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Sponsor decision
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The purpose of this study is to evaluate the efficacy and safety of selinexor alone or with pembrolizumab in participants with advanced or metastatic colorectal cancer (CRC). Approximately 78 participants with advanced or metastatic CRC will be enrolled, and randomized (1:1:1) into three arms A (selinexor only), B (selinexor and pembrolizumab), and C (standard of care [Combination of trifluridine and tipiracil]). Randomization will be based on stratification factors: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 versus 2. The end of treatment (EoT) visit will occur less than or equal to (<=30) days post-treatment discontinuation. A survival follow-up visit will be performed every 3 months from EoT and will continue for 12 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Selinexor 80 mg | Experimental | Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 33 weeks). |
|
| Arm B: Selinexor 80 mg and Pembrolizumab 400 mg | Experimental | Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) in combination with pembrolizumab 400 mg IV once every 6 weeks of each 42-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 30 weeks). |
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| Arm C: Standard of care (SOC) | Active Comparator | Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Selinexor | Drug | Participants will receive selinexor oral tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Arm B and C: Progression-free Survival (PFS) as Assessed by the Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | PFS was defined as the time from the date of randomization until disease progression or death due to any cause, whichever occurs first. PFS was assessed by the investigator per RECIST 1.1. As per RECIST 1.1 criteria, PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions. | From the date of randomization until disease progression or death, whichever occurs first (up to 8 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Arm A, B and C: Overall Survival (OS) | OS was defined as time from the date of randomization to death due to any cause. | From the date of randomization up to death (up to 8 months) |
| Arm B and C: Overall Response Rate (ORR) |
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Inclusion Criteria:
Exclusion Criteria:
Prior treatment with a selective inhibitor of nuclear export (SINE) compound or selinexor.
Prior treatment with immune checkpoint inhibitors.
Participants with microsatellite instability high (MSI-H) or deficient mismatch repair (dMMR).
Known allergy to any of study drugs (selinexor, pembrolizumab, and trifluridine and tipiracil) or the excipient of pembrolizumab.
Significant cardiovascular impairment, defined as:
Impaired hematopoietic function (any of the following would result in exclusion):
Significant renal impairment, defined as: calculated creatinine clearance (CrCl) of < 30 milliliter per minute (mL/min) using the formula of Cockcroft and Gault.
Impaired hepatic function defined as: total bilirubin greater than (>) 1.5 × upper limit of normal (ULN) and aspartate transaminase (AST) > 2.5 x ULN, AST > 2.5 x ULN; for Arm B, unless bilirubin elevation is related to Gilbert's Syndrome for which bilirubin must be ≤ 4 x ULN.
Participants with a diagnosis of immunodeficiency or are receiving systemic steroid therapy (>10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy. Participants with active autoimmune disease requiring systemic treatment during the past 2 years.
Note: The Investigator needs to evaluate the participants medical history to confirm that they are eligible to receive the combination with pembrolizumab per these criteria.
Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as:
Female participants who are pregnant or lactating.
Active, ongoing or uncontrolled active infection requiring parenteral antibiotics, antivirals, antifungals within 1 week of Screening.
Participants with autoimmune disease, a medical condition that requires systemic corticosteroids or other immunosuppressive medication; or a history of interstitial lung disease.
Any gastrointestinal dysfunctions that could interfere with the absorption of selinexor (e.g. bowel obstruction, inability to swallow tablets, malabsorption syndrome, unresolved nausea, vomiting, diarrhea CTCAE > grade 1).
In the opinion of the investigator, participants who are below their ideal body weight and would be unduly impacted by changes in their weight.
Serious psychiatric or medical conditions that could interfere with participation in the study or in the opinion of the Investigator would make study involvement unreasonably hazardous.
Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Valkyrie Clinical Trials | Los Angeles | California | 90067 | United States | ||
| Christiana Care Health Services, Christiana Hospital |
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A total of 13 participants were enrolled and randomized to receive study treatments Arm A (single-agent selinexor), Arm B (selinexor + pembrolizumab), or Arm C (standard of care) based on the stratification factor of Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 versus 2.
The study was conducted at 3 investigational sites in the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Selinexor 80 mg | Participants received a single dose of selinexor 80 milligrams (mg); (4 tablets of 20 mg) orally once weekly (QW) on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) until progressive disease (PD), intolerable toxicity, or withdrawal from the study (maximum exposure: 33 weeks). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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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 | May 26, 2021 | Jul 28, 2023 |
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| Pembrolizumab | Drug | Participants will receive pembrolizumab intravenously. |
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| Trifluridine | Drug | Participants will receive trifluridine oral tablets as SOC. |
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| Tipiracil | Drug | Participants will receive tipiracil oral tablets as SOC. |
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ORR was defined as the percentage of participants who achieve complete response (CR) or partial response (PR) or or initiating a new antineoplastic therapy. ORR was assessed by RECIST 1.1 as defined by the Investigator based on radiologic criteria. Per RECIST 1.1 criteria, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
| From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 8 months) |
| Arm A and C: Overall Response Rate (ORR) | ORR was defined as the percentage of participants who achieve CR or PR or or initiating a new antineoplastic therapy. ORR was assessed by RECIST 1.1 as defined by the Investigator based on radiologic criteria. Per RECIST 1.1 criteria, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 8 months) |
| Arm A, B and C: Progression-free Survival (PFS) at 6 Months | PFS at 6 months was defined as the time from the date of randomization without disease progression at 6 months as assessed by the investigator per RECIST 1.1. As per RECIST 1.1 criteria, PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. | At 6 Months |
| Arm A, B and C: Percentage of Participants With Overall Survival (OS) at 6 Months | OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at 6 months. | At 6 Months |
| Arm A, B and C: Percentage of Participants With Overall Survival (OS) at 12 Months | OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at 12 months. | At 12 Months |
| Arm B and C: Duration of Response (DOR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 | DOR was defined as the time from first occurrence of CR or PR until the first date of PD per RECIST version 1.1 or death. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From first occurrence of CR or PR until disease progression or death, whichever occurs first (up to 8 months) |
| Arm A and C: Duration of Response (DOR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 | DOR was defined as the time from first occurrence of CR or PR until the first date of PD per RECIST version 1.1 or death. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From first occurrence of CR or PR until disease progression or death, whichever occurs first (up to 8 months) |
| Arm B and C: Percentage of Participants With Confirmed Disease Control Rate as Per Response Evaluation Criteria in Solid Tumors Version 1.1 | Disease control rate was defined as participants who achieved best overall response of CR, PR, or at least 12 continuous weeks of stable disease (SD) as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1 before PD or initiating a new antineoplastic therapy, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. | From the date of randomization up to death (up to 8 months) |
| Arm A and C: Percentage of Participants With Confirmed Disease Control Rate as Per Response Evaluation Criteria in Solid Tumors Version 1.1 | Disease control rate was defined as participants who achieved best overall response of CR, PR, or at least 12 continuous weeks of stable disease (SD) as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1 before PD or initiating a new antineoplastic therapy, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. | From the date of randomization up to death (up to 8 months) |
| Arm A, B and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. | From start of study drug administration up to 12 months |
| Newark |
| Delaware |
| 19718 |
| United States |
| BRCR Global | Plantation | Florida | 33322 | United States |
| FG001 |
| Arm B: Selinexor 80 mg and Pembrolizumab 400 mg |
Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) in combination with pembrolizumab 400 mg intravenously (IV) once every 6 weeks of each 42-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 30 weeks). |
| FG002 | Arm C: Standard of Care (SOC) | Participants received combination of trifluridine and tipiracil 35 milligrams per square meter per dose (mg/m^2/dose) tablets orally twice daily (BID) (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Selinexor 80 mg | Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 33 weeks). |
| BG001 | Arm B: Selinexor 80 mg and Pembrolizumab 400 mg | Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) in combination with pembrolizumab 400 mg IV once every 6 weeks of each 42-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 30 weeks). |
| BG002 | Arm C: Standard of Care (SOC) | Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | Arm B and C: Progression-free Survival (PFS) as Assessed by the Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | PFS was defined as the time from the date of randomization until disease progression or death due to any cause, whichever occurs first. PFS was assessed by the investigator per RECIST 1.1. As per RECIST 1.1 criteria, PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions. | Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus the colorectal cancer (CRC) program was closed. Data for this outcome measure was not planned to be collected and analyzed for Arm A. | Posted | Median | 95% Confidence Interval | Months | From the date of randomization until disease progression or death, whichever occurs first (up to 8 months) |
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| Secondary | Arm A, B and C: Overall Survival (OS) | OS was defined as time from the date of randomization to death due to any cause. | Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed. | Posted | Median | 95% Confidence Interval | months | From the date of randomization up to death (up to 8 months) |
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| Secondary | Arm B and C: Overall Response Rate (ORR) | ORR was defined as the percentage of participants who achieve complete response (CR) or partial response (PR) or or initiating a new antineoplastic therapy. ORR was assessed by RECIST 1.1 as defined by the Investigator based on radiologic criteria. Per RECIST 1.1 criteria, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | ITT population included all participants randomized to study treatment and were analyzed in the treatment arm to which they were randomized. Data for this outcome measure was not planned to be collected and analyzed for Arm A. | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 8 months) |
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| Secondary | Arm A and C: Overall Response Rate (ORR) | ORR was defined as the percentage of participants who achieve CR or PR or or initiating a new antineoplastic therapy. ORR was assessed by RECIST 1.1 as defined by the Investigator based on radiologic criteria. Per RECIST 1.1 criteria, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | ITT population included all participants randomized to study treatment and were analyzed in the treatment arm to which they were randomized. Data for this outcome measure was not planned to be collected and analyzed for Arm B. | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 8 months) |
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| Secondary | Arm A, B and C: Progression-free Survival (PFS) at 6 Months | PFS at 6 months was defined as the time from the date of randomization without disease progression at 6 months as assessed by the investigator per RECIST 1.1. As per RECIST 1.1 criteria, PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. | Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed. | Posted | Median | 95% Confidence Interval | months | At 6 Months |
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| Secondary | Arm A, B and C: Percentage of Participants With Overall Survival (OS) at 6 Months | OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at 6 months. | Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed. | Posted | Median | 95% Confidence Interval | percentage of event free participants | At 6 Months |
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| Secondary | Arm A, B and C: Percentage of Participants With Overall Survival (OS) at 12 Months | OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at 12 months. | Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed. | Posted | Median | 95% Confidence Interval | percentage of event free participants | At 12 Months |
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| Secondary | Arm B and C: Duration of Response (DOR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 | DOR was defined as the time from first occurrence of CR or PR until the first date of PD per RECIST version 1.1 or death. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | ITT population included all participants randomized to study treatment and were analyzed in the treatment arm to which they were randomized. Here, "overall number of participants analyzed" signifies those who had response (CR/PR) in specified arm. Data for this outcome measure was not planned to be collected and analyzed for Arm A. | Posted | From first occurrence of CR or PR until disease progression or death, whichever occurs first (up to 8 months) |
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| Secondary | Arm A and C: Duration of Response (DOR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 | DOR was defined as the time from first occurrence of CR or PR until the first date of PD per RECIST version 1.1 or death. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | ITT population included all participants randomized to study treatment and were analyzed in the treatment arm to which they were randomized. Here, "overall number of participants analyzed" signifies those who had response (CR/PR) in specified arm. Data for this outcome measure was not planned to be collected and analyzed for Arm B. | Posted | Median | 95% Confidence Interval | months | From first occurrence of CR or PR until disease progression or death, whichever occurs first (up to 8 months) |
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| Secondary | Arm B and C: Percentage of Participants With Confirmed Disease Control Rate as Per Response Evaluation Criteria in Solid Tumors Version 1.1 | Disease control rate was defined as participants who achieved best overall response of CR, PR, or at least 12 continuous weeks of stable disease (SD) as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1 before PD or initiating a new antineoplastic therapy, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. | ITT population included all participants randomized to study treatment and were analyzed in the treatment arm to which they were randomized. Here, "overall number of participants analyzed" signifies those who had response (CR/PR/SD) in specified arm. Data for this outcome measure was not planned to be collected and analyzed for Arm A. | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of randomization up to death (up to 8 months) |
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| Secondary | Arm A and C: Percentage of Participants With Confirmed Disease Control Rate as Per Response Evaluation Criteria in Solid Tumors Version 1.1 | Disease control rate was defined as participants who achieved best overall response of CR, PR, or at least 12 continuous weeks of stable disease (SD) as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1 before PD or initiating a new antineoplastic therapy, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. | ITT population included all participants randomized to study treatment and were analyzed in the treatment arm to which they were randomized. Here, "overall number of participants analyzed" signifies those who had response (CR/PR/SD) in specified arm. Data for this outcome measure was not planned to be collected and analyzed for Arm B. | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of randomization up to death (up to 8 months) |
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| Secondary | Arm A, B and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. | Safety population included all participants who were assigned to study treatment and who received greater than or equal to 1 dose of study drug. | Posted | Count of Participants | Participants | From start of study drug administration up to 12 months |
|
From start of study drug administration up to 12 months
Analysis was performed on safety population.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: Selinexor 80 mg | Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 33 weeks). | 1 | 4 | 1 | 4 | 4 | 4 |
| EG001 | Arm B: Selinexor 80 mg and Pembrolizumab 400 mg | Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) in combination with pembrolizumab 400 mg IV once every 6 weeks of each 42-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 30 weeks). | 3 | 5 | 2 | 5 | 5 | 5 |
| EG002 | Arm C: Standard of Care (SOC) | Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). | 4 | 4 | 0 | 4 | 4 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 24.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Androgen deficiency | Endocrine disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Anal inflammation | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Gastric haemorrhage | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Temperature intolerance | General disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 24.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 24.1 | Non-systematic Assessment |
| |
| Urinary tract infection staphylococcal | Infections and infestations | MedDRA 24.1 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 24.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 24.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 24.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 24.1 | Non-systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA 24.1 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 24.1 | Non-systematic Assessment |
| |
| Protein total decreased | Investigations | MedDRA 24.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Hypersomnia | Nervous system disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Nightmare | Psychiatric disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 24.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 24.1 | Non-systematic Assessment |
|
Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed. Thereby some of the protocol planned analysis were not performed and thus no data was reported for those outcome measures.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Karyopharm Medical Information | Karyopharm Therapeutics Inc | (888) 209-9326 | clinicaltrials@karyopharm.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 23, 2023 | Jul 28, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C585161 | selinexor |
| C582435 | pembrolizumab |
| D014271 | Trifluridine |
| C000613754 | tipiracil |
| ID | Term |
|---|---|
| D013936 | Thymidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks).
|
|
|
|
| OG002 | Arm C: Standard of Care (SOC) | Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). |
|
|
Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). |
|
|
Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). |
|
|
|
|
|
| OG001 | Arm C: Standard of Care (SOC) | Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). |
|
|
| OG001 | Arm C: Standard of Care (SOC) | Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). |
|
|
| Arm B: Selinexor 80 mg and Pembrolizumab 400 mg |
Participants received a single dose of selinexor 80 mg (4 tablets of 20 mg) orally QW on Day 1 of each week of a 42-day cycle (i.e., on Days 1, 8, 15, 22, 29, and 36 of each 42-day cycle) in combination with pembrolizumab 400 mg IV once every 6 weeks of each 42-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 30 weeks). |
| OG002 | Arm C: Standard of Care (SOC) | Participants received combination of trifluridine and tipiracil 35 mg/m^2/dose tablets orally BID (maximum 80 mg per dose) as SOC on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until PD, intolerable toxicity, or withdrawal from the study (maximum exposure: 11 weeks). |
|
|