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sponsor decision
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This study will evaluate the safety, tolerability, and efficacy of oral KPT-9274 for the treatment of patients with advanced solid malignancies or non-Hodgkin's lymphoma (NHL).
This is a first-in-human, multi-center, open-label clinical study with separate Dose Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of KPT-9274, a dual inhibitor of PAK4 and NAMPT, in patients with advanced solid malignancies (including sarcoma, colon, lung, melanoma, etc.) or NHL for which all standard therapeutic options considered useful by the investigator have been exhausted.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: KPT-9274 10mg | Experimental | Participants received a 10 milligrams (mg) of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
|
| Part A: KPT-9274 20mg | Experimental | Participants received a 20mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
|
| Part A: KPT-9274 30mg | Experimental | Participants received a 30mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
|
| Part A: KPT-9274 40mg | Experimental | Participants received a 40mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
|
| Part A: KPT-9274 40mg BIW | Experimental | Participants received KPT-9274 40mg of oral tablet biweekly (BIW) during each 28-day cycle. |
|
| Part B: KPT-9274 30mg + Niacin 500mg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KPT-9274 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) for KPT-9274 | The MTD was defined as the highest dose at which less than or equal to (<=) 1 participant experienced a dose limiting toxicity (DLT) in Cycle 1. A DLT was defined as an adverse event (AE) or abnormal laboratory value occurring within the first 28 days of treatment of KPT-9274, excluding those clearly caused by underlying disease, disease progression, or external factors. | From start of study drug administration up to 44 weeks |
| Number of Dose Limiting Toxicities (DLT) Experienced by Participants | A DLT was defined as an AE or abnormal laboratory value occurring within the first 28 days of KPT-9274 treatment, excluding those clearly caused by underlying disease, disease progression, or extraneous causes, and meets any of the criteria for defining dose limiting toxicities. | At Cycle 1 only (28-day cycle) |
| Number of Participants With Adverse Event (AE) of Severity Grade >= 3 or 4, Serious AEs, and AEs Leading to Treatment Discontinuation | The AE severity was graded on a scale from 1 to 4 using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03; any events not specifically listed in the scale were defined as: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening. An SAE was any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. The AE leading to treatment discontinuation in the study. | From start of study drug administration up to 49 weeks |
| Percentage of Participants With Overall Response Rate (ORR) | The ORR was defined as percentage of participants who had a response of partial response (PR) or complete response (CR). The PR was achieved when a participant had at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The CR was achieved in a participant when all target lesions disappeared. Any pathological lymph nodes (whether target or non target) must have reduction in the short axis to <10 millimeter (mm). |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) in Participants Who Received KPT-9274 | Cmax achieved by the KPT-9274 after the first dose administrations. | Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
| Time-to-peak Plasma Concentration (Tmax) in Participants Who Received KPT-9274 |
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Inclusion Criteria:
Participants must meet all of the following inclusion criteria to be eligible to enroll in the Part C of this study.
Should have unresectable advanced, recurrent or metastatic melanoma and must have objective and measurable melanoma by RECIST 1.1 after disease progression on a prior anti-PD-1 or anti-PD-L1 therapy.
ECOG performance status of ≤ 2.
Life expectancy of ≥ 3 months.
Adequate hepatic function:
Adequate renal function:
Adequate hematopoietic function:
Exclusion Criteria:
Participants meeting any of the following exclusion criteria are not eligible to enroll in this study.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Health | Los Angeles | California | 90024 | United States | ||
| University of Colorado Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41824279 | Derived | Razak A, Mahipal A, Diamond JR, Ribas A, Berlin JD, Azmi AS, Mark T, Walker CJ, Chai Y, Kashyap T, Gudi G, Naing A. First-in-Human Phase I Study of KPT-9274, a First-in-Class Dual Inhibitor of PAK4 and NAMPT, in Patients with Advanced Solid Malignancies. Target Oncol. 2026 Mar;21(2):187-198. doi: 10.1007/s11523-026-01206-3. Epub 2026 Mar 13. | |
| 37864885 |
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A total of 60 participants were enrolled and randomized to receive treatment in 2 phases, Dose Escalation (Part A [23 participants] and Part B [27 participants]; and Dose Expansion Phases (Part C [10 participants]). Study was terminated prematurely due to a lack of efficacy during primary analysis and therefore, efficacy, pharmacokinetic (PK) and pharmacodynamics (PDn) assessments were not determined.
This study was conducted at 8 investigative sites in the United States and Canada from 08 Jun 2016 to 26 Jan 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: KPT-9274 10mg | Participants received 10 milligrams (mg) of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| FG001 | Part A: KPT-9274 20mg | Participants received 20mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| FG002 | Part A: KPT-9274 30mg | Participants received 30mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| FG003 | Part A: KPT-9274 40mg | Participants received 40mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| FG004 | Part A: KPT-9274 40mg BIW | Participants received KPT-9274 40mg of oral tablet biweekly (BIW) during each 28-day cycle. |
| FG005 | Part B: KPT-9274 30mg + Niacin 500mg | Participants received KPT-9274 30mg of oral tablet along with a starting dose of 500mg niacin extended release (ER) orally three times a week every other day during each 28-day cycle |
| FG006 | Part B: KPT-9274 40mg + Niacin 500mg | Participants received KPT-9274 40mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle |
| FG007 | Part B: KPT-9274 60mg + Niacin 500mg | Participants received KPT-9274 60mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle |
| FG008 | Part B: KPT-9274 80mg + Niacin 500mg | Participants received KPT-9274 80mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle |
| FG009 | Part B: KPT-9274 100mg + Niacin 500mg | Participants received KPT-9274 100mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle |
| FG010 | Part C: KPT-9274 20mg + Nivolumab 480mg | Participants received KPT-9274 20mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| FG011 | Part C: KPT-9274 30mg + Nivolumab 480mg | Participants received KPT-9274 30mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| FG012 | Part C: KPT-9274 40mg + Nivolumab 480mg | Participants received KPT-9274 40mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety population consisted of all participants who had received at least 1 dose of the study treatment. Participants were analyzed according to the treatment they received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: KPT-9274 10mg | Participants received 10mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| BG001 | Part A: KPT-9274 20mg | Participants received 20mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Maximum Tolerated Dose (MTD) for KPT-9274 | The MTD was defined as the highest dose at which less than or equal to (<=) 1 participant experienced a dose limiting toxicity (DLT) in Cycle 1. A DLT was defined as an adverse event (AE) or abnormal laboratory value occurring within the first 28 days of treatment of KPT-9274, excluding those clearly caused by underlying disease, disease progression, or external factors. | Study was terminated prematurely due to a lack of efficacy. Therefore, the data were not determined due to insufficient number of participants with events. | Posted | Count of Participants | Participants | From start of study drug administration up to 44 weeks |
|
From start of study drug administration up to 49 weeks
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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 | Part A: KPT-9274 10mg | Participants received 10 milligrams (mg) of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 23.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 23.1 | Systematic Assessment |
Study was terminated prematurely due to a lack of efficacy during primary analysis and therefore, efficacy, PK and PDn assessments were not determined.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Karyopharm Medical Information | Karyopharm Therapeutics Inc | (888) 209-9326 | clinicaltrials@karyopharm.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 11, 2020 | Aug 17, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 8, 2021 | Aug 17, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C000622300 | KPT-9274 |
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Experimental |
Participants received KPT-9274 30mg of oral tablet along with a starting dose of 500mg niacin extended release (ER) orally three times a week every other day during each 28-day cycle. |
|
| Part B: KPT-9274 40mg + Niacin 500mg | Experimental | Participants received KPT-9274 40mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
|
| Part B: KPT-9274 60mg + Niacin 500mg | Experimental | Participants received KPT-9274 60mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
|
| Part B: KPT-9274 80mg + Niacin 500mg | Experimental | Participants received KPT-9274 80mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
|
| Part B: KPT-9274 100mg + Niacin 500mg | Experimental | Participants received KPT-9274 100mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
|
| Part C: KPT-9274 20mg + Nivolumab 480mg | Experimental | Participants received KPT-9274 20mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
|
| Part C: KPT-9274 30mg + Nivolumab 480mg | Experimental | Participants received KPT-9274 30mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
|
| Part C: KPT-9274 40mg + Nivolumab 480mg | Experimental | Participants received KPT-9274 40mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
|
| Niacin ER | Drug |
|
| Nivolumab | Drug |
|
|
| From date of randomization up to 44 weeks |
| Percentage of Participants With Disease Control Rate (DCR) | The DCR was defined as percentage of participants who have a response of CR, PR, and stable disease (SD) >= 16 weeks, DCR = CR + PR+ SD. The PR was achieved when a participant had at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The CR was achieved in a participant when all target lesions disappeared. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10mm. The SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). | From date of the first study treatment up to 44 weeks |
| Progression-free Survival (PFS) | The PFS was defined as the duration of time from date of the first study treatment until the first date that PD is objectively documented or death due to any cause. The PD is defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Appearance of one or more new lesions will also constitute PD. | From the date of first study treatment until the first date of PD, or death due (up to 44 weeks) |
| Overall Survival (OS) | The OS was defined as the duration of time from date of the first study treatment until death from any cause. | From date of the first study treatment until death (up to 44 weeks) |
| Time to Progression (TTP) | The TTP was defined as the duration of time from date of the first study treatment until the first date that PD was objectively documented or death due to PD. | From date of the first study treatment until the first date of PD or death (up to 44 weeks) |
| Duration of Response (DOR) | The DOR was defined as the duration of time from the first meeting CR or PR measurement criteria (whichever occurs first) until the first date diseases progression. | Up to 44 weeks |
Time taken by KPT-9274 to achieve maximum plasma concentration after the first dose administration. |
| Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
| Terminal Half-life (T1/2) in Participants Who Received KPT-9274 | The T1/2 was defied as the time it takes for the concentration of KPT-9274 in the plasma to be reduced by 50%. | Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
| Volume of Distribution (Vd/F) in Participants Who Received KPT-9274 | The Vd/F was defined as MRT*CL/F, where MRT is the mean residence time (calculated as AUMC[0-tau]/AUC[0-tau], where AUMC[0-tau] is the area under the first moment curve determined as the area under the concentration*time versus time curve). | Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
| Apparent Plasma Clearance (CL/F) in Participants Who Received KPT-9274 | The CL/F was calculated as the KPT-9274 dose administered divided by the area-under-the-curve of KPT-9274 plasma concentration versus (vs) time. | Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Georgetown University, Lombardi Comprehensive Cancer Center | Washington D.C. | District of Columbia | 20007 | United States |
| Mayo Clinic Rochester | Rochester | Minnesota | 55905 | United States |
| NYU-Laura & Isaac Perlmutter Cancer Center | New York | New York | 100016 | United States |
| Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | 37232 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| Han W, Yang Y, Yu F, Li Q, Liu A, Xu W, Li J, Xue X. Design, synthesis and anticancer activity evaluation of 4-(3-1H-indazolyl)amino quinazoline derivatives as PAK4 inhibitors. Bioorg Med Chem. 2023 Nov 15;95:117501. doi: 10.1016/j.bmc.2023.117501. Epub 2023 Oct 13. |
| 34253597 | Derived | Mpilla GB, Uddin MH, Al-Hallak MN, Aboukameel A, Li Y, Kim SH, Beydoun R, Dyson G, Baloglu E, Senapedis WT, Landesman Y, Wagner KU, Viola NT, El-Rayes BF, Philip PA, Mohammad RM, Azmi AS. PAK4-NAMPT Dual Inhibition Sensitizes Pancreatic Neuroendocrine Tumors to Everolimus. Mol Cancer Ther. 2021 Oct;20(10):1836-1845. doi: 10.1158/1535-7163.MCT-20-1105. Epub 2021 Jul 12. |
| 28062705 | Derived | Aboukameel A, Muqbil I, Senapedis W, Baloglu E, Landesman Y, Shacham S, Kauffman M, Philip PA, Mohammad RM, Azmi AS. Novel p21-Activated Kinase 4 (PAK4) Allosteric Modulators Overcome Drug Resistance and Stemness in Pancreatic Ductal Adenocarcinoma. Mol Cancer Ther. 2017 Jan;16(1):76-87. doi: 10.1158/1535-7163.MCT-16-0205. Epub 2016 Nov 15. |
| Clinical progression |
|
| Adverse Event |
|
| Other |
|
| BG002 | Part A: KPT-9274 30mg | Participants received 30mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| BG003 | Part A: KPT-9274 40mg | Participants received 40mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| BG004 | Part A: KPT-9274 40mg BIW | Participants received KPT-9274 40mg of oral tablet BIW during each 28-day cycle. |
| BG005 | Part B: KPT-9274 30mg + Niacin 500mg | Participants received KPT-9274 30mg of oral tablet along with a starting dose of 500mg niacin extended release (ER) orally three times a week every other day during each 28-day cycle. |
| BG006 | Part B: KPT-9274 40mg + Niacin 500mg | Participants received KPT-9274 40mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| BG007 | Part B: KPT-9274 60mg + Niacin 500mg | Participants received KPT-9274 60mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| BG008 | Part B: KPT-9274 80mg + Niacin 500mg | Participants received KPT-9274 80mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| BG009 | Part B: KPT-9274 100mg + Niacin 500mg | Participants received KPT-9274 100mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle |
| BG010 | Part C: KPT-9274 20mg + Nivolumab 480mg | Participants received KPT-9274 20mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| BG011 | Part C: KPT-9274 30mg + Nivolumab 480mg | Participants received KPT-9274 30mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| BG012 | Part C: KPT-9274 40mg + Nivolumab 480mg | Participants received KPT-9274 40mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| BG013 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Part A: KPT-9274 20mg | Participants received 20mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| OG002 | Part A: KPT-9274 30mg | Participants received 30mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| OG003 | Part A: KPT-9274 40mg | Participants received 40mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. |
| OG004 | Part A: KPT-9274 40mg BIW | Participants received KPT-9274 40mg of oral tablet biweekly (BIW) during each 28-day cycle. |
| OG005 | Part B: KPT-9274 30mg + Niacin 500mg | Participants received KPT-9274 30mg of oral tablet along with a starting dose of 500mg niacin extended release (ER) orally three times a week every other day during each 28-day cycle. |
| OG006 | Part B: KPT-9274 40mg + Niacin 500mg | Participants received KPT-9274 40mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| OG007 | Part B: KPT-9274 60mg + Niacin 500mg | Participants received KPT-9274 60mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| OG008 | Part B: KPT-9274 80mg + Niacin 500mg | Participants received KPT-9274 80mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| OG009 | Part B: KPT-9274 100mg + Niacin 500mg | Participants received KPT-9274 100mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. |
| OG010 | Part C: KPT-9274 20mg + Nivolumab 480mg | Participants received KPT-9274 20mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| OG011 | Part C: KPT-9274 30mg + Nivolumab 480mg | Participants received KPT-9274 30mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
| OG012 | Part C: KPT-9274 40mg + Nivolumab 480mg | Participants received KPT-9274 40mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). |
|
|
| Primary | Number of Dose Limiting Toxicities (DLT) Experienced by Participants | A DLT was defined as an AE or abnormal laboratory value occurring within the first 28 days of KPT-9274 treatment, excluding those clearly caused by underlying disease, disease progression, or extraneous causes, and meets any of the criteria for defining dose limiting toxicities. | The safety population consisted of all participants who had received at least 1 dose of the study treatment. | Posted | Number | Number of DLTs | At Cycle 1 only (28-day cycle) |
|
|
|
| Primary | Number of Participants With Adverse Event (AE) of Severity Grade >= 3 or 4, Serious AEs, and AEs Leading to Treatment Discontinuation | The AE severity was graded on a scale from 1 to 4 using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03; any events not specifically listed in the scale were defined as: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening. An SAE was any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. The AE leading to treatment discontinuation in the study. | The safety population consisted of all participants who had received at least 1 dose of the study treatment. | Posted | Count of Participants | Participants | From start of study drug administration up to 49 weeks |
|
|
|
| Primary | Percentage of Participants With Overall Response Rate (ORR) | The ORR was defined as percentage of participants who had a response of partial response (PR) or complete response (CR). The PR was achieved when a participant had at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The CR was achieved in a participant when all target lesions disappeared. Any pathological lymph nodes (whether target or non target) must have reduction in the short axis to <10 millimeter (mm). | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | From date of randomization up to 44 weeks |
|
|
| Primary | Percentage of Participants With Disease Control Rate (DCR) | The DCR was defined as percentage of participants who have a response of CR, PR, and stable disease (SD) >= 16 weeks, DCR = CR + PR+ SD. The PR was achieved when a participant had at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The CR was achieved in a participant when all target lesions disappeared. Any pathological lymph nodes (whether target or non-target) must have reduction in the short axis to <10mm. The SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | From date of the first study treatment up to 44 weeks |
|
|
| Primary | Progression-free Survival (PFS) | The PFS was defined as the duration of time from date of the first study treatment until the first date that PD is objectively documented or death due to any cause. The PD is defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Appearance of one or more new lesions will also constitute PD. | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | From the date of first study treatment until the first date of PD, or death due (up to 44 weeks) |
|
|
| Primary | Overall Survival (OS) | The OS was defined as the duration of time from date of the first study treatment until death from any cause. | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | From date of the first study treatment until death (up to 44 weeks) |
|
|
| Primary | Time to Progression (TTP) | The TTP was defined as the duration of time from date of the first study treatment until the first date that PD was objectively documented or death due to PD. | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | From date of the first study treatment until the first date of PD or death (up to 44 weeks) |
|
|
| Primary | Duration of Response (DOR) | The DOR was defined as the duration of time from the first meeting CR or PR measurement criteria (whichever occurs first) until the first date diseases progression. | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | Up to 44 weeks |
|
|
| Secondary | Maximum Plasma Concentration (Cmax) in Participants Who Received KPT-9274 | Cmax achieved by the KPT-9274 after the first dose administrations. | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
|
|
| Secondary | Time-to-peak Plasma Concentration (Tmax) in Participants Who Received KPT-9274 | Time taken by KPT-9274 to achieve maximum plasma concentration after the first dose administration. | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
|
|
| Secondary | Terminal Half-life (T1/2) in Participants Who Received KPT-9274 | The T1/2 was defied as the time it takes for the concentration of KPT-9274 in the plasma to be reduced by 50%. | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
|
|
| Secondary | Volume of Distribution (Vd/F) in Participants Who Received KPT-9274 | The Vd/F was defined as MRT*CL/F, where MRT is the mean residence time (calculated as AUMC[0-tau]/AUC[0-tau], where AUMC[0-tau] is the area under the first moment curve determined as the area under the concentration*time versus time curve). | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
|
|
| Secondary | Apparent Plasma Clearance (CL/F) in Participants Who Received KPT-9274 | The CL/F was calculated as the KPT-9274 dose administered divided by the area-under-the-curve of KPT-9274 plasma concentration versus (vs) time. | Study was terminated prematurely due to a lack of efficacy during primary analysis stage. Data for this outcome measure was not collected or analyzed as per planned analysis. | Posted | Cycle 1 and 2: Pre-dose, 3, 6, 8, 24, and 48 hours post-dose (each cycle =28 days) |
|
|
| 2 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | Part A: KPT-9274 20mg | Participants received 20mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. | 2 | 3 | 2 | 3 | 2 | 3 |
| EG002 | Part A: KPT-9274 30mg | Participants received 30mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. | 3 | 5 | 2 | 5 | 5 | 5 |
| EG003 | Part A: KPT-9274 40mg | Participants received 40mg of oral tablets of KPT-9274 three times a week every other day during each 28 day cycle. | 5 | 7 | 3 | 7 | 7 | 7 |
| EG004 | Part A: KPT-9274 40mg BIW | Participants received KPT-9274 40mg of oral tablet biweekly (BIW) during each 28-day cycle. | 1 | 5 | 0 | 5 | 5 | 5 |
| EG005 | Part B: KPT-9274 30mg + Niacin 500mg | Participants received KPT-9274 30mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. | 3 | 3 | 1 | 3 | 3 | 3 |
| EG006 | Part B: KPT-9274 40mg + Niacin 500mg | Participants received KPT-9274 40mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. | 3 | 4 | 1 | 4 | 4 | 4 |
| EG007 | Part B: KPT-9274 60mg + Niacin 500mg | Participants received KPT-9274 60mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. | 6 | 12 | 6 | 12 | 12 | 12 |
| EG008 | Part B: KPT-9274 80mg + Niacin 500mg | Participants received KPT-9274 80mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. | 4 | 7 | 1 | 7 | 7 | 7 |
| EG009 | Experimental: Part B: KPT-9274 100mg + Niacin 500mg | Participants received KPT-9274 100mg of oral tablet along with a starting dose of 500mg niacin ER orally three times a week every other day during each 28-day cycle. | 1 | 1 | 1 | 1 | 1 | 1 |
| EG010 | Part C: KPT-9274 20mg + Nivolumab 480mg | Participants received KPT-9274 20mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). | 1 | 1 | 1 | 1 | 1 | 1 |
| EG011 | Part C: KPT-9274 30mg + Nivolumab 480mg | Participants received KPT-9274 30mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). | 2 | 5 | 2 | 5 | 5 | 5 |
| EG012 | Part C: KPT-9274 40mg + Nivolumab 480mg | Participants received KPT-9274 40mg of oral tablet three times a week every other day during each 28-day cycle along with 480mg of nivolumab intravenous infusion on Day 1 of each cycle (once every 4-week cycle). | 3 | 4 | 2 | 4 | 4 | 4 |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Death | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Klebsiella bacteraemia | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Cardiac murmur | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 23.1 | Systematic Assessment |
|
| Intracranial mass | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Campylobacter infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Clostridium difficile infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Clostridium difficile infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Wound infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypercreatininaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Skin burning sensation | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Anaemia of malignant disease | Blood and lymphatic system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Pupils unequal | Eye disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Anal incontinence | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hepatic vein thrombosis | Hepatobiliary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA version 23.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Blood iron decreased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Blood thyroid stimulating hormone increased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Reticulocyte count decreased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hyperamylasaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Myoclonus | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Nystagmus | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Irritability | Psychiatric disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Lymphoedema | Vascular disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Cardiomegaly | Cardiac disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Abdominal infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Campylobacter infection | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Escherichia bacteraemia | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Lyme disease | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA version 23.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA version 23.1 | Systematic Assessment |
|
| Incision site pain | Injury, poisoning and procedural complications | MedDRA version 23.1 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA version 23.1 | Systematic Assessment |
|
| Wound dehiscence | Injury, poisoning and procedural complications | MedDRA version 23.1 | Systematic Assessment |
|
| Vitamin B12 decreased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Glucose urine present | Investigations | MedDRA version 23.1 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 23.1 | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Generalised oedema | Gastrointestinal disorders | MedDRA version 23.1 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA version 23.1 | Systematic Assessment |
|
Not provided
Not provided
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Maximum Grade 4 AEs |
|
| Serious AEs |
|
| AEs Leading to Study Treatment Discontinuation |
|