Brain Tumor, Glioblastoma, Recurrent Glioblastoma
Conditions
Brief summary
This is a multicenter, Phase 2 study to assess the activity of tesevatinib in patients with recurrent glioblastoma.
Detailed description
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.
Interventions
DRUGTesevatinib
Sponsors
Kadmon Corporation, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator 2. Age ≥ 18 years old 3. Kamofsky performance status ≥70% 4. Stable or decreasing dose of corticosteroids within 5 days prior to study 5. enrollment. 5. For women who are not postmenopausal (i.e., \< 12 months after last menstruation) or surgically sterile (absence of ovaries and/or uterus) and who are sexually active: agreement to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the treatment period and for at least 6 months after the last dose of study drug. 6. For male patients who are sexually active and who are partners of premenopausal women: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug. 7. Histologically confirmed glioblastoma. A local pathology report constitutes adequate documentation of histology for study inclusion. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma. 8. First recurrence after concurrent or adjuvant chemoradiotherapy. Imaging confirmation of first tumor progression or regrowth as defined by the RANO criteria . A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling. 9. Prior treatment with TMZ for low grade glioma or glioblastoma. 10. No more than one prior line of systemic treatment for glioblastoma. Concurrent and adjuvant TMZ-based chemotherapy, including the combination of TMZ with an investigational agent, is considered one line of therapy. 11. Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field. 12. Recovery from the toxic effects of prior therapy, with a minimum time of: 1. ≥ 28 days elapsed from the administration of any prior cytotoxic agents, except ≥ 14 days from vincristine, ≥ 21 days from procarbazine, and ≥ 42 days from nitrosureas 2. ≥ 28 days elapsed from the administration of any investigational agent 3. ≥ 14 days elapsed from administration of any non-cytotoxic agent (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid) 13. Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that: 1. Surgery must have confirmed the recurrence 2. There must be residual disease 3. A minimum of 28 days must have elapsed from the day of surgery to first dose of the study drug. For core or needle biopsy, a minimum of 7 days must have elapsed prior to study entry 14. Availability of formalin-fixed paraffin-embedded tumor tissue diagnostic of glioblastoma.
Exclusion criteria
1. Concurrent therapeutic intervention (including radiation therapy and NovoTTF). 2. Prior exposure to EGFR inhibitors. 3. Prior exposure to bevacizumab or other VEGF- or VEGF-receptor-targeted agent within 8 weeks of study start. 4. Prior treatment with prolifeprospan 20 with carmustine wafer. 5. Prior intracerebral agent. 6. Evidence of recent hemorrhage on baseline MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, or presence of punctuate hemorrhage in the tumor are eligible. 7. Need for urgent palliative intervention for primary disease (e.g., rapidly increasing intracranial pressure, impending herniation, uncontrolled seizures). 8. Hematology: ANC \< 1.5 x109/L; Plt \< 100 x109/L Hgb \< 9.0 g/dL within 7 days prior to enrollment. The use of transfusion or other intervention to achieve Hb ≥ 9 g/dL is acceptable. 9. T.Bili. ≥ 1.5 x ULN (except in patients diagnosed with Gilbert's disease). 10. AST(SGOT), ALT(SGPT), or alkaline phosphatase (ALP) ≥ 2.5 x ULN. 11. S. Creat. \> 1.5 x ULN. 12. K+ or Mg+ \< LLN. 13. In the absence of therapeutic intent to anticoagulate the patient: INR \> 1.5 or PT \> 1.5 xULN or aPTT \> 1.5 xULN Therapeutic anticoagulation. 14. Known contraindication to MRI, such as cardiac pacemaker, shrapnel or ocular foreign body. 15. Used any prescription medication during the prior 2 weeks that the investigator judges is likely to interfere with the study or to pose an additional risk to the patient in participating, specifically inhibitors or inducers of cytochrome P450 (CYP)3A4 (refer to Appendix 5). A stable regimen (≥ 4 weeks) of antidepressants of the selective serotonin re-uptake inhibitor (SSRI) class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline, and fluoxetine). 16. Taking any drugs associated with torsades de pointes or known to moderately or severely prolong the QTc(F) interval 17. History of torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (\< 50 bpm), heart block (excluding first degree block, being PR interval only), or congenital long QT syndrome. Patients with a history of atrial arrhythmias should be discussed with the Medical Monitor. 18. Uncontrolled diabetes, as evidenced by fasting serum glucose level \>200 mg/dL 19. New York Heart Association (NYHA) Grade II or greater congestive cardiac failure. 20. Has marked prolongation of QTc(F) interval at screening or baseline (QTc\[F\] interval \> 470 msec) using the Fridericia method of correction for heart rate. 21. History of myocardial infarction (within 12 months) or unstable angina (within 6 months) prior to study enrolment. 22. History of stroke or transient ischemic attacks within 6 months prior to study enrolment. 23. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study enrolment. 24. Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation). 25. History of intracranial abscess within 6 months prior to study enrolment. 26. History of another malignancy in the previous 3 years, with a disease-free interval of \< 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. 27. Evidence of any active infection requiring hospitalization or IV antibiotics within 2 weeks prior to study enrolment. 28. Known hypersensitivity to any excipients of tesevatinib. 29. Inability to swallow or absorb orally-administered medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Median Progression-free Survival (PFS) Rate at 6 Months (PFS-6) | 6 months | Proportion (%) of subjects who did not have progressive disease after treatment with tesevatinib at 6 months (PFS-6) after baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Median PFS | Until disease progression, unacceptable toxicity, subject or clinician decision to discontinue, death, or up to 3 years, whichever occurred first | Median duration (months) of subjects who were progression-free of disease from baseline |
| Efficacy: Median OS | Until unacceptable toxicity, subject or investigator decision to discontinue, death, or up to 3 years, whichever occurred first | Median duration (months) subjects survived from baseline until death |
| Efficacy: Best Overall Response | Until disease progression, unacceptable toxicity, subject or investigator decision to discontinue, death, or up to 3 years, whichever occurred first | 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) |
| Efficacy: Objective Response Rate (ORR) | Until disease progression, unacceptable toxicity, subject or investigator decision to discontinue, death, or 3 years, whichever occurred first | Proportion (%) of subjects who had either a complete response (CR) or a partial response (PR) to treatment with tesevatinib |
| Efficacy: Median Overall Survival Rate at 9 Months (OS-9) | 9 months | Median proportion (%) of subjects who survived 9 months after baseline |
| Exposure to Tesevatinib: Overall Median | Until disease progression, unacceptable toxicity, subject or investigator decision, death, or up to 3 years, whichever occurred first | Median amount of tesevatinib (mg) subjects received during the study |
| Exposure to Tesevatinib: Mean Number of Cycles | Until disease progression, unacceptable toxicity, subject or investigator decision, death, or up to 3 years, whichever occurred first. | Mean number of 28-day cycles of treatment with tesevatinib subjects received during the study |
| Exposure to Tesevatinib: Median Number of Cycles | Until disease progression, unacceptable toxicity, subject or investigator decision, death, or up to 3 years, whichever occurred first | Median number of 28-day cycles of treatment with tesevatinib subjects received during the study |
| Exposure to Tesevatinib: Overall Mean | Until disease progression, unacceptable toxicity, subject or investigator decision, death, or up to 3 years, whichever occurred first | Mean total amount of tesevatinib (mg) subjects received during the study |
Countries
United States
Participant flow
Recruitment details
Subjects at least 18 years of age with recurrent glioblastoma and no concurrent therapeutic intervention including prior exposure to EGFR inhibitors, VEGF, carmustine wafer, or intracerebral agent
Pre-assignment details
A total of 40 subjects with recurrent glioblastoma were enrolled. Tumor samples were evaluated for the presence or absence of EGFR gene-amplification, designated Sub-population A, and/or the EGFR variant III mutation (EGFRvIII\^pos), designated Sub-population B, or neither EGFR gene-amplification nor EGFRvIII\^pos variant mutation. Note: EGFR = epidermal growth factor receptor; EGFR vIII\^pos = EGFR variant 3 mutation; VEGF = vascular endothelial growth factor
Participants by arm
| Arm | Count |
|---|---|
| Total: All Subjects Subjects with recurrent glioblastoma who had or did not have EGFR gene-amplified glioblastoma and/or EGFRvIII\^pos variant | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 28 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 5 |
| Overall Study | Termination by Sponsor | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Total: All Subjects |
|---|---|
| Age, Continuous All Subjects | 55.9 Years STANDARD_DEVIATION 9.88 |
| Age, Continuous Sub-population A | 55.9 Years STANDARD_DEVIATION 8.37 |
| Age, Continuous Sub-population B | 56.8 Years STANDARD_DEVIATION 8.49 |
| Age, Customized All Subjects | 58.0 Years |
| Age, Customized Sub-population A | 57.5 Years |
| Age, Customized Sub-population B | 58.0 Years |
| Best Overall Response All Subjects CR | 0 Participants |
| Best Overall Response All Subjects PD | 9 Participants |
| Best Overall Response All Subjects PR | 0 Participants |
| Best Overall Response All Subjects SD | 21 Participants |
| Best Overall Response All Subjects Unknown | 10 Participants |
| Best Overall Response Sub-population A CR | 0 Participants |
| Best Overall Response Sub-population A PD | 6 Participants |
| Best Overall Response Sub-population A PR | 0 Participants |
| Best Overall Response Sub-population A SD | 12 Participants |
| Best Overall Response Sub-population A Unknown | 6 Participants |
| Best Overall Response Sub-population B CR | 0 Participants |
| Best Overall Response Sub-population B PD | 1 Participants |
| Best Overall Response Sub-population B PR | 0 Participants |
| Best Overall Response Sub-population B SD | 5 Participants |
| Best Overall Response Sub-population B Unknown | 5 Participants |
| Corticosteroid Used at Baseline All Subjects Dose decreased | 0 Participants |
| Corticosteroid Used at Baseline All Subjects Dose increased | 0 Participants |
| Corticosteroid Used at Baseline All Subjects Dose stable | 1 Participants |
| Corticosteroid Used at Baseline All Subjects None | 3 Participants |
| Corticosteroid Used at Baseline All Subjects Unknown | 36 Participants |
| Corticosteroid Used at Baseline Sub-population A Dose decreased | 0 Participants |
| Corticosteroid Used at Baseline Sub-population A Dose increased | 0 Participants |
| Corticosteroid Used at Baseline Sub-population A Dose stable | 1 Participants |
| Corticosteroid Used at Baseline Sub-population A None | 2 Participants |
| Corticosteroid Used at Baseline Sub-population A Unknown | 21 Participants |
| Corticosteroid Used at Baseline Sub-population B Dose decreased | 0 Participants |
| Corticosteroid Used at Baseline Sub-population B Dose increased | 0 Participants |
| Corticosteroid Used at Baseline Sub-population B Dose stable | 1 Participants |
| Corticosteroid Used at Baseline Sub-population B None | 0 Participants |
| Corticosteroid Used at Baseline Sub-population B Unknown | 10 Participants |
| Ethnicity (NIH/OMB) All Subjects Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) All Subjects Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) All Subjects Unknown or Not Reported | 1 Participants |
| Ethnicity (NIH/OMB) Sub-population A (EGFRvIII^pos glioblastoma) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Sub-population A (EGFRvIII^pos glioblastoma) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Sub-population A (EGFRvIII^pos glioblastoma) Unknown or Not Reported | 1 Participants |
| Ethnicity (NIH/OMB) Sub-population B Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Sub-population B Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Sub-population B Unknown or Not Reported | 0 Participants |
| Karnofsky Performance Status (KPS) All Subjects 100 (Score) | 0 Participants |
| Karnofsky Performance Status (KPS) All Subjects 50 (Score) | 0 Participants |
| Karnofsky Performance Status (KPS) All Subjects 60 (Score) | 0 Participants |
| Karnofsky Performance Status (KPS) All Subjects 70 (Score) | 6 Participants |
| Karnofsky Performance Status (KPS) All Subjects 80 (Score) | 15 Participants |
| Karnofsky Performance Status (KPS) All Subjects 90 (Score) | 19 Participants |
| Karnofsky Performance Status (KPS) Sub-population 100 (Score) | 0 Participants |
| Karnofsky Performance Status (KPS) Sub-population 50 (Score) | 0 Participants |
| Karnofsky Performance Status (KPS) Sub-population 60 (Score) | 0 Participants |
| Karnofsky Performance Status (KPS) Sub-population 70 (Score) | 1 Participants |
| Karnofsky Performance Status (KPS) Sub-population 80 (Score) | 4 Participants |
| Karnofsky Performance Status (KPS) Sub-population 90 (Score) | 6 Participants |
| Karnofsky Performance Status (KPS) Sub-population A (EGFRvIII^pos glioblastoma) 100 (Score) | 0 Participants |
| Karnofsky Performance Status (KPS) Sub-population A (EGFRvIII^pos glioblastoma) 50 (Score) | 0 Participants |
| Karnofsky Performance Status (KPS) Sub-population A (EGFRvIII^pos glioblastoma) 60 (Score) | 0 Participants |
| Karnofsky Performance Status (KPS) Sub-population A (EGFRvIII^pos glioblastoma) 70 (Score) | 3 Participants |
| Karnofsky Performance Status (KPS) Sub-population A (EGFRvIII^pos glioblastoma) 80 (Score) | 10 Participants |
| Karnofsky Performance Status (KPS) Sub-population A (EGFRvIII^pos glioblastoma) 90 (Score) | 11 Participants |
| Months Since First Diagnosis of Glioblastoma: Mean All Subjects | 12.59 Months STANDARD_DEVIATION 8.658 |
| Months Since First Diagnosis of Glioblastoma: Mean Sub-population A | 13.50 Months STANDARD_DEVIATION 10.032 |
| Months Since First Diagnosis of Glioblastoma: Mean Sub-population B | 13.15 Months STANDARD_DEVIATION 9.01 |
| Months Since First Diagnosis of Glioblastoma: Median All Subjects | 9.95 Months |
| Months Since First Diagnosis of Glioblastoma: Median Sub-population A | 8.50 Months |
| Months Since First Diagnosis of Glioblastoma: Median Sub-population B | 8.50 Months |
| Months Since Recurrent Diagnosis of Glioblastoma: Mean All Subjects | 1.34 Months STANDARD_DEVIATION 2.123 |
| Months Since Recurrent Diagnosis of Glioblastoma: Mean Sub-population A | 1.58 Months STANDARD_DEVIATION 2.707 |
| Months Since Recurrent Diagnosis of Glioblastoma: Mean Sub-population B | 1.14 Months STANDARD_DEVIATION 0.916 |
| Months Since Recurrent Diagnosis of Glioblastoma: Median All Subjects | 0.90 Months |
| Months Since Recurrent Diagnosis of Glioblastoma: Median Sub-population A (EGFRvIII^pos glioblastoma) | 0.80 Months |
| Months Since Recurrent Diagnosis of Glioblastoma: Median Sub-population B | 0.80 Months |
| Number of Prior Systemic Therapy Regimens All Subjects 1 Regimen | 21 Participants |
| Number of Prior Systemic Therapy Regimens All Subjects > 2 Regimens | 2 Participants |
| Number of Prior Systemic Therapy Regimens All Subjects 2 Regimens | 16 Participants |
| Number of Prior Systemic Therapy Regimens All Subjects No Prior Systemic Therapy | 1 Participants |
| Number of Prior Systemic Therapy Regimens Sub-population A 1 Regimen | 13 Participants |
| Number of Prior Systemic Therapy Regimens Sub-population A > 2 Regimens | 0 Participants |
| Number of Prior Systemic Therapy Regimens Sub-population A 2 Regimens | 11 Participants |
| Number of Prior Systemic Therapy Regimens Sub-population A No Prior Systemic Therapy | 0 Participants |
| Number of Prior Systemic Therapy Regimens Sub-population B 1 Regimen | 5 Participants |
| Number of Prior Systemic Therapy Regimens Sub-population B > 2 Regimens | 0 Participants |
| Number of Prior Systemic Therapy Regimens Sub-population B 2 Regimens | 6 Participants |
| Number of Prior Systemic Therapy Regimens Sub-population B No Prior Systemic Therapy | 0 Participants |
| Prior Low Grade Astrocytoma Diagnosis All Subjects No | 38 Participants |
| Prior Low Grade Astrocytoma Diagnosis All Subjects Yes | 2 Participants |
| Prior Low Grade Astrocytoma Diagnosis Sub-population A No | 24 Participants |
| Prior Low Grade Astrocytoma Diagnosis Sub-population A Yes | 0 Participants |
| Prior Low Grade Astrocytoma Diagnosis Sub-population B No | 11 Participants |
| Prior Low Grade Astrocytoma Diagnosis Sub-population B Yes | 0 Participants |
| Prior Radiotherapy--Site Irradiated All Subjects Brain | 29 Participants |
| Prior Radiotherapy--Site Irradiated All Subjects Other | 11 Participants |
| Prior Radiotherapy--Site Irradiated Sub-population Brain | 7 Participants |
| Prior Radiotherapy--Site Irradiated Sub-population Other | 4 Participants |
| Prior Radiotherapy--Site Irradiated Sub-population A Brain | 17 Participants |
| Prior Radiotherapy--Site Irradiated Sub-population A Other | 7 Participants |
| Prior Surgery All Subjects No | 0 Participants |
| Prior Surgery All Subjects Unknown | 1 Participants |
| Prior Surgery All Subjects Yes | 39 Participants |
| Prior Surgery Sub-population A No | 0 Participants |
| Prior Surgery Sub-population A Unknown | 0 Participants |
| Prior Surgery Sub-population A Yes | 24 Participants |
| Prior Surgery Sub-population B No | 0 Participants |
| Prior Surgery Sub-population B Unknown | 0 Participants |
| Prior Surgery Sub-population B Yes | 11 Participants |
| Race (NIH/OMB) All Subjects American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) All Subjects Asian | 4 Participants |
| Race (NIH/OMB) All Subjects Black or African American | 1 Participants |
| Race (NIH/OMB) All Subjects More than one race | 0 Participants |
| Race (NIH/OMB) All Subjects Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) All Subjects Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) All Subjects White | 34 Participants |
| Race (NIH/OMB) Sub-population A American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Sub-population A Asian | 3 Participants |
| Race (NIH/OMB) Sub-population A Black or African American | 0 Participants |
| Race (NIH/OMB) Sub-population A More than one race | 0 Participants |
| Race (NIH/OMB) Sub-population A Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Sub-population A Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Sub-population A White | 21 Participants |
| Race (NIH/OMB) Sub-population B American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Sub-population B Asian | 2 Participants |
| Race (NIH/OMB) Sub-population B Black or African American | 0 Participants |
| Race (NIH/OMB) Sub-population B More than one race | 0 Participants |
| Race (NIH/OMB) Sub-population B Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Sub-population B Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Sub-population B White | 9 Participants |
| Reason Therapy Ended All Subjects Other | 3 Participants |
| Reason Therapy Ended All Subjects Progressive Disease | 24 Participants |
| Reason Therapy Ended All Subjects Study Drug Toxicity | 1 Participants |
| Reason Therapy Ended All Subjects Treatment Completed | 11 Participants |
| Reason Therapy Ended Sub-population A Other | 2 Participants |
| Reason Therapy Ended Sub-population A Progressive Disease | 13 Participants |
| Reason Therapy Ended Sub-population A Study Drug Toxicity | 1 Participants |
| Reason Therapy Ended Sub-population A Treatment Completed | 8 Participants |
| Reason Therapy Ended Sub-population B Other | 1 Participants |
| Reason Therapy Ended Sub-population B Progressive Disease | 4 Participants |
| Reason Therapy Ended Sub-population B Study Drug Toxicity | 1 Participants |
| Reason Therapy Ended Sub-population B Treatment Completed | 5 Participants |
| Sex: Female, Male All Subjects Female | 12 Participants |
| Sex: Female, Male All Subjects Male | 28 Participants |
| Sex: Female, Male Sub-population A Female | 6 Participants |
| Sex: Female, Male Sub-population A Male | 18 Participants |
| Sex: Female, Male Sub-population B Female | 3 Participants |
| Sex: Female, Male Sub-population B Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 28 / 40 | 19 / 24 | 9 / 11 |
| other Total, other adverse events | 40 / 40 | 24 / 24 | 11 / 11 |
| serious Total, serious adverse events | 12 / 40 | 7 / 24 | 2 / 11 |
Outcome results
Primary
Efficacy: Median Progression-free Survival (PFS) Rate at 6 Months (PFS-6)
Proportion (%) of subjects who did not have progressive disease after treatment with tesevatinib at 6 months (PFS-6) after baseline
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total | Efficacy: Median Progression-free Survival (PFS) Rate at 6 Months (PFS-6) | 22.5 Percentage (%) of subjects |
| Sub-population A | Efficacy: Median Progression-free Survival (PFS) Rate at 6 Months (PFS-6) | 25.0 Percentage (%) of subjects |
| Sub-population B | Efficacy: Median Progression-free Survival (PFS) Rate at 6 Months (PFS-6) | 18.2 Percentage (%) of subjects |
Secondary
Efficacy: Best Overall Response
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)
Time frame: Until disease progression, unacceptable toxicity, subject or investigator decision to discontinue, death, or up to 3 years, whichever occurred first
Population: Note: NA = data not available; NE = not evaluable
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Total | Efficacy: Best Overall Response | CR | 0 Participants |
| Total | Efficacy: Best Overall Response | PR | 1 Participants |
| Total | Efficacy: Best Overall Response | SD | 22 Participants |
| Total | Efficacy: Best Overall Response | PD | 13 Participants |
| Total | Efficacy: Best Overall Response | NE | 1 Participants |
| Total | Efficacy: Best Overall Response | NA | 3 Participants |
| Sub-population A | Efficacy: Best Overall Response | NA | 2 Participants |
| Sub-population A | Efficacy: Best Overall Response | CR | 0 Participants |
| Sub-population A | Efficacy: Best Overall Response | PD | 10 Participants |
| Sub-population A | Efficacy: Best Overall Response | NE | 1 Participants |
| Sub-population A | Efficacy: Best Overall Response | PR | 1 Participants |
| Sub-population A | Efficacy: Best Overall Response | SD | 10 Participants |
| Sub-population B | Efficacy: Best Overall Response | PR | 1 Participants |
| Sub-population B | Efficacy: Best Overall Response | SD | 2 Participants |
| Sub-population B | Efficacy: Best Overall Response | NA | 1 Participants |
| Sub-population B | Efficacy: Best Overall Response | PD | 6 Participants |
| Sub-population B | Efficacy: Best Overall Response | CR | 0 Participants |
| Sub-population B | Efficacy: Best Overall Response | NE | 1 Participants |
Secondary
Efficacy: Median OS
Median duration (months) subjects survived from baseline until death
Time frame: Until unacceptable toxicity, subject or investigator decision to discontinue, death, or up to 3 years, whichever occurred first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Total | Efficacy: Median OS | 8.4 Months |
| Sub-population A | Efficacy: Median OS | 7.8 Months |
| Sub-population B | Efficacy: Median OS | 7.6 Months |
Secondary
Efficacy: Median Overall Survival Rate at 9 Months (OS-9)
Median proportion (%) of subjects who survived 9 months after baseline
Time frame: 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total | Efficacy: Median Overall Survival Rate at 9 Months (OS-9) | 42.5 Percentage (%) of subjects |
| Sub-population A | Efficacy: Median Overall Survival Rate at 9 Months (OS-9) | 37.5 Percentage (%) of subjects |
| Sub-population B | Efficacy: Median Overall Survival Rate at 9 Months (OS-9) | 27.3 Percentage (%) of subjects |
Secondary
Efficacy: Median PFS
Median duration (months) of subjects who were progression-free of disease from baseline
Time frame: Until disease progression, unacceptable toxicity, subject or clinician decision to discontinue, death, or up to 3 years, whichever occurred first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Total | Efficacy: Median PFS | 2.3 Months |
| Sub-population A | Efficacy: Median PFS | 1.7 Months |
| Sub-population B | Efficacy: Median PFS | 1.0 Months |
Secondary
Efficacy: Objective Response Rate (ORR)
Proportion (%) of subjects who had either a complete response (CR) or a partial response (PR) to treatment with tesevatinib
Time frame: Until disease progression, unacceptable toxicity, subject or investigator decision to discontinue, death, or 3 years, whichever occurred first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total | Efficacy: Objective Response Rate (ORR) | 2.5 Percentage (%) of participants |
| Sub-population A | Efficacy: Objective Response Rate (ORR) | 4.2 Percentage (%) of participants |
| Sub-population B | Efficacy: Objective Response Rate (ORR) | 9.1 Percentage (%) of participants |
Secondary
Exposure to Tesevatinib: Mean Number of Cycles
Mean number of 28-day cycles of treatment with tesevatinib subjects received during the study
Time frame: Until disease progression, unacceptable toxicity, subject or investigator decision, death, or up to 3 years, whichever occurred first.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Total | Exposure to Tesevatinib: Mean Number of Cycles | 3.8 Number of cycles | Standard Deviation 6.72 |
| Sub-population A | Exposure to Tesevatinib: Mean Number of Cycles | 3.3 Number of cycles | Standard Deviation 6.26 |
| Sub-population B | Exposure to Tesevatinib: Mean Number of Cycles | 1.8 Number of cycles | Standard Deviation 1.54 |
Secondary
Exposure to Tesevatinib: Median Number of Cycles
Median number of 28-day cycles of treatment with tesevatinib subjects received during the study
Time frame: Until disease progression, unacceptable toxicity, subject or investigator decision, death, or up to 3 years, whichever occurred first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Total | Exposure to Tesevatinib: Median Number of Cycles | 2.0 Number of cycles |
| Sub-population A | Exposure to Tesevatinib: Median Number of Cycles | 1.5 Number of cycles |
| Sub-population B | Exposure to Tesevatinib: Median Number of Cycles | 1.0 Number of cycles |
Secondary
Exposure to Tesevatinib: Overall Mean
Mean total amount of tesevatinib (mg) subjects received during the study
Time frame: Until disease progression, unacceptable toxicity, subject or investigator decision, death, or up to 3 years, whichever occurred first
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Total | Exposure to Tesevatinib: Overall Mean | 26670.0 mg (tesevatinib) | Standard Deviation 44533.38 |
| Sub-population A | Exposure to Tesevatinib: Overall Mean | 21752.1 mg (tesevatinib) | Standard Deviation 34748.96 |
| Sub-population B | Exposure to Tesevatinib: Overall Mean | 11481.8 mg (tesevatinib) | Standard Deviation 7024.22 |
Secondary
Exposure to Tesevatinib: Overall Median
Median amount of tesevatinib (mg) subjects received during the study
Time frame: Until disease progression, unacceptable toxicity, subject or investigator decision, death, or up to 3 years, whichever occurred first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Total | Exposure to Tesevatinib: Overall Median | 11850.0 mg (tesevatinib) |
| Sub-population A | Exposure to Tesevatinib: Overall Median | 10350.0 mg (tesevatinib) |
| Sub-population B | Exposure to Tesevatinib: Overall Median | 8700.0 mg (tesevatinib) |