Trial Outcomes & Findings for Cabozantinib-S-Malate and Erlotinib Hydrochloride in Treating Patients With Previously Treated Metastatic Non-Small Cell Lung Cancer (NCT NCT01866410)

NCT ID: NCT01866410

Last Updated: 2019-05-16

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: Up to 2 years
• Results posted on: 2019-05-16

Participant Flow

Participant milestones

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Overall Study STARTED	37
Overall Study COMPLETED	37
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cabozantinib-S-Malate and Erlotinib Hydrochloride in Treating Patients With Previously Treated Metastatic Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=37 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Age, Continuous	64 years n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Race/Ethnicity, Customized Asian	10 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian (non-Hispanic)	21 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	4 Participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	1 Participants n=5 Participants
Region of Enrollment United States	37 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Outcome measures

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=37 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Negative Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had negative T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Unknown Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had unknown T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Objective Response Rate	10.8 percentage of participants Interval 0.3 to 21.3	—	—

SECONDARY outcome

Timeframe: Up to 2 years

Tumor doubling time was estimated using an exponential growth model. Specifically, the pre-progression scan, and the baseline scan were used to estimate the doubling time prior to enrollment, td = log(2)∗1time/1log(tumor size) [derivation, S(t) = S(to)∗2∧[(t-to)/td] for a parameterization of exponential growth with a doubling time of td. Taking the logarithm on both sides: log(S(t))-log(S(to)) = log(2)∗(t - to)/td or td = log(2)∗(t - to)/[log(S(t))-log(S(to))] = log(2)∗1time/1log(S)], the baseline scan and first evaluation scan were used to determine the doubling time. Based on pre-planned protocol assessment, we estimated the percent of patients that experienced a slowing of tumor kinetics (a 30% increase in the length of time for tumor doubling) based on RECIST v1.1 measurements. Patients who did not get a scan on study, and patients whose pre-progression scans were missing or whose pre-progression tumor size was zero or whose tumor was decreasing prior to enrollment were excluded.

Outcome measures

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=34 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Negative Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had negative T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Unknown Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had unknown T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Percentage of Patients With a Greater Than 30% Increase in Tumor Doubling Time	79 percentage of participants Interval 62.0 to 91.0	—	—

SECONDARY outcome

Timeframe: Up to 2 years

Grade 3 & 4 adverse events attributed to treatment agents. Events are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Outcome measures

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=37 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Negative Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had negative T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Unknown Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had unknown T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Number of Adverse Events Alanine aminotransferase increased	1 Participants	—	—
Number of Adverse Events Aspartate aminotransferase increased	1 Participants	—	—
Number of Adverse Events Dehydration	2 Participants	—	—
Number of Adverse Events Diarrhea	12 Participants	—	—
Number of Adverse Events Fatigue	2 Participants	—	—
Number of Adverse Events Hypertension	1 Participants	—	—
Number of Adverse Events Hypokalemia	1 Participants	—	—
Number of Adverse Events Hypotension	1 Participants	—	—
Number of Adverse Events Lipase increased	4 Participants	—	—
Number of Adverse Events Lymphocyte count decreased	1 Participants	—	—
Number of Adverse Events Myalgia	1 Participants	—	—
Number of Adverse Events Nausea/Vomiting	3 Participants	—	—
Number of Adverse Events Neutrophil count decreased	1 Participants	—	—
Number of Adverse Events Rash acneiform	2 Participants	—	—
Number of Adverse Events Rash maculo-papular	2 Participants	—	—
Number of Adverse Events Serum amylase increased	4 Participants	—	—
Number of Adverse Events Thromboembolic event	1 Participants	—	—
Number of Adverse Events White blood cell decreased	1 Participants	—	—

SECONDARY outcome

Timeframe: Up to 2 years

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), ≥ 20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest diameter recorded or the appearance of one or more new lesions; Stable Disease (SD), Neither CR, PR or PD.

Outcome measures

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=37 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Negative Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had negative T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Unknown Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had unknown T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Best Response Patient Count Partial Response	4 Participants	—	—
Best Response Patient Count Stable Disease	21 Participants	—	—
Best Response Patient Count Progressive Disease	12 Participants	—	—

SECONDARY outcome

Timeframe: Until disease progression or death from any cause, up to 2 years

Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=37 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Negative Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had negative T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Unknown Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had unknown T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Progression-free Survival	3.6 months Interval 2.0 to 5.6	—	—

SECONDARY outcome

Timeframe: Until death from any cause, up to 2 years

Estimated using the product-limit method of Kaplan and Meier.

Outcome measures

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=37 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Negative Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had negative T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Unknown Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had unknown T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Overall Survival	13.3 months Interval 7.1 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Until disease progression or death from any cause, up to 2 years

Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. DNA was analyzed for the presence of the T790M point mutation.

Outcome measures

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=18 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Negative n=13 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had negative T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Unknown n=6 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had unknown T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Progression-free Survival by T790M Mutation Status	2.3 months Interval 1.7 to 3.6	5.6 months Interval 2.8 to 7.3	2.4 months Interval 1.2 to 12.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Until death from any cause, up to 2 years

Estimated using the product-limit method of Kaplan and Meier.

Outcome measures

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=18 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Negative n=13 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had negative T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO	Cabozantinib-s-malate, Erlotinib Hydrochloride, T790M Unknown n=6 Participants Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients had unknown T790M status in tissue\\blood. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Overall Survival by T790M Mutation Status	11.3 months Interval 5.6 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	21.2 months Interval 5.9 to 21.2	NA months Interval 5.2 to The upper limit of the 95% confidence interval and median was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 6 months after last study treatment

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 6 months after last study treatment

Outcome measures

Outcome data not reported

Adverse Events

Cabozantinib-s-malate, Erlotinib Hydrochloride

Serious events: 25 serious events

Other events: 37 other events

Deaths: 32 deaths

Serious adverse events

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=37 participants at risk Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Gastrointestinal disorders Abdominal pain	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	24.3% 9/37 • Number of events 10 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	8.1% 3/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Death NOS	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Hepatobiliary disorders Cholecystitis	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Hepatobiliary disorders bile duct obstruction	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alanine aminotransferase increased	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Aspartate aminotransferase increased	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Blood bilirubin increased	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lipase increased	10.8% 4/37 • Number of events 5 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lymphocyte count decreased	5.4% 2/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Serum amylase increased	10.8% 4/37 • Number of events 7 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations White blood cell decreased	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Dehydration	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypokalemia	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyponatremia	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Myalgia	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Syncope	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Vasovagal reaction	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Confusion	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash acneiform	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.4% 2/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypertension	8.1% 3/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypotension	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Thromboembolic event	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Other adverse events

Measure	Cabozantinib-s-malate, Erlotinib Hydrochloride n=37 participants at risk Patients will receive (A) XL184 (cabozantinib) at 40-mg p.o. daily plus erlotinib at 150-mg p.o. daily in 4-week cycles. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cabozantinib S-malate: Given PO Erlotinib Hydrochloride: Given PO
Blood and lymphatic system disorders Anemia	54.1% 20/37 • Number of events 52 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Palpitations	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Pericardial effusion	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Sinus bradycardia	5.4% 2/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Sinus tachycardia	5.4% 2/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Endocrine disorders Hypothyroidism	5.4% 2/37 • Number of events 10 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Endocrine disorders Low testosterone	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Blurred vision	5.4% 2/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Dry eye	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Glaucoma	2.7% 1/37 • Number of events 8 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders bilateral blepharitis	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders blepharitis	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal distension	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal pain	29.7% 11/37 • Number of events 23 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Anal pain	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Bloating	8.1% 3/37 • Number of events 6 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Burping	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Constipation	32.4% 12/37 • Number of events 26 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	89.2% 33/37 • Number of events 132 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dry mouth	16.2% 6/37 • Number of events 13 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dyspepsia	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dysphagia	8.1% 3/37 • Number of events 4 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Flatulence	13.5% 5/37 • Number of events 8 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastritis	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	8.1% 3/37 • Number of events 6 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Hemorrhoidal hemorrhage	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Hemorrhoids	10.8% 4/37 • Number of events 8 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Increased appetite	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Mucositis oral	16.2% 6/37 • Number of events 14 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	40.5% 15/37 • Number of events 32 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Oral hemorrhage	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Oral pain	8.1% 3/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Pancreatitis	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Rectal hemorrhage	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Stomach pain	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	27.0% 10/37 • Number of events 14 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders broken tooth	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Chest tightness	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Chills	5.4% 2/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Edema limbs	16.2% 6/37 • Number of events 9 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	81.1% 30/37 • Number of events 98 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Flu like symptoms	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Malaise	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Non-cardiac chest pain	27.0% 10/37 • Number of events 16 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Pain	5.4% 2/37 • Number of events 7 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Swellign in limbs	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders body aches	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Immune system disorders Allergic reaction	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Fungal & Skin infection	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Lip infection	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Otitis media	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Papulopustular rash	5.4% 2/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Paronychia	16.2% 6/37 • Number of events 15 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Pharyngitis	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Sinusitis	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Skin infection	13.5% 5/37 • Number of events 8 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Upper respiratory infection	8.1% 3/37 • Number of events 5 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Urinary tract infection	16.2% 6/37 • Number of events 10 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Injury, poisoning and procedural complications Bruising	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Activated partial thromboplastin time pr	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alanine aminotransferase increased	56.8% 21/37 • Number of events 64 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alkaline phosphatase increased	29.7% 11/37 • Number of events 19 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Aspartate aminotransferase increased	64.9% 24/37 • Number of events 85 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Blood bilirubin increased	35.1% 13/37 • Number of events 24 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations CD4 lymphocytes decreased	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Cardiac troponin I increased	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Cholesterol high	5.4% 2/37 • Number of events 10 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Creatinine increased	8.1% 3/37 • Number of events 4 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Electrocardiogram QT corrected interval	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations GGT increase	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations GGT increased	27.0% 10/37 • Number of events 27 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Hemoglobin increased	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations INR increased	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations LDH Increase	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations LDH Increased	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations LDH increase	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations LDH increased	8.1% 3/37 • Number of events 4 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lipase increased	27.0% 10/37 • Number of events 17 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lymphocyte count decreased	40.5% 15/37 • Number of events 36 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Neutrophil count decreased	16.2% 6/37 • Number of events 14 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Platelet count decreased	18.9% 7/37 • Number of events 14 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Serum amylase increased	43.2% 16/37 • Number of events 46 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Weight gain	8.1% 3/37 • Number of events 8 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Weight loss	43.2% 16/37 • Number of events 43 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations White blood cell decreased	29.7% 11/37 • Number of events 43 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations blood LDH increase	16.2% 6/37 • Number of events 9 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations blood lactate dehydrogenase increased	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Anorexia	56.8% 21/37 • Number of events 53 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Dehydration	10.8% 4/37 • Number of events 5 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyperglycemia	16.2% 6/37 • Number of events 11 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyperkalemia	10.8% 4/37 • Number of events 6 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypermagnesemia	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypernatremia	13.5% 5/37 • Number of events 7 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypoalbuminemia	37.8% 14/37 • Number of events 29 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypocalcemia	37.8% 14/37 • Number of events 27 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypoglycemia	24.3% 9/37 • Number of events 31 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypokalemia	27.0% 10/37 • Number of events 18 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypomagnesemia	21.6% 8/37 • Number of events 14 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyponatremia	32.4% 12/37 • Number of events 33 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypophosphatemia	13.5% 5/37 • Number of events 11 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Obesity	8.1% 3/37 • Number of events 7 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Arthralgia	8.1% 3/37 • Number of events 6 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Avascular necrosis	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Back pain	29.7% 11/37 • Number of events 20 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Bone pain	13.5% 5/37 • Number of events 8 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Chest wall pain	13.5% 5/37 • Number of events 7 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Flank pain	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Myalgia	27.0% 10/37 • Number of events 29 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Neck pain	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	18.9% 7/37 • Number of events 12 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Aphasia	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Ataxia	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Cold intolerance	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Concentration impairment	5.4% 2/37 • Number of events 4 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Dizziness	18.9% 7/37 • Number of events 13 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Dysesthesia	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Dysgeusia	29.7% 11/37 • Number of events 29 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Headache	29.7% 11/37 • Number of events 19 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Lethargy	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Memory impairment	5.4% 2/37 • Number of events 5 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Neuralgia	5.4% 2/37 • Number of events 6 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Paresthesia	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Peripheral sensory neuropathy	5.4% 2/37 • Number of events 4 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Vasovagal reaction	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders aphasia	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders sensitivity to light and heat	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Anxiety	10.8% 4/37 • Number of events 10 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Confusion	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Depression	8.1% 3/37 • Number of events 6 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Insomnia	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders BPH	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Hematuria	5.4% 2/37 • Number of events 5 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Proteinuria	18.9% 7/37 • Number of events 9 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders URINARY PROBLEMS	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary BPH problem	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary BPH problems	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary Problem BPH	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary Problem PPH	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary Problems BPH	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary frequency	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary retention	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary tract obstruction	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary tract pain	8.1% 3/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Reproductive system and breast disorders Vaginal inflammation	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	10.8% 4/37 • Number of events 6 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Cough	51.4% 19/37 • Number of events 43 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	45.9% 17/37 • Number of events 41 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Hiccups	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Hoarseness	10.8% 4/37 • Number of events 18 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.1% 3/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	13.5% 5/37 • Number of events 7 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Postnasal drip	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	10.8% 4/37 • Number of events 8 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Runny nose	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Scratchy voice	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Sore throat	5.4% 2/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Wheezing	13.5% 5/37 • Number of events 7 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Alopecia	5.4% 2/37 • Number of events 4 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Callus	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Cellulitis	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Cracked nail	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Dry skin	48.6% 18/37 • Number of events 62 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Facial Rash	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Finger tip/nail cracks	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Hirsutism	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Hypertrichosis	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Nail Chenges, NOS	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Nail discoloration	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndro	8.1% 3/37 • Number of events 7 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Periorbital edema	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Pruritus	18.9% 7/37 • Number of events 14 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash acneiform	21.6% 8/37 • Number of events 23 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	43.2% 16/37 • Number of events 59 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Skin ulceration	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders facial rash	5.4% 2/37 • Number of events 4 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders finger tip/nail cracks	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders fingertip/nail cracks	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders ingrown eyelash	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders mild rash	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders mild tenderness Callus on foot	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders peeling of hands	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders rash	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders rash erythema	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders right hand laceration	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders yeast like rash	2.7% 1/37 • Number of events 2 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders yeast-like rash	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypertension	43.2% 16/37 • Number of events 76 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypotension	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Superficial thrombophlebitis	2.7% 1/37 • Number of events 1 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Thromboembolic event	2.7% 1/37 • Number of events 3 • Adverse events were recorded and graded throughout the study and until 30 days following the last dose of treatment agent. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Additional Information

Paul Frankel, Ph.D.

City of Hope

Phone: 626-218-5265

Email: pfrankel@coh.org

Results disclosure agreements

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

Restriction type: LTE60