Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

XL647

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

Tesevatinib in combination with Trastuzumab: tesevatinib 150 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.

Tesevatinib in combination with Trastuzumab: tesevatinib 250 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.

Tesevatinib in combination with Trastuzumab: tesevatinib 300 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.

Tesevatinib in combination with Trastuzumab: tesevatinib 350 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.

Tesevatinib

Evaluate the safety and tolerability and determine the maximum tolerated dose (MTD) of the combination of tesevatinib and trastuzumab in subjects with HER2-positive metastatic breast cancer

This is a multicenter, Phase 1b/2a, multiple ascending-dose, open-label study designed to assess the safety, tolerability, and efficacy of tesevatinib (KD019) in combination with trastuzumab in subjects with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The study planned to include a Phase 2a expansion in which approximately 50 subjects would receive tesevatinib at the maximum tolerated dose (MTD) dose determined in Phase 1b.

The study employs a successive cohort dose-escalation designed to determine the MTD of tesevatinib in combination with trastuzumab. The MTD dose is defined as the dose level below in which : (a) 2 of 3 subjects (or 2 of 6 subjects if Grade ≥ 3 tesevatinib related treatment emergent adverse event \[TEAE\] experience in 1 of the first 3 subjects).

In the Phase 1b portion of the study, tesevatinib is to be administered orally (PO) to successive cohorts of subjects at 150 mg, 250 mg, 300 mg, 350 mg, and 400 mg once daily (QD).

The following 4 dossing cohorts are initiated during the study:

* Cohort 1: 150 mg tesevatinib PO QD
* Cohort 2: 250 mg tesevatinib PO QD
* Cohort 3: 300 mg tesevatinib PO QD
* Cohort 4: 350 mg tesevatinib PO QD

\[Note: the sponsor suspended the study before a cohort of subjects were enrolled at tesevatinib 400 mg PO QD.\]

Trastuzumab is administered intravenously (IV) at 8 mg/kg as an initial loading dose on Day 1 of Cycle 1, followed by 6 mg/kg IV every 3 weeks thereafter, beginning Day 1 of Cycle 2. Subjects entering the study already on trastuzumab are not to receive the initial loading dose and instead receive trastuzumab 6 mg/kg IV. The first doses of trastuzumab and tesevatinib are administered in the clinic on Study Day 1. Subsequent doses of tesevatinib are to be taken on an outpatient basis for the remainder of each 21-day cycle. During Cycle 1, subjects are to be returned to the clinic for weekly safety and tolerability assessments.

Tumor response, both in the central nervous system (CNS) and peripheral to the CNS, is to be assessed after the second cycle of treatment and then at the end of every 2 cycles of treatment thereafter. Subjects are to be treated until disease progression or the subject experienced unacceptable toxicity. Subjects who demonstrated tumor progression are to stop study drug and followed for survival. All subjects discontinuing tesevatinib therapy are to be followed for survival.

Safety assessments include adverse event monitoring, electrocardiograms (ECGs), laboratory testing, physical examinations, vital signs, and pregnancy testing.

An End-of-Treatment visit is to be conducted as soon as possible after the subject's last dose of study drug. This could occur at the visit when disease progression is diagnosed. Subjects are to be followed for disease progression and survival.

A follow-up visit planned for 30 days (± 5 days) after the last dose of study drug assessments is to include collection of AE (Adverse Event) and concomitant medication data. This visit could occur prior to 30 days if a new therapy is started within 30 days of last dose of study drug.

For long-term follow-up, subjects are to be contacted by telephone every 8 weeks to assess survival status and any subsequent anti-cancer treatment.

The duration of treatment for subjects with tesevatinib in combination with trastuzumab is planned until the subject experiences disease progression or unacceptable toxicity.

\[Note: Changes to the Planned Analysis: The study, planned to include a Phase 2a expansion in which approximately 50 subjects would have received tesevatinib at the MTD dose determined in Phase 1b, was terminated early. Although some patients had prolonged stable disease in the study, no clear treatment responses were observed. The sponsor decided to suspend the study while gathering additional data from other tesevatinib oncology studies. The study was subsequently terminated early because the sponsor stopped evaluations of tesevatinib as a treatment for HER2-positive metastatic breast cancer.\]

A phase 1b ascending dose-finding study for establishing the maximum tolerated dose (MTD) of tesevatinib (with trastuzumab).

Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer

A Phase 1b/2a Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer

Percentage of subjects with at least 1 treatment-emergent adverse event of Grade 3 or greater or relationship with tesevatinib. TEAE grading was by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) where Grade 3 is severe and Grade 4 is life-threatening. TEAEs were considered related to study drug if the investigator assessed them as possibly related, probably related, or related.

Percentage of subjects with at least 1 serious adverse event considered related to study drug. SAEs were considered related to tesevatinib drug if the investigator assessed them as possibly related, probably related, or related.

The mean of the maximum serum concentration (Cmax) for the combination of tesevatinib and trastuzumab after 1 cycle (Cycle 2 Day 1).

The median time of the maximum serum concentration (Tmax) for the combination of tesevatinib and trastuzumab after 1 cycle (Cycle 2 Day 1)

The mean area under the concentration-time curve during the period from 0 to a given time point 't' in the tesevatinib 150 mg QD, 250 mg QD, and 300 mg QD cohorts.

The mean of the arithmetic mean accumulation ratio (AR) of the maximum concentration of tesevatinib. The AR is defined as:

Cmax for Cycle 2 divided by Cmax of Cycle 1.

The mean of the arithmetic mean accumulation ratio (AR) of the area under the concentration-time curve from 0 to 24 hours. The AR is defined as:

AUC(0-24hr) for Cycle 2 divided by AUC(0-24hr) for Cycle 1.

Kadmon Corporation, LLC

The Medical Dictionary of Regulatory Activities Summary of Classifications and Preferred Terms was used to describe AEs.

The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE; Version 4.03) was used for grading toxicities. Serious adverse events included those with Grade 4, life-threatening.

Tesevatinib 150 mg orally administered once daily in combination with Trastuzumab IV 8 mg/kg initially then 6 mg/kg trastuzunab every 3 weeks

Arm 1: Tesevatinib 150 mg PO QD + Trastuzumab 8 mg/kg IV

Tesevatinib 250 mg orally administered once daily in combination with Trastuzumab IV 8 mg/kg initially then 6 mg/kg trastuzunab every 3 weeks

Arm 2: Tesevatinib 250 mg PO QD + Trastuzumab 8 mg/kg IV

Tesevatinib 300 mg orally administered once daily in combination with Trastuzumab IV 8 mg/kg initially then 6 mg/kg trastuzumab every 3 weeks

Arm 3: Tesevatinib 300 mg PO QD + Trastuzumab 8 mg/kg IV

Tesevatinib 350 mg orally administered once daily in combination with Trastuzumab IV 8 mg/kg initially then 6 mg/kg trastuzumab every 3 weeks

Arm 4: Tesevatinib 350 mg PO QD + Trastuzumab 8 mg/kg IV

Combination of subjects in Cohorts 1, 2, 3, and 4

All Patients

Tesevatinib 150 mg orally administered once daily in combination with Trastuzumab IV 8 mg/kg initially then 6 mg/kg trastuzumab every 3 weeks

Tesevatinib 250 mg orally administered once daily in combination with Trastuzumab IV 8 mg/kg initially then 6 mg/kg trastuzumab every 3 weeks

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Childbearing potential

All subjects entered into study (Safety Population)

Associate Vice President, Clinical Operations

Grade ≥ 3

Related to Tesevatinib

Grade ≥ 3 Related to Tesevatinib

Tesevatinib 300 mg orally administered once daily in combination with Trastuzumab IV 8 mg/kg then 6 mg/kg trastuzumab every 3 weeks

All subjects who received at least 1 dose of study drug

Safety and Tolerability: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) by Severity and/or Relationship to Tesevatinib

All subjects who received at last 1 dose of study drug

Safety and Tolerability: Percentage of Subjects With Serious Adverse Event (SAE) Related to Tesevatinib

Subjects who completed at least 1 cycle of study drug and had PK (pharmacokinetics) measurements performed on Cycle 2 Day 1. Stratified by tesevatinib dose level, not by initial 8 mg/kg trastuzumab dosing level, i.e., 150 mg tesevatinib PO (by mouth) QD(once daily) / 6 mg/kg trastuzumab IV every 3 weeks. Note: Subjects in Cohort 350 mg tesevatinib received only 8 mg/kg trastuzumab and so were not included in this analysis.

Pharmacokinetics (PK): Mean Serum Cmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab

Subjects who completed at least 1 cycle of study drug and had PK measurements performed on Cycle 2 Day 1. Stratified by tesevatinib dose level, not by initial 8 mg/kg trastuzumab dosing level, i.e., 150, 250, and 300 mg tesevatinib with 6 mg/kg trastuzumab. Note: Subjects in Cohort 350 mg tesevatinib received only 8 mg/kg trastuzumab and so were not included in this analysis.

Pharmacokinetics: Median Serum Tmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab

Subjects who completed at least 1 cycle of study drug and had PK measurements performed on Cycle 2 Day 1. Stratified by tesevatinib dose level, not by initial 8 mg/kg trastuzumab dosing level, i.e., 150, 250, and 300 mg tesevatinib with 6 mg/kg trastuzumab. Note: Subjects in Cohort 350 mg tesevatinib received 8 mg/kg trastuzumab and so were not included in this analysis.

Pharmacokinetics: Mean Serum AUC(0-t) (Area Under Curve) of Treatment With Tesevatinib + Trastuzumab

Subjects who completed at least 1 cycle of study drug and had PK measurements performed on Cycle 2 Day 1. Stratified by tesevatinib dose level, not by initial 8 mg/kg trastuzumab dosing level, i.e., 150, 250, and 300 mg tesevatinib with 6 mg/kg trastuzumab. Note: Subjects in Cohort 350 mg tesevatinib only received 8 mg/kg trastuzumab and so were not included in this analysis.

Pharmacokinetics: Mean AR Cmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab

Pharmacokinetics: Mean AR AUC(0-24hr) After 1 Cycle of Treatment With Tesevatinib + Trastuzumab

Overall Study

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Brain Neoplasms

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

The single arm design assessing progression-free survival at 6 months (PFS-6) in the overall population with the ability to detect a rate of 25% is appropriate as a preliminary test of activity in patients with glioblastoma. The sample size of this study is also designed to permit the comparison of results with EGFR amplified and non-amplified tumors, as well as EGFRvIII mutated versus wild-type. The sample size is adequate to characterize the safety profile in patients with glioblastoma.

This is a multicenter, Phase 2 study to assess the activity of tesevatinib in patients with recurrent glioblastoma.

This is a multicenter, Phase 2 study to assess the activity of tesevatinib in subjects (n = 40) with recurrent glioblastoma. This study will be conducted at up to 10 sites in the United States.

The availability of paraffin-embedded tumor sample diagnostic of glioblastoma is mandatory for entry into the study. Tumor samples will be evaluated for the EGFRvIII mutation and for EGFR gene amplification. Tissue from recurrent surgery is preferred, but tissue from initial surgery is sufficient for study entry. Baseline MRI is mandatory.

After completion of the screening assessments and confirmation of study eligibility by the Medical Monitor upon review of an inclusion package, tesevatinib will be orally administered to all patients at a dose of 300 mg once daily. A cycle will be considered as 28 days. Patients will be evaluated for efficacy according to the Response Assessment in Neuro-Oncology (RANO) criteria.

Patients who develop ≥ Grade 3 adverse event(s) considered by the investigator to be related to study drug will have study treatment interrupted until the drug-related toxicities have resolved to ≤ Grade 1. Once toxicities have resolved to ≤ Grade 1, the patient may resume study treatment at a reduced dose of 250 mg/day. No more than 1 dose reduction is permitted. Patients who require more than one dose reduction will have study drug discontinued and enter the Follow-up Period.

Patients for whom toxicity persists beyond 21 days despite dose interruption may resume study treatment only with permission from the responsible Medical Monitor.

If study treatment is withheld, the patient should be instructed not to make up the withheld doses.

Study treatment will continue until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. Assessments for disease response will occur at Week 4 and Week 8 and then every 8 weeks thereafter using the RANO criteria.

Upon treatment discontinuation, patients will be followed every 8 weeks for survival.

Tumor samples will be used for exploratory biomarker research including, but not limited to, evaluation of EGFRvIII expression by immunohistochemistry or real-time Polymerase Chain Reaction. An appropriate definition and cutoff for EGFRvIII\^pos tumors will be established, and outcome in this subpopulation will be evaluated in addition to the overall study population.

To characterize the safety and tolerability profile of tesevatinib, patients will be monitored throughout the study for adverse events (all grades), serious adverse events, and any adverse events requiring drug interruption or discontinuation. Patients will undergo safety evaluations, including physical examinations, Karnofsky Performance Status (KPS), vital sign measurements, hematology, serum chemistry, urinalysis and electrocardiogram.

Magnetic resonance imaging (MRI) will be used to evaluate the tumor at baseline. All MRIs taken on study patients will be submitted to the sponsor for possible retrospective analysis.

Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma

A Phase 2, Multicenter Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma

Proportion (%) of subjects who did not have progressive disease after treatment with tesevatinib at 6 months (PFS-6) after baseline

Median duration (months) of subjects who were progression-free of disease from baseline

Median proportion (%) of subjects who survived 9 months after baseline

Median duration (months) subjects survived from baseline until death

Best overall response that subjects had to treatment with tesevatinib: complete response (CR), partial response (PR), stable disease (SD), or non-response/progressive disease (PD)

Proportion (%) of subjects who had either a complete response (CR) or a partial response (PR) to treatment with tesevatinib

Mean total amount of tesevatinib (mg) subjects received during the study

Median amount of tesevatinib (mg) subjects received during the study

Mean number of 28-day cycles of treatment with tesevatinib subjects received during the study

Median number of 28-day cycles of treatment with tesevatinib subjects received during the study

Subjects with recurrent glioblastoma who had or did not have EGFR gene-amplified and/or EGFRvIII\^pos variant glioblastoma. Includes 24 subjects who had EGFR gene-amplified (Sub-population A, 11 subjects who had EGFRvIII\^pos and EGFR gene-amplified (Sub-population B which is a subset of Sub-population A) and 16 subjects who were in neither sub-population

Subjects with EGFR gene-amplified glioblastoma

Sub-population A

Subjects with EGFRvIII\^pos variant glioblastoma (Subset of Sub-population A)

Sub-population B

Subjects with recurrent glioblastoma who had or did not have EGFR gene-amplified glioblastoma and/or EGFRvIII\^pos variant

Total: All Subjects

All Subjects

All Subjects: With or without EGFR gene-amplified and/or EGFRvIII\^pos variant. Sub-population A: EGFR gene-amplified. Sub-population B: EGFRvIII\^pos variant (Subset of Sub-population A).

Age, Customized

Sub-population A (EGFRvIII^pos glioblastoma)

Sub-population

Karnofsky Performance Score: 50 = requires considerable assistance and frequent medical care; 60 - requires occasional assistance, but is able to care for most of his personal needs; 70 = cares for self but is unable to carry on normal activity or to do active work; 80 = normal activity with effort and some signs or symptoms of disease; 90 - able to carry on normal activity and minor signs of symptoms of disease; 100 = normal no complaints with no evidence of disease

Karnofsky Performance Status (KPS)

Low-grade astrocytoma (diffuse astrocytoma): usually an infiltrating tumor that grows relatively slowly and usually does not have well-defined borders

Prior Low Grade Astrocytoma Diagnosis

Months Since First Diagnosis of Glioblastoma: Mean

Months Since First Diagnosis of Glioblastoma: Median

Months Since Recurrent Diagnosis of Glioblastoma: Mean

Months Since Recurrent Diagnosis of Glioblastoma: Median

Number of Prior Systemic Therapy Regimens

Prior Surgery

Analysis is for Sub-populations A and B, and for total which includes subjects in both Sub-populations A and B, and neither sub-population.

Prior Radiotherapy--Site Irradiated

Best overall response to previous therapy

Response Criteria in Solid Tumors (RECIST): CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease;

Best Overall Response

Reason Therapy Ended

Corticosteroid Used at Baseline

All Subjects: With or without EGFR gene-amplified and/or EGFRvIII\^pos variant Sub-population A: With EGFR gene-amplified only Sub-population B: With EGFR gene-amplified + EGFRvIII\^pos variant (Subset of Sub-population A) Note: EGFR = epidermal growth factor receptor

Miranda Ross

Subjects with recurrent glioblastoma who had or did not have EGFR gene-amplified and/or EGFRvIII\^pos variant

Subjects with EGFR gene-amplified and EGFRvIII\^pos variant glioblastoma (Subset of Sub-population A)

Efficacy: Median Progression-free Survival (PFS) Rate at 6 Months (PFS-6)

Subjects with recurrent glioblastoma who had or did not have EGFR gene-amplified and/or EGFRvIII\^pos glioblastoma

Subjects with EGFR Gene-amplified Glioblastoma

Subjects with EGFR gene-amplified and EGFRvIII\^pos glioblastoma (Subset of Sub-population A)

Efficacy: Median PFS

Efficacy: Median Overall Survival Rate at 9 Months (OS-9)

Efficacy: Median OS

Note: NA = data not available; NE = not evaluable

Efficacy: Best Overall Response

Efficacy: Objective Response Rate (ORR)

Exposure to Tesevatinib: Overall Mean

Exposure to Tesevatinib: Overall Median

Exposure to Tesevatinib: Mean Number of Cycles

Exposure to Tesevatinib: Median Number of Cycles

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Lung Neoplasms

Carcinoma

Neoplasms, Second Primary

Meningeal Carcinomatosis

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Meningeal Neoplasms

Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

Tesevatinib 300 mg orally (PO) once daily (QD) administered to subjects with NSCLC who had progressed with brain metastases (BM)

Tesevatinib 300 mg PO QD administered to subjects with NSCLC who had progressed with leptomeningeal metastases (LM)

Tesevatinib 300 mg PO QD administered NSCLC who presented initially with BM at initial presentation

A study to assess the activity of tesevatinib in subjects with non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations who have disease progression with Brain Metastases (BM) or Leptomeningeal Metastases (LM) or who have either BM or LM at initial presentation (IP)

This was a multicenter, phase 2, open-label study to assess the activity of tesevatinib, in subjects with non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations, and brain metastases (BM) or leptomeningeal metastases (LM).

After completion of the screening assessments and confirmation of study eligibility, tesevatinib was orally administered to all subjects at a dose of 300 mg once daily (QD). Tumor response, both in the central nervous system (CNS) and outside the central nervous system (non-CNS), was assessed after the second cycle of treatment and then at the end of every two cycles of treatment thereafter. Subjects were treated with tesevatinib 300 mg QD until disease progression or the subject experienced unacceptable toxicity.

Subjects who discontinued tesevatinib therapy were followed for survival.

Subjects with NSCLC + EGFR mutations were assigned to one of three cohorts:

* Cohort A: Brain Metastases (BM). Subjects had progressed with BM.
* Cohort B: Leptomeningeal Metastases (LM). Subjects had initially presented or progressed with LM.
* Cohort C: Brain Metastases at Initial Presentation (BM-IP). Subjects had no prior systemic therapy.

Each of the three cohorts was to have 20 subjects, for a total of 60 subjects. All three cohorts were enrolled simultaneously.

The primary objectives were to include:

* Clinical activity of tesevatinib of subjects in Cohort A (BM) and Cohort C (BM-IP) as measured by Response Criteria in Solid Tumors (RECIST) version 1.1 which evaluated changes in BM size.
* Clinical activity of tesevatinib of subjects in Cohort B (LM) as measured by improvement in Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 symptoms and signs.

Efficacy assessments included response to treatment using RECIST criteria, progression-free survival (PFS), time to progression (TTP), overall survival (OS), and Quality of Life (QOL) questionnaires. Safety assessments included adverse event (AE) monitoring, electrocardiogram (ECG), Eastern Cooperative Oncology Group (ECOG) Performance Status, laboratory testing, physical examination, vital signs, and pregnancy testing. In addition, pharmacokinetic (PK) and pharmacodynamic (PD) assessments were performed.

An End of Treatment Visit occurred within 3 days after the subject's last dose of study drug. This could have occurred at the visit when disease progression was diagnosed. Subjects were continued to be followed for disease progression and survival.

A follow-up visit occurred 30 days (± 5 days) after the last dose of study drug. This visit may have occurred prior to 30 days if a new therapy was started within 30 days of last dose of study drug.

For long-term follow-up, after subjects withdrew from the active treatment portion of the study, they were contacted by telephone every 8 weeks to assess survival status and any subsequent anti-cancer treatment.

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

A Phase 2, Multicenter Study of Tesevatinib in Subjects With Non-Small Cell Lung Cancer, EGFR Activating Mutation, Prior Treatment With a Tyrosine Kinase Inhibitor, and Brain Metastases or Leptomeningeal Metastases

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.

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.

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

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

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

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

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

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.

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.

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.

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.

Tesevatinib 300 mg administered orally (PO) once daily (QD) to subjects with NSCLC who have progressed with BM

Cohort A - Brain Metastases

Tesevatinib 300 mg administered PO to subjects with NSCLC who have progressed with LM

Cohort B - Leptomeningeal Metastases

Tesevatinib 300 mg administered PO to subjects with NSCLC who presented initially with brain metastases

Cohort C - Brain Metastases at Initial Presentation

Tesevatinib 300 mg administered PO to all subjects with NSCLC who had brain metastases and who had leptomeningeal metastases

All Subjects (Cohorts A+B+C)

Tesevatinib will be orally administered with a dose of 300 mg once daily to subjects with NSCLC who have progressed with BM

Tesevatinib

Tesevatinib will be orally administered with a dose of 300 mg once daily to subjects with NSCLC who have progressed with LM

Tesevatinib

Tesevatinib will be orally administered with a dose of 300 mg once daily to subjects with NSCLC with BM at initial presentation

Tesevatinib

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Cancer 30 (C30) is 30-question assessment scales: 5 functional; 3 symptom; 1 global QoL scale and, 6 single items; rated on 4-point scale (not at all, a little, quite a bit, very much) scored 0 to 100. High score for functional scale = high/healthy functioning; high score for global health = high QoL; but high score for symptom scale = high level of symptomatology/problems.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer	NCT02154529	HER-2 Positive ... Metastatic Mali...	Tesevatinib Trastuzumab	18 Years -	Kadmon Corporation, LLC
Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer	NCT02154529	HER-2 Positive ... Metastatic Mali...	Tesevatinib Trastuzumab	18 Years -	Kadmon Corporation, LLC
Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma	NCT02844439	Glioblastoma Recurrent Gliob... Brain Tumor	Tesevatinib	18 Years -	Kadmon Corporation, LLC
Phase 2 Study of Study of Tesevatinib in Subjects With NSCLC and Brain or Leptomeningeal Metastases	NCT02616393	Non-Small Cell ... Leptomeningeal ... Brain Metastase...	Tesevatinib	18 Years -	Kadmon Corporation, LLC
Study of Tesevatinib Monotherapy in Patients With Recurrent Glioblastoma	NCT02844439	Glioblastoma Recurrent Gliob... Brain Tumor	Tesevatinib	18 Years -	Kadmon Corporation, LLC

Spots Global Cancer Trial Database for tesevatinib

Every month we try and update this database with for tesevatinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tesevatinib

Every month we try and update this database with for tesevatinib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tesevatinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.