Trial Outcomes & Findings for Phase 2 Study of Study of Tesevatinib in Subjects With NSCLC and Brain or Leptomeningeal Metastases (NCT NCT02616393)

Last Updated: 2022-03-16

Results Overview

The best overall response rates (ORRs) of subjects who had brain tumors and exhibited either a complete response (CR) or a partial responder (PR) to therapy divided by the total number of subjects treated with tesevatinib 300 mg PO QD. Response rates are in accordance with RECIST Version 1.1 criteria. Since such brain metastases (BM) tumors can either affect the central nervous system (CNS) or not affect the CNS (non-CNS), they were categorized into CNS and non-CNS subsets. Because leptomeningeal metastases (LM) only are considered cancer cell migration from the breast, lung, or some other part of the body to the cerebrospinal fluid (CSF), analysis of CNS are not appropriate, so Cohort B is excluded.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first

Results posted on

2022-03-16

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A (BM) Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort B (LM) Subjects with leptomeningeal metastases (LM) who received tesevatinib 300 mg PO QD	Cohort C (BM-IP) Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD
Overall Study STARTED	13	20	3
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	13	20	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A (BM) Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort B (LM) Subjects with leptomeningeal metastases (LM) who received tesevatinib 300 mg PO QD	Cohort C (BM-IP) Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD
Overall Study Death	5	12	1
Overall Study Termination by Sponsor	4	5	2
Overall Study Other	3	0	0
Overall Study Withdrawal by Subject	1	1	0
Overall Study Lost to Follow-up	0	2	0

Baseline Characteristics

Phase 2 Study of Study of Tesevatinib in Subjects With NSCLC and Brain or Leptomeningeal Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A - Brain Metastases n=13 Participants Tesevatinib will be orally administered with a dose of 300 mg once daily to subjects with NSCLC who have progressed with BM Tesevatinib	Cohort B - Leptomeningeal Metastases n=20 Participants Tesevatinib will be orally administered with a dose of 300 mg once daily to subjects with NSCLC who have progressed with LM Tesevatinib	Cohort C - Brain Metastases at Initial Presentation n=3 Participants Tesevatinib will be orally administered with a dose of 300 mg once daily to subjects with NSCLC with BM at initial presentation Tesevatinib	Total n=36 Participants Total of all reporting groups
Age, Continuous	60.7 years n=5 Participants	56.3 years n=7 Participants	64.7 years n=5 Participants	58.6 years n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	15 Participants n=7 Participants	2 Participants n=5 Participants	23 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	19 Participants n=7 Participants	3 Participants n=5 Participants	32 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	10 Participants n=7 Participants	0 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	8 Participants n=7 Participants	1 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
EORTC-QLQ-C30 Questionnaire	59.2 Units (score) on a scale STANDARD_DEVIATION 20.48 • n=5 Participants	66.5 Units (score) on a scale STANDARD_DEVIATION 12.84 • n=7 Participants	51.7 Units (score) on a scale STANDARD_DEVIATION 5.51 • n=5 Participants	62.7 Units (score) on a scale STANDARD_DEVIATION 60.6 • n=4 Participants
EORTC-QLQ-BN20 Questionnaire	34.0 Units (score) on a scale STANDARD_DEVIATION 15.71 • n=5 Participants	37.7 Units (score) on a scale STANDARD_DEVIATION 8.64 • n=7 Participants	22.0 Units (score) on a scale STANDARD_DEVIATION 2.00 • n=5 Participants	35.1 Units (score) on a scale STANDARD_DEVIATION 11.89 • n=4 Participants

PRIMARY outcome

Timeframe: Until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first

Population: Subjects with BM only (Cohorts A and C). Subjects with LM (Cohort B) were excluded.

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=13 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) n=3 Participants Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM n=16 Participants All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Best Overall Response Rate (ORR) of Subjects With BM CNS	15.4 Percentage of participants (%) Interval 2.0 to 45.0	100 Percentage of participants (%) Interval 29.0 to 100.0	31.3 Percentage of participants (%) Interval 11.0 to 59.0	—
Best Overall Response Rate (ORR) of Subjects With BM non-CNS	0 Percentage of participants (%) Interval 0.0 to 25.0	100 Percentage of participants (%) Interval 29.0 to 100.0	18.8 Percentage of participants (%) Interval 4.0 to 46.0	—
Best Overall Response Rate (ORR) of Subjects With BM CNS + non-CNS	15.4 Percentage of participants (%) Interval 2.0 to 45.0	100 Percentage of participants (%) Interval 29.0 to 100.0	31.3 Percentage of participants (%) Interval 11.0 to 59.0	—

PRIMARY outcome

Timeframe: Until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first

The best overall response rates (ORRs) of subjects who had leptomeningeal tumors and exhibited either a complete response (CR) or a partial responder (PR) to therapy divided by the total number of subjects treated with tesevatinib 300 mg PO QD. Response rates are in accordance with RECIST Version 1.1 criteria. Since leptomeningeal metastases (LM) are only considered cancer cell migration from the breast, lung, or some other part of the body to the cerebrospinal fluid (CSF), analysis of CNS are not appropriate, so Cohorts A and C are excluded.

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=20 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Best ORR of Subjects With LM	0 Percentage of participants (%)	—	—	—

SECONDARY outcome

Timeframe: Until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first

Median duration of survival without progression of subjects treated with tesevatinib 300 mg PO QD.

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=13 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) n=20 Participants Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM n=3 Participants All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Median Progression-free Survival (PFS)	9.29 Weeks Interval 4.14 to 27.43	10.86 Weeks Interval 6.86 to 17.14	37.71 Weeks Interval 20.14 to 62.14	—

SECONDARY outcome

Timeframe: 24 weeks (6 months)

Population: Note: Cohort C (BM-IP) did not have a sufficient number of subjects with events to determine the PFS at 12 or 24 weeks.

Probability that subjects with brain metastases (BM) or leptomeningeal metastases (LM) would not progress, i.e., progression-free survival (PFS) after 12 weeks (3 months) and after 24 weeks (6 months) of treatment with tesevatinib 300 mg PO QD

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=13 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) n=20 Participants Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Probability of PFS at 12 Weeks and 24 Weeks--Cohort A (BM Only) and Cohort B (LM Only) 12 weeks (3 months)	0.4762 Probability Interval 0.1823 to 0.7237	0.4737 Probability Interval 0.2444 to 0.6728	—	—
Probability of PFS at 12 Weeks and 24 Weeks--Cohort A (BM Only) and Cohort B (LM Only) 24 weeks (6 months)	0.2857 Probability Interval 0.0698 to 0.5546	0.2632 Probability Interval 0.0958 to 0.4677	—	—

SECONDARY outcome

Timeframe: 24 weeks (6 months)

Population: Note: Insufficient data for PFS probability at 12 weeks

Probability that subjects with brain metastases at initial presentation (BM-IP) would not progress, i.e., progression-free survival (PFS) after 24 weeks (6 months) of treatment with tesevatinib 300 mg PO QD

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=3 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Probability of PFS at 24 Weeks--Cohort C (BM-IP Only)	0.6667 Probability Interval 0.0541 to 0.9452	—	—	—

SECONDARY outcome

Timeframe: 24 weeks (6 months)

Population: Note: Cohort C did not have a sufficient number of subjects with events to determine the probability of survival at 12 or 24 weeks.

Probability that subjects with brain metastases (BM) or leptomeningeal metastases (LM) survived (overall survival \[OS\]) after 12 weeks (3 months) and after 24 weeks (6 months) of treatment with tesevatinib 300 mg PO QD

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=13 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) n=20 Participants Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Probability of OS at 12 Weeks and at 24 Weeks--Cohort A (BM Only) and Cohort B (LM Only) 12 weeks (3 months)	0.8462 Probability Interval 0.5122 to 0.9591	0.8471 Probability Interval 0.5968 to 0.948	—	—
Probability of OS at 12 Weeks and at 24 Weeks--Cohort A (BM Only) and Cohort B (LM Only) 24 weeks (6 months)	0.7692 Probability Interval 0.4421 to 0.9191	0.6353 Probability Interval 0.3831 to 0.807	—	—

SECONDARY outcome

Timeframe: Until disease progression, death, unacceptable toxicity, or up to 2 years, whichever occurred first

Median time to the development of disease progression (TTP) for subjects in Cohort A, Cohort B and Cohort C who were treated with tesevatinib 300 mg PO QD

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=13 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) n=20 Participants Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM n=3 Participants All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Median Time to Progression (TTP)--Cohort A (BM), Cohort B (LM), Cohort C (BM-IP)	21.43 Weeks Interval 4.14 to 27.43	8.14 Weeks Interval 6.0 to 35.86	34.93 Weeks Interval 32.14 to 37.71	—

SECONDARY outcome

Timeframe: 24 weeks (6 months)

Population: Note: Cohort C (BM-IP) did not have a sufficient number of subjects with events to determine the probability of TTP at 12 weeks or 24 weeks.

Probability that the time to progression (TTP) for subjects with no metastases to the central nervous system (non-CNS) in Cohort A (brain metastases only) or Cohort B (leptomeningeal metastases only) would be at 12 weeks (3 months) and at 24 weeks (6 months) of therapy with tesevatinib 300 mg PO QD. There were an insufficient number of subjects in Cohort C (brain metastases at initial presentation) who had events.

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=13 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) n=20 Participants Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Probability of TTP at 12 Weeks and 24 Weeks--Non-CNS Cohort A (BM Only) and Cohort B (LM Only) Non-CNS at 12 weeks	0.5625 Probability Interval 0.1468 to 0.8415	0.4396 Probability Interval 0.1684 to 0.6844	—	—
Probability of TTP at 12 Weeks and 24 Weeks--Non-CNS Cohort A (BM Only) and Cohort B (LM Only) Non-CNS at 24 weeks	0.2813 Probability Interval 0.0135 to 0.688	0.2637 Probability Interval 0.065 to 0.5521	—	—

SECONDARY outcome

Timeframe: 24 weeks (6 months)

Probability that the time to progression (TTP) for subjects with metastases to the central nervous system (CNS) would be at 24 weeks (6 months) of therapy with tesevatinib 300 mg PO QD.

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=13 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) n=20 Participants Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM n=3 Participants All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Probability of TTP at 24 Weeks--CNS	0.3636 Probability Interval 0.0584 to 0.6976	0.4795 Probability Interval 0.1541 to 0.7491	0.5000 Probability Interval 0.006 to 0.9104	—

SECONDARY outcome

Timeframe: Until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first

Population: Note: Not all subjects were available for analysis at all visits.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Cancer 30 (C30) is a 30-question assessment composed of both multi-item scales and single-item measures: 5 functional scales, 3 symptom scales, 1 global QoL scale, and 6 single items. Ratings are on a 4-point scale (not at all, a little quite a bit, very much), with scoring from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems. The outcome measure is the mean change in the EORTC-QLQ-C30 from baseline to a visit.

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=13 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) n=20 Participants Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM n=3 Participants All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) n=36 Participants All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Quality of Life (QoL): Mean Change From Baseline in EORTC-QLQ-C30 Questionnaire Scores Baseline Score (35 subjects)	59.2 Score on a scale Standard Deviation 20.48	66.5 Score on a scale Standard Deviation 12.84	51.7 Score on a scale Standard Deviation 5.51	62.7 Score on a scale Standard Deviation 15.91
Quality of Life (QoL): Mean Change From Baseline in EORTC-QLQ-C30 Questionnaire Scores Mean Change--Cycle 3 Day 1 Change From Baseline	3.6 Score on a scale Standard Deviation 5.22	2.1 Score on a scale Standard Deviation 12.09	3.3 Score on a scale Standard Deviation 0.58	2.8 Score on a scale Standard Deviation 8.64
Quality of Life (QoL): Mean Change From Baseline in EORTC-QLQ-C30 Questionnaire Scores Mean Change from Baseline--Cycle 5 Day 1	2.8 Score on a scale Standard Deviation 4.21	5.5 Score on a scale Standard Deviation 10.61	1.0 Score on a scale Standard Deviation 5.00	2.8 Score on a scale Standard Deviation 5.35
Quality of Life (QoL): Mean Change From Baseline in EORTC-QLQ-C30 Questionnaire Scores Mean Change from Baseline to End-of-Study	2.9 Score on a scale Standard Deviation 5.17	7.2 Score on a scale Standard Deviation 14.34	15.0 Score on a scale Standard Deviation 4.00	6.7 Score on a scale Standard Deviation 10.74

SECONDARY outcome

Timeframe: Until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first

Population: Not all subjects were available for all analyses.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Cancer BN20 Questionnaire is a 20-question assessment of symptomatology based on a categorical scale (Not at all = 1; A little = 2; Quite a bit = 3; and Very much = 4). For 20 questions: minimum score = 20 and maximum score = 80. Higher scores indicate greater level of symptomatology/problems. The outcome measure is the mean change in the EORTC-QLQ-BN20 from baseline to a visit.

Outcome measures

Outcome measures
Measure	Cohort A (BM) n=13 Participants Subjects with brain metastases (BM) who received tesevatinib 300 mg orally (PO) once daily (QD)	Cohort C (BM-IP) n=20 Participants Subjects with brain metastases at initial presentation (BM-IP) who received tesevatinib 300 mg PO QD	Overall BM n=3 Participants All subjects with brain metastases who received tesevatinib 300 mg PO QD	All Subjects (Cohorts A+B+C) n=36 Participants All subjects with BM, LM or BM-IP who were administered tesevatinib 300 mg PO QD
Quality of Life (QoL): Mean Change From Baseline in EORTC-QLQ-BN20 Questionnaire Scores Baseline Score (35 subjects)	34.0 Score on a scale Standard Deviation 15.71	37.7 Score on a scale Standard Deviation 8.64	22.0 Score on a scale Standard Deviation 2.00	35.1 Score on a scale Standard Deviation 11.89
Quality of Life (QoL): Mean Change From Baseline in EORTC-QLQ-BN20 Questionnaire Scores Mean Change from Baseline--Cycle 3 Day 1 Change From Baseline	0.3 Score on a scale Standard Deviation 4.89	1.9 Score on a scale Standard Deviation 6.66	3.7 Score on a scale Standard Deviation 2.08	1.6 Score on a scale Standard Deviation 5.44
Quality of Life (QoL): Mean Change From Baseline in EORTC-QLQ-BN20 Questionnaire Scores Mean Change from Baseline--Cycle 5 Day 1 Change From Baseline	-4.0 Score on a scale Standard Deviation 5.34	2.5 Score on a scale Standard Deviation 12.02	8.7 Score on a scale Standard Deviation 8.96	1.1 Score on a scale Standard Deviation 8.97
Quality of Life (QoL): Mean Change From Baseline in EORTC-QLQ-BN20 Questionnaire Scores Mean Change from Baseline to End-of-Study	2.6 Score on a scale Standard Deviation 3.05	7.3 Score on a scale Standard Deviation 12.35	12.3 Score on a scale Standard Deviation 10.26	6.4 Score on a scale Standard Deviation 9.73

Adverse Events

Cohort A - Brain Metastases

Serious events: 6 serious events

Other events: 13 other events

Deaths: 5 deaths

Cohort B - Leptomeningeal Metastases

Serious events: 13 serious events

Other events: 20 other events

Deaths: 12 deaths

Cohort C - Brain Metastases at Initial Presentation

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

All Subjects (Cohorts A+B+C)

Serious events: 21 serious events

Other events: 36 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

Miranda Ross

Kadmon Corporation

Phone: 724-778-6170

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort A - Brain Metastases n=13 participants at risk Tesevatinib 300 mg administered orally (PO) once daily (QD) to subjects with NSCLC who have progressed with BM	Cohort B - Leptomeningeal Metastases n=20 participants at risk Tesevatinib 300 mg administered PO to subjects with NSCLC who have progressed with LM	Cohort C - Brain Metastases at Initial Presentation n=3 participants at risk Tesevatinib 300 mg administered PO to subjects with NSCLC who presented initially with brain metastases	All Subjects (Cohorts A+B+C) n=36 participants at risk Tesevatinib 300 mg administered PO to all subjects with NSCLC who had brain metastases and who had leptomeningeal metastases
Infections and infestations Urinary tract infection	7.7% 1/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	10.0% 2/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	8.3% 3/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Renal and urinary disorders Acute kidney injury	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	10.0% 2/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.6% 2/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Metabolism and nutrition disorders Dehydration	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	10.0% 2/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.6% 2/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Nervous system disorders Encephalopathy	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	10.0% 2/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.6% 2/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Metabolism and nutrition disorders Failure to thrive	7.7% 1/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.6% 2/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Musculoskeletal and connective tissue disorders Muscular weakness	7.7% 1/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.6% 2/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Gastrointestinal disorders Abdominal pain	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	33.3% 1/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Psychiatric disorders Confusional state	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
General disorders Disease progression	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	33.3% 1/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Nervous system disorders Dysarthria	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Gastrointestinal disorders Dysphagia	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Vascular disorders Embolism	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	33.3% 1/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Infections and infestations Enterocolitis infectious	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
General disorders Fatigue	7.7% 1/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
General disorders Gait disturbance	7.7% 1/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Nervous system disorders Headache	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Gastrointestinal disorders Nausea	7.7% 1/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Infections and infestations Pneumonia	7.7% 1/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	7.7% 1/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Respiratory, thoracic and mediastinal disorders Pneumonthorax	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Infections and infestations Postoperative wound infection	7.7% 1/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Nervous system disorders Seizure	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Infections and infestations Sepsis	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.
Injury, poisoning and procedural complications Subdural hematoma	0.00% 0/13 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	5.0% 1/20 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	0.00% 0/3 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.	2.8% 1/36 • Subjects were treated with tesevatinib 300 mg QD until disease progression, unacceptable toxicity, or up to 2 years, whichever occurred first.