Trial Outcomes & Findings for Linsitinib or Topotecan Hydrochloride in Treating Patients With Relapsed Small Cell Lung Cancer (NCT NCT01533181)

Last Updated: 2016-01-14

Results Overview

PFS: Time from randomization to time of disease progression or death. PFS summarized with the Kaplan-Meier (K-M) method by two arms (experimental versus control). Confidence intervals for the median PFS and PFS rates at different time points to be constructed when appropriate.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2016-01-14

Participant Flow

Participants were enrolled at Moffitt Cancer Center and nine other institutions in the United States from July 3, 2012 through November 1, 2013.

Participant milestones

Participant milestones
Measure	Arm A: Topotecan Participants receive topotecan hydrochloride IV over 30 minutes or orally (PO) daily (QD) on days 1-5. Patients may crossover to Arm B at the time of progressive disease.	Arm B: OS-906 OS-906 (linsitinib) daily, continuously, every 3 weeks.
Overall Study STARTED	15	29
Overall Study COMPLETED	14	28
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Topotecan Participants receive topotecan hydrochloride IV over 30 minutes or orally (PO) daily (QD) on days 1-5. Patients may crossover to Arm B at the time of progressive disease.	Arm B: OS-906 OS-906 (linsitinib) daily, continuously, every 3 weeks.
Overall Study Disease progression pre-active treatment	0	1
Overall Study Patient withdrawal pre-active treatment	1	0

Baseline Characteristics

Linsitinib or Topotecan Hydrochloride in Treating Patients With Relapsed Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Topotecan n=15 Participants Participants receive topotecan hydrochloride IV over 30 minutes or orally (PO) daily (QD) on days 1-5. Patients may crossover to Arm B at the time of progressive disease.	Arm B: OS-906 n=29 Participants OS-906 (linsitinib) daily, continuously, every 3 weeks.	Total n=44 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	17 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants
Age, Continuous	64 years n=5 Participants	62 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	17 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	29 participants n=7 Participants	44 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Population: All participants who received treatment

Outcome measures

Outcome measures
Measure	Arm A: Topotecan n=14 Participants Participants receive topotecan hydrochloride IV over 30 minutes or orally (PO) daily (QD) on days 1-5. Patients may crossover to Arm B at the time of progressive disease.	Arm B: OS-906 n=28 Participants OS-906 (linsitinib) daily, continuously, every 3 weeks.
Median Progression Free Survival (PFS)	3 months Interval 1.5 to 3.6	1.2 months Interval 1.1 to 1.4

SECONDARY outcome

Timeframe: Up to 2 years

Population: All evaluable participants at time of analysis

DCR: Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) + Progressive Disease (PD). DCR summarized using both point estimates and exact confidence intervals based on the binomial distribution by arm.

Outcome measures

Outcome measures
Measure	Arm A: Topotecan n=12 Participants Participants receive topotecan hydrochloride IV over 30 minutes or orally (PO) daily (QD) on days 1-5. Patients may crossover to Arm B at the time of progressive disease.	Arm B: OS-906 n=25 Participants OS-906 (linsitinib) daily, continuously, every 3 weeks.
Disease Control Rate (DCR) Complete Response	0 participants	0 participants
Disease Control Rate (DCR) Partial Response	2 participants	0 participants
Disease Control Rate (DCR) Stable Disease	4 participants	1 participants
Disease Control Rate (DCR) Progressive Disease	6 participants	24 participants
Disease Control Rate (DCR) Disease Control Rate	6 participants	1 participants

SECONDARY outcome

Timeframe: 1 year, 6 months

Population: All participants who received treatment

Participants with Grade 3 and 4 toxicities, possibly/probably/definitely related to study drugs. Number of Participants is per Event Category. Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Outcome measures

Outcome measures
Measure	Arm A: Topotecan n=14 Participants Participants receive topotecan hydrochloride IV over 30 minutes or orally (PO) daily (QD) on days 1-5. Patients may crossover to Arm B at the time of progressive disease.	Arm B: OS-906 n=28 Participants OS-906 (linsitinib) daily, continuously, every 3 weeks.
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Thromboembolic event	1 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Anemia	1 participants	1 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Blood and lymphatic system disorders - Other	2 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Thrombotic thrombocytopenic purpura	1 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Diarrhea	1 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Esophagitis	1 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Pancreatitis	1 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Fatigue	1 participants	3 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Alanine aminotransferase increased	0 participants	2 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Investigations - Other	1 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Lymphocyte count decreased	2 participants	3 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Neutrophil count decreased	4 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Platelet count decreased	4 participants	2 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs White blood cell decreased	4 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Anorexia	0 participants	1 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Dehydration	2 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Hyperglycemia	0 participants	1 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Hypokalemia	1 participants	0 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Hyponatremia	0 participants	1 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Headache	0 participants	1 participants
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs Hypoxia	0 participants	1 participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: All participants who received treatment

OS: Time from study enrollment to death from any cause. OS summarized similarly to PFS utilizing the K-M method.

Outcome measures

Outcome measures
Measure	Arm A: Topotecan n=14 Participants Participants receive topotecan hydrochloride IV over 30 minutes or orally (PO) daily (QD) on days 1-5. Patients may crossover to Arm B at the time of progressive disease.	Arm B: OS-906 n=28 Participants OS-906 (linsitinib) daily, continuously, every 3 weeks.
Overall Survival (OS)	5.3 months Interval 2.2 to 7.6	3.4 months Interval 1.8 to 5.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to day 1 of course 3

To be assessed by the Wilcoxon rank sum test.

Outcome measures

Outcome data not reported

Adverse Events

Arm A: Topotocan

Serious events: 7 serious events

Other events: 12 other events

Deaths: 0 deaths

Arm B: OS-906

Serious events: 18 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Alberto Chiappori

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-2158

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Arm A: Topotocan n=14 participants at risk Participants receive topotecan hydrochloride IV over 30 minutes or orally (PO) daily (QD) on days 1-5. Patients may crossover to Arm B at the time of progressive disease.	Arm B: OS-906 n=28 participants at risk OS-906 (linsitinib) daily, continuously, every 3 weeks.
Investigations White blood cell decreased	14.3% 2/14 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Dehydration	14.3% 2/14 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hypokalemia	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hyponatremia	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Blood and lymphatic system disorders Anemia	14.3% 2/14 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, Pancytopenia	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Abdominal pain	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Diarrhea	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Esophagitis	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Nausea	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Pancreatitis	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Vomiting	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Death NOS	50.0% 7/14 • Number of events 7 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	42.9% 12/28 • Number of events 12 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Fever	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Non-cardiac chest pain	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Pain	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Infections and infestations Enterocolitis infectious	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Infections and infestations Infections and infestations - Other, Possible pneumonia per x-ray	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Infections and infestations Lung infection	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	10.7% 3/28 • Number of events 4 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Infections and infestations Urinary tract infection	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Injury, poisoning and procedural complications Fracture	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Investigations Alanine aminotransferase increased	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Investigations Aspartate aminotransferase increased	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Investigations Blood bilirubin increase	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Investigations Lymphocyte count decreased	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Investigations Neutrophil count decreased	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Investigations Platelet count decreased	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified - Other, Progressive disease	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	10.7% 3/28 • Number of events 3 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified - Other, Death	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	21.4% 6/28 • Number of events 6 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Nervous system disorders Headache	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Nervous system disorders Intracranial hemorrhage	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Nervous system disorders Lethargy	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Psychiatric disorders Confusion	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Renal and urinary disorders Acute kidney injury	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	10.7% 3/28 • Number of events 6 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.

Other adverse events
Measure	Arm A: Topotocan n=14 participants at risk Participants receive topotecan hydrochloride IV over 30 minutes or orally (PO) daily (QD) on days 1-5. Patients may crossover to Arm B at the time of progressive disease.	Arm B: OS-906 n=28 participants at risk OS-906 (linsitinib) daily, continuously, every 3 weeks.
General disorders Fatigue	57.1% 8/14 • Number of events 11 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	57.1% 16/28 • Number of events 18 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Pain	21.4% 3/14 • Number of events 3 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	21.4% 6/28 • Number of events 8 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Chills	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Fever	14.3% 2/14 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders General Disorders - Other	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Flu like symptoms	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Malaise	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Edema limbs	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Non-cardiac chest pain	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Edema trunk	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Facial pain	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Edema face	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
General disorders Gait disturbance	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Nausea	42.9% 6/14 • Number of events 7 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	46.4% 13/28 • Number of events 15 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Vomiting	42.9% 6/14 • Number of events 8 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	28.6% 8/28 • Number of events 10 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Constipation	35.7% 5/14 • Number of events 5 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	28.6% 8/28 • Number of events 9 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Diarrhea	21.4% 3/14 • Number of events 4 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	21.4% 6/28 • Number of events 8 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Dyspepsia	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Gastrointestinal disorders - Other	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	14.3% 4/28 • Number of events 4 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Abdominal pain	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	10.7% 3/28 • Number of events 3 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Mucositis oral	14.3% 2/14 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Dysphagia	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Gastroesophageal reflux disease	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Bloating	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Fecal incontinence	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Gastritis	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Oral hemorrhage	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Oral pain	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	3.6% 1/28 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Pancreatitis	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Gastrointestinal disorders Stomach pain	7.1% 1/14 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	0.00% 0/28 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Anorexia	50.0% 7/14 • Number of events 7 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	42.9% 12/28 • Number of events 13 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hyponatremia	14.3% 2/14 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	39.3% 11/28 • Number of events 19 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hyperglycemia	21.4% 3/14 • Number of events 3 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	28.6% 8/28 • Number of events 10 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hypoalbuminemia	28.6% 4/14 • Number of events 4 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	28.6% 8/28 • Number of events 14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Dehydration	28.6% 4/14 • Number of events 6 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	14.3% 4/28 • Number of events 4 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hypokalemia	14.3% 2/14 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	21.4% 6/28 • Number of events 9 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hypocalcemia	14.3% 2/14 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	17.9% 5/28 • Number of events 5 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hyperkalemia	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hypomagnesemia	7.1% 1/14 • Number of events 1 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 4 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/14 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.	7.1% 2/28 • Number of events 2 • 1 year, 6 months Adverse Events are reported for all participants who received treatment, regardless of causality. Grades 3, 4 and 5 are noted on the appropriate reported SAEs. Note: Causality for SAEs is addressed in the Secondary Outcome Measure area.