number of events 24 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Chills	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Edema face	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Edema trunk	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Facial pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Fatigue	66.7% 4/6 • Number of events 10 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 24 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 3/4 • Number of events 12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 10/20 • Number of events 23 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 4/12 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Fever	83.3% 5/6 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 10 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 10/20 • Number of events 15 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 4/12 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders General disorders and administration site conditions - Other, specify	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Infusion related reaction	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Infusion site extravasation	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Irritability	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 3/12 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Malaise	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Non-cardiac chest pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
General disorders Pain	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 2/12 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Conjunctivitis infective	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Enterocolitis infectious	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Infections and infestations - Other, specify	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Lung infection	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Mucosal infection	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Otitis externa	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Otitis media	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Rhinitis infective	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Sepsis	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Skin infection	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Upper respiratory infection	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 8 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	30.0% 6/20 • Number of events 8 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Urinary tract infection	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Infections and infestations Vaginal infection	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Injury, poisoning and procedural complications Bruising	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	20.0% 4/20 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Injury, poisoning and procedural complications Burn	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Injury, poisoning and procedural complications Fall	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Injury, poisoning and procedural complications Vascular access complication	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Activated partial thromboplastin time prolonged	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Alanine aminotransferase increased	100.0% 6/6 • Number of events 36 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 4/6 • Number of events 32 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 51 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 3/4 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	90.0% 18/20 • Number of events 112 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 8/12 • Number of events 23 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Alkaline phosphatase increased	33.3% 2/6 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	35.0% 7/20 • Number of events 32 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Aspartate aminotransferase increased	100.0% 6/6 • Number of events 42 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 4/6 • Number of events 23 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 51 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	85.0% 17/20 • Number of events 103 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 10/12 • Number of events 22 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Blood bilirubin increased	33.3% 2/6 • Number of events 17 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 11 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Creatinine increased	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 27 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 5/20 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 3/12 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations GGT increased	50.0% 3/6 • Number of events 12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 32 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Hemoglobin increased	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Investigations - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Lymphocyte count decreased	50.0% 3/6 • Number of events 32 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 4/6 • Number of events 21 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 43 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 3/4 • Number of events 14 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	85.0% 17/20 • Number of events 111 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 10/12 • Number of events 26 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Lymphocyte count increased	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 8 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Neutrophil count decreased	100.0% 6/6 • Number of events 43 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 46 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 66 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 4/4 • Number of events 15 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 20/20 • Number of events 132 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 12/12 • Number of events 41 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Platelet count decreased	83.3% 5/6 • Number of events 43 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 55 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 93 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 4/4 • Number of events 16 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 20/20 • Number of events 154 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 10/12 • Number of events 43 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Weight gain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 25 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations Weight loss	33.3% 2/6 • Number of events 22 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 13 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 3/4 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	41.7% 5/12 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Investigations White blood cell decreased	100.0% 6/6 • Number of events 55 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 57 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 6/6 • Number of events 89 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 3/4 • Number of events 15 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 20/20 • Number of events 150 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	91.7% 11/12 • Number of events 45 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Acidosis	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Anorexia	50.0% 3/6 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 4/6 • Number of events 40 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	100.0% 4/4 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 10/20 • Number of events 25 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	41.7% 5/12 • Number of events 17 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Dehydration	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 4/6 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	30.0% 6/20 • Number of events 10 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 2/12 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hyperglycemia	66.7% 4/6 • Number of events 11 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 4/6 • Number of events 22 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	45.0% 9/20 • Number of events 27 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	41.7% 5/12 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hyperkalemia	16.7% 1/6 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 17 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 3/12 • Number of events 11 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypernatremia	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 10 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 3/12 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypertriglyceridemia	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypoalbuminemia	66.7% 4/6 • Number of events 18 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 18 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	55.0% 11/20 • Number of events 19 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 8/12 • Number of events 14 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypocalcemia	50.0% 3/6 • Number of events 27 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 29 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	55.0% 11/20 • Number of events 22 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	41.7% 5/12 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypoglycemia	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 13 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypokalemia	66.7% 4/6 • Number of events 29 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 4/6 • Number of events 14 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 3/4 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 10/20 • Number of events 26 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 6/12 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypomagnesemia	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 10 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 5/20 • Number of events 10 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 4/12 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hyponatremia	66.7% 4/6 • Number of events 11 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 10 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	83.3% 5/6 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	40.0% 8/20 • Number of events 12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 6/12 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Hypophosphatemia	50.0% 3/6 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	40.0% 8/20 • Number of events 11 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 6/12 • Number of events 15 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Musculoskeletal and connective tissue disorders Back pain	33.3% 2/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	66.7% 4/6 • Number of events 25 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	20.0% 4/20 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 3/12 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Depressed level of consciousness	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Dizziness	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	20.0% 4/20 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 2/12 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Dysgeusia	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Headache	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 3/6 • Number of events 11 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	75.0% 3/4 • Number of events 6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	45.0% 9/20 • Number of events 18 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Nervous system disorders - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Paresthesia	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Peripheral motor neuropathy	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Presyncope	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Somnolence	16.7% 1/6 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	20.0% 4/20 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 3/12 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Syncope	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Nervous system disorders Tremor	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Psychiatric disorders Agitation	16.7% 1/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 8 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 2/12 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Psychiatric disorders Anxiety	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 5 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 9 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Psychiatric disorders Depression	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Psychiatric disorders Hallucinations	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Psychiatric disorders Insomnia	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Psychiatric disorders Psychiatric disorders - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Psychiatric disorders Restlessness	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Renal and urinary disorders Acute kidney injury	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Renal and urinary disorders Hematuria	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 24 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 2/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	15.0% 3/20 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 2/12 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	33.3% 2/6 • Number of events 11 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 2/12 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Skin and subcutaneous tissue disorders Urticaria	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Surgical and medical procedures Surgical and medical procedures - Other, specify	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/20 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Vascular disorders Flushing	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Vascular disorders Hematoma	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Vascular disorders Hypertension	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	50.0% 2/4 • Number of events 3 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	5.0% 1/20 • Number of events 4 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	0.00% 0/12 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
Vascular disorders Hypotension	0.00% 0/6 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	16.7% 1/6 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	25.0% 1/4 • Number of events 2 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	10.0% 2/20 • Number of events 7 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).	8.3% 1/12 • Number of events 1 • From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).

Additional Information

NANT Medical Director

New Approaches to Neuroblastoma Therapy

Phone: 323-361-5687

Email: nantops@chla.usc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place