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| Name | Class |
|---|---|
| Plexxikon | INDUSTRY |
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PLX3397 is a selective inhibitor of Fms, Kit, and oncogenic Flt3 activity. The primary objective of this study is to evaluate the safety and pharmacokinetics of orally administered PLX3397 in patients with advanced, incurable, solid tumors in which these target kinases are linked to disease pathophysiology. The secondary objective is to measure the pharmacodynamic activity of PLX3397 via blood, plasma and urine biomarkers of Fms activity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PLX3397 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PLX3397 | Drug | Capsules administered once or twice daily, continuous dosing |
|
| Measure | Description | Time Frame |
|---|---|---|
| Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Escalation (Efficacy Evaluable Population) | Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose) |
| Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension (Efficacy Evaluable Population) | Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose) |
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Inclusion Criteria:
Age 18 and older
Solid tumors refractory to standard therapy
For the Extension cohorts, patients must have measurable disease by RECIST criteria and meet the following disease-specific criteria:
Eastern Cooperative Oncology Group performance status 0 or 1
Life expectancy >= 3 months
Adequate hepatic, renal, and bone marrow function
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Daiichi Sankyo | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HonorHealth | Scottsdale | Arizona | 85258 | United States | ||
| UCLA |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34716196 | Derived | Tap WD, Singh AS, Anthony SP, Sterba M, Zhang C, Healey JH, Chmielowski B, Cohn AL, Shapiro GI, Keedy VL, Wainberg ZA, Puzanov I, Cote GM, Wagner AJ, Braiteh F, Sherman E, Hsu HH, Peterfy C, Gelhorn HL, Ye X, Severson P, West BL, Lin PS, Tong-Starksen S. Results from Phase I Extension Study Assessing Pexidartinib Treatment in Six Cohorts with Solid Tumors including TGCT, and Abnormal CSF1 Transcripts in TGCT. Clin Cancer Res. 2022 Jan 15;28(2):298-307. doi: 10.1158/1078-0432.CCR-21-2007. Epub 2021 Oct 29. | |
| 33289960 |
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De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
At least 3 participants and up to 6 participants were to be enrolled in each dose level using 100% dose increments for each level in the absence of Grade 2 or greater drug-attributable toxicity. Dose escalation was only permitted if adequate safety and tolerability were observed at the previous lower dose for 28 days for the first 3 participants.
The dose escalation phase administered ascending daily oral doses of PLX3397 to patients with solid tumors and evaluated PK and toxicity. Once the recommended phase 2 dose was reached, 6 extension cohorts were enrolled, consisting of a variety of tumor types.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Escalation Cohort 1: 200 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. |
| FG001 | Dose Escalation Cohort 2: 300 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. |
| FG002 | Dose Escalation Cohort 3: 400 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. |
| FG003 | Dose Escalation Cohort 4: 600 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. |
| FG004 | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. |
| FG005 | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. |
| FG006 | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. |
| FG007 | Dose Extension: MEC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with advanced or recurrent mucoepidermoid carcinoma (MEC) who received PLX3397. |
| FG008 | Dose Extension: PVNS Cohort PVNS Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. |
| FG009 | Dose Extension: GIST Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with advanced gastrointestinal stromal tumor (GIST) who received PLX3397. |
| FG010 | Dose Extension: ATC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397. |
| FG011 | Dose Extension: Malignant Effusion Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with advanced solid tumors with malignant effusion who received PLX3397. |
| FG012 | Dose Extension: Other Tumors 1000 mg/Day (600mg AM, 400mg PM) | Participants with other solid tumor types who received PLX3397. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Escalation Cohort 1: 200 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. |
| BG001 | Dose Escalation Cohort 2: 300 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Escalation (Efficacy Evaluable Population) | Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Best overall tumor response was assessed in the Efficacy Evaluable Population. | Posted | Count of Participants | Participants | Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose) |
Adverse events (and serious adverse events) were recorded from the time the participant received the first dose of study drug up to 30 days after the last dose, up to approximately 30 months postdose.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Escalation Cohort 1: 200 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 200 mg QD. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA (12.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Daiichi Sankyo Inc. | 908-992-6400 | CTRinfo@dsi.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 25, 2020 | Nov 30, 2021 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| C000600259 | pexidartinib |
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| Duration of Response (Efficacy Evaluable Population) - Dose Extension | Duration of Response (DOR) is defined as the number of days from the date of initial response (CR or PR confirmed at least 28 days later) to the date of first documented disease progression/relapse or death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, DOR is censored as of the date of their last imaging exam of target or non-target lesions prior to post-surgery and/or off-treatment scans. | From initial response until disease progression or death, up to approximately 30 months postdose |
| Progression-free Survival (Efficacy Evaluable Population) - Dose Extension | Progression-Free Survival (PFS) is defined as the number of days from the first day of treatment to the first documented disease progression or date of death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, PFS is censored at the date of last evaluable tumor assessment. | From Cycle 1 Day 1 to disease progression or death |
| Best Overall Tumor Response (PVNS Cohort) Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension | Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Every 2 months beginning Cycle 3, Day 1 until disease progression |
| Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Cmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation | Cycle 1 Day 15 pharmacokinetic (PK) timepoints taken are: For once daily (QD) dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For twice a day (BID) dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned. | Cycle 1, Day 15 |
| Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Tmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation | Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned. | Cycle 1, Day 15 |
| Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Area Under the Curve (AUC0-24), Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation | Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing, predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned. | Cycle 1, Day 15 (QD dosing: predose [morning] and 0.5, 1, 2, 4, and 8 hours postdose; BID dosing: predose [morning] and 1, 2, 4, and 7 hours postdose) |
| Numeric Rating Scale (NRS) for PVNS Symptoms Sum of Scores Through Cycle 2 (Efficacy Evaluable Population) - Dose Extension | The NRS for PVNS Symptoms instrument is a 5-item self-administered questionnaire to assess the "worst" of each of the symptoms pain, swelling, stiffness, instability and limited motion in the last 24 hours. A 0 to 10 NRS is provided for each symptom. For pain, 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine". For the other 4 symptoms, 0 indicates "no (symptom)" and 10 indicates "(symptom) worst imaginable", e.g., "swelling - worst imaginable." Higher scores indicated worse outcome. | Baseline, Cycle 1 Day 15, Cycle 2, Cycle 3, Cycle 12, Cycle 24, Cycle 36, and Cycle 46 (each cycle was 28 days) |
| Los Angeles |
| California |
| 90404 |
| United States |
| Rocky Mountain Cancer Centers | Denver | Colorado | 80218 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| Comprehensive Cancer Centers of Nevada | Las Vegas | Nevada | 89169 | United States |
| Memorial Sloan-Kettering Cancer Center (MSKCC) | New York | New York | 10065 | United States |
| Pennsylvania Oncology Hematology Associates | Philadelphia | Pennsylvania | 19106 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| Vanderbilt-Ingram Medical Center | Nashville | Tennessee | 37232 | United States |
| Texas Oncology, PA (North) | Dallas | Texas | 75246 | United States |
| Virginia Oncology Associates | Norfolk | Virginia | 23502 | United States |
| Evergreen Hematology & Oncology | Spokane | Washington | 99218 | United States |
| Derived |
| Lewis JH, Gelderblom H, van de Sande M, Stacchiotti S, Healey JH, Tap WD, Wagner AJ, Pousa AL, Druta M, Lin CC, Baba HA, Choi Y, Wang Q, Shuster DE, Bauer S. Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors. Oncologist. 2021 May;26(5):e863-e873. doi: 10.1002/onco.13629. Epub 2020 Dec 24. |
| 26222558 | Derived | Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, Chmielowski B, Staddon AP, Cohn AL, Shapiro GI, Keedy VL, Singh AS, Puzanov I, Kwak EL, Wagner AJ, Von Hoff DD, Weiss GJ, Ramanathan RK, Zhang J, Habets G, Zhang Y, Burton EA, Visor G, Sanftner L, Severson P, Nguyen H, Kim MJ, Marimuthu A, Tsang G, Shellooe R, Gee C, West BL, Hirth P, Nolop K, van de Rijn M, Hsu HH, Peterfy C, Lin PS, Tong-Starksen S, Bollag G. Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. N Engl J Med. 2015 Jul 30;373(5):428-37. doi: 10.1056/NEJMoa1411366. |
| Physician Decision |
|
| Adverse Event |
|
| Protocol Violation |
|
| Lost to Follow-up |
|
| Non-compliance |
|
| Other |
|
| Patient decision |
|
| Transitioned to Phase 4 study |
|
| Patient completed 12-week follow-up and continued on commercially approved drug |
|
| Patient withdrew |
|
| Surgical resection |
|
| Patient maintained complete response status throughout drug holiday |
|
| Study termination by Sponsor |
|
| BG002 | Dose Escalation Cohort 3: 400 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. |
| BG003 | Dose Escalation Cohort 4: 600 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. |
| BG004 | Dose Escalation Cohort 5: 900 mg/Day | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. |
| BG005 | Dose Escalation Cohort 6: 1200 mg/Day | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. |
| BG006 | Dose Escalation Cohort 7: 1000 mg/Day | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. |
| BG007 | Dose Extension: MEC Cohort | Participants with advanced mucoepidermoid carcinoma (MEC) who received PLX3397. |
| BG008 | Dose Extension: PVNS Cohort | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. |
| BG009 | Dose Extension: GIST Cohort | Participants with advanced gastrointestinal stromal tumor (GIS) who received PLX3397. |
| BG010 | Dose Extension: ATC Cohort | Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397. |
| BG011 | Dose Extension: Malignant Effusion Cohort | Participants with advanced solid tumors with malignant effusion who received PLX3397. |
| BG012 | Dose Extension: Other Solid Tumor Type Cohort | Participants with other solid tumor types who received PLX3397. |
| BG013 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
| Primary | Summary of Derived Best Tumor Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension (Efficacy Evaluable Population) | Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Best overall tumor response was assessed in the Efficacy Evaluable Population. | Posted | Count of Participants | Participants | No | Every 2 months beginning Cycle 3, Day 1 until disease progression (up to approximately 30 months postdose) |
|
|
|
| Primary | Duration of Response (Efficacy Evaluable Population) - Dose Extension | Duration of Response (DOR) is defined as the number of days from the date of initial response (CR or PR confirmed at least 28 days later) to the date of first documented disease progression/relapse or death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, DOR is censored as of the date of their last imaging exam of target or non-target lesions prior to post-surgery and/or off-treatment scans. | Duration of response was assessed among participants with response of CR or PR in the Efficacy Evaluable Population. | Posted | Median | 95% Confidence Interval | days | From initial response until disease progression or death, up to approximately 30 months postdose |
|
|
|
| Primary | Progression-free Survival (Efficacy Evaluable Population) - Dose Extension | Progression-Free Survival (PFS) is defined as the number of days from the first day of treatment to the first documented disease progression or date of death, whichever occurs first. If no disease progression or death is documented prior to study termination, analysis cutoff, or the start of confounding anticancer therapy, PFS is censored at the date of last evaluable tumor assessment. | Progression-free survival was assessed in the Efficacy Evaluable Population. | Posted | Median | 95% Confidence Interval | days | From Cycle 1 Day 1 to disease progression or death |
|
|
|
| Primary | Best Overall Tumor Response (PVNS Cohort) Per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 - Dose Extension | Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | Best overall tumor response was assessed in the Efficacy Evaluable Population. | Posted | Count of Participants | Participants | Every 2 months beginning Cycle 3, Day 1 until disease progression |
|
|
|
| Primary | Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Cmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation | Cycle 1 Day 15 pharmacokinetic (PK) timepoints taken are: For once daily (QD) dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For twice a day (BID) dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Median | Full Range | ng/mL | Cycle 1, Day 15 |
|
|
|
| Primary | Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Tmax, Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation | Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Median | Full Range | hour | Cycle 1, Day 15 |
|
|
|
| Primary | Summary Statistics for Selected PLX3397 Pharmacokinetics Parameter Area Under the Curve (AUC0-24), Study Day Cycle 1 Day 15, Stratified by Cohort - Dose Escalation | Cycle 1 Day 15 PK timepoints taken are: For QD dosing, obtained predose (morning) and 0.5, 1, 2, 4, and 8 hours postdose. For BID dosing, predose (morning) and 1, 2, 4, and 7 hours postdose. The second dose will then be administered, and PK obtained 1 hour post the second dose (8 hours post the first dose). For BID dosing, no run-in is planned. | Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set. | Posted | Median | Full Range | ng*hr/mL | Cycle 1, Day 15 (QD dosing: predose [morning] and 0.5, 1, 2, 4, and 8 hours postdose; BID dosing: predose [morning] and 1, 2, 4, and 7 hours postdose) |
|
|
|
| Primary | Numeric Rating Scale (NRS) for PVNS Symptoms Sum of Scores Through Cycle 2 (Efficacy Evaluable Population) - Dose Extension | The NRS for PVNS Symptoms instrument is a 5-item self-administered questionnaire to assess the "worst" of each of the symptoms pain, swelling, stiffness, instability and limited motion in the last 24 hours. A 0 to 10 NRS is provided for each symptom. For pain, 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine". For the other 4 symptoms, 0 indicates "no (symptom)" and 10 indicates "(symptom) worst imaginable", e.g., "swelling - worst imaginable." Higher scores indicated worse outcome. | NRS for PVNS symptoms were assessed in patients with available data in the Efficacy Evaluable Population. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Cycle 1 Day 15, Cycle 2, Cycle 3, Cycle 12, Cycle 24, Cycle 36, and Cycle 46 (each cycle was 28 days) |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | Dose Escalation Cohort 2: 300 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 300 mg QD. | 1 | 6 | 1 | 6 | 6 | 6 |
| EG002 | Dose Escalation Cohort 3: 400 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 400 mg QD. | 1 | 6 | 0 | 6 | 6 | 6 |
| EG003 | Dose Escalation Cohort 4: 600 mg QD | Participants with advanced, incurable, solid tumors who received PLX3397 600 mg QD. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG004 | Dose Escalation Cohort 5: 900 mg/Day (500mg AM, 400mg PM) | Participants with advanced, incurable, solid tumors who received PLX3397 900 mg/day. | 0 | 7 | 1 | 7 | 6 | 7 |
| EG005 | Dose Escalation Cohort 6: 1200 mg/Day (600mg BID) | Participants with advanced, incurable, solid tumors who received PLX3397 1200 mg/day. | 1 | 6 | 1 | 6 | 6 | 6 |
| EG006 | Dose Escalation Cohort 7: 1000 mg/Day (500mg BID) | Participants with advanced, incurable, solid tumors who received PLX3397 1000 mg/day. | 0 | 7 | 3 | 7 | 7 | 7 |
| EG007 | MEC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with advanced or recurrent mucoepidermoid carcinoma (MEC) who received PLX3397. | 1 | 4 | 2 | 4 | 4 | 4 |
| EG008 | PVNS Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with advanced pigmented villonodular synovitis (PVNS) who received PLX3397. | 0 | 39 | 5 | 39 | 39 | 39 |
| EG009 | GIST Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with advanced gastrointestinal stromal tumor (GIST) who received PLX3397. | 3 | 11 | 4 | 11 | 11 | 11 |
| EG010 | ATC Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with anaplastic thyroid carcinoma (ATC) who received PLX3397. | 1 | 9 | 1 | 9 | 8 | 9 |
| EG011 | Malignant Effusion Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with advanced solid tumors with malignant effusion who received PLX3397. | 1 | 8 | 2 | 8 | 8 | 8 |
| EG012 | Other Solid Tumor Type Cohort 1000 mg/Day (600mg AM, 400mg PM) | Participants with other solid tumor types who received PLX3397. | 1 | 20 | 3 | 20 | 20 | 20 |
| Bacterial sepsis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hepatic haemorrhage | Hepatobiliary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.1) | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Hair colour changes | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Periorbital oedema | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Skin hypopigmentation | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Swelling face | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Retching | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Faecal incontinence | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oesophageal stenosis | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Infusion site pain | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Increased tendency to bruise | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypogeusia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Parosmia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Sedation | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Bronchial obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Paranasal sinus hypersecretion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Bunion | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Blood thyroid stimulating hormone increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Neutrophil count increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Occult blood positive | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Prothrombin time prolonged | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Bronchitis viral | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Oesophageal candidiasis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Disorientation | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Distractibility | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Impulsive behaviour | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Seroma | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Eye discharge | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Orbital oedema | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Breast mass | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
|
| Genital haemorrhage | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA (12.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (12.1) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lacrimation increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Amnesia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Fluid retention | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hair growth abnormal | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.1) | Systematic Assessment |
|
| Pallor | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Skin depigmentation | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Abnormal dreams | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Blood blister | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Diplopia | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Early satiety | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Myodesopsia | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (12.1) | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Anaphylactic transfusion reaction | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
|
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Bacterial sepsis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Blood creatinine phosphokinase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Blood glucose decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Ear discomfort | Ear and labyrinth disorders | MedDRA (12.1) | Systematic Assessment |
|
| Electromechanical dissociation | Cardiac disorders | MedDRA (12.1) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Fibromyalgia | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hepatic haemorrhage | Hepatobiliary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
|
| Mental impairment | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Nasal septum ulceration | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Oedema | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (12.1) | Systematic Assessment |
|
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Palmar erythema | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Peritonitis bacterial | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Rosacea | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA (12.1) | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
| Sleep talking | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
|
| Small intestine obstruction | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Superior vena caval occlusion | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
| Tooth discolouration | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Troponin increased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.1) | Systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
|
| Bundle branch block right | Cardiac disorders | MedDRA (12.1) | Systematic Assessment |
|
| Exophthalmos | Eye disorders | MedDRA (12.1) | Systematic Assessment |
|
| Diverticulum | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hepatic steatosis | Hepatobiliary disorders | MedDRA (12.1) | Systematic Assessment |
|
| Fungal skin infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
|
| Menstruation irregular | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
|
| Hair texture abnormal | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
|
Not provided
Not provided
| PR |
|
| SD |
|
| PD |
|
| NE |
|
| Overall response rate (CR or PR) |
|
| Title | Measurements |
|---|
|
| PD |
|
| NE |
|
| Overall response rate (CR or PR) |
|
|
| Pain; Cycle 2 |
|
|
| Pain; Cycle 3 |
|
|
| Pain; Cycle 12 |
|
|
| Pain; Cycle 24 |
|
|
| Pain; Cycle 36 |
|
|
| Pain; Cycle 46 |
|
|
| Swelling; Baseline |
|
|
| Swelling; Cycle 1 Day 15 |
|
|
| Swelling; Cycle 2 |
|
|
| Swelling; Cycle 3 |
|
|
| Swelling; Cycle 12 |
|
|
| Swelling; Cycle 24 |
|
|
| Swelling; Cycle 36 |
|
|
| Swelling; Cycle 46 |
|
|
| Stiffness; Baseline |
|
|
| Stiffness; Cycle 1 Day 15 |
|
|
| Stiffness; Cycle 2 |
|
|
| Stiffness; Cycle 3 |
|
|
| Stiffness; Cycle 12 |
|
|
| Stiffness; Cycle 24 |
|
|
| Stiffness; Cycle 36 |
|
|
| Stiffness; Cycle 46 |
|
|
| Instability; Baseline |
|
|
| Instability; Cycle 1 Day 15 |
|
|
| Instability; Cycle 2 |
|
|
| Instability; Cycle 3 |
|
|
| Instability; Cycle 12 |
|
|
| Instability; Cycle 24 |
|
|
| Instability; Cycle 36 |
|
|
| Instability; Cycle 46 |
|
|
| Limited motion; Baseline |
|
|
| Limited motion; Cycle 1 Day 15 |
|
|
| Limited motion; Cycle 2 |
|
|
| Limited motion; Cycle 3 |
|
|
| Limited motion; Cycle 12 |
|
|
| Limited motion; Cycle 24 |
|
|
| Limited motion; Cycle 36 |
|
|
| Limited Motion; Cycle 46 |
|
|