Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of Selinexor With or Without Pembrolizumab Versus Standard of Care in Previously Treated Metastatic Colorectal Cancer With RAS Mutations (NCT NCT04854434)

Last Updated: 2023-11-03

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

From the date of randomization until disease progression or death, whichever occurs first (up to 8 months)

Results posted on

2023-11-03

Participant Flow

The study was conducted at 3 investigational sites in the United States.

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.

Participant milestones

Participant milestones
Measure	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).	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).	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).
Overall Study STARTED	4	5	4
Overall Study COMPLETED	0	1	0
Overall Study NOT COMPLETED	4	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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).	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).
Overall Study Death	1	3	4
Overall Study Study Terminated by Sponsor	2	0	0
Overall Study Other	1	1	0

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of Selinexor With or Without Pembrolizumab Versus Standard of Care in Previously Treated Metastatic Colorectal Cancer With RAS Mutations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Selinexor 80 mg n=4 Participants 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 n=5 Participants 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).	Arm C: Standard of Care (SOC) n=4 Participants 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).	Total n=13 Participants Total of all reporting groups
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Continuous	70.5 years STANDARD_DEVIATION 3.11 • n=93 Participants	61.0 years STANDARD_DEVIATION 14.78 • n=4 Participants	57.0 years STANDARD_DEVIATION 17.63 • n=27 Participants	62.7 years STANDARD_DEVIATION 13.61 • n=483 Participants
Sex: Female, Male Female	1 Participants n=93 Participants	4 Participants n=4 Participants	1 Participants n=27 Participants	6 Participants n=483 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants	7 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=93 Participants	5 Participants n=4 Participants	2 Participants n=27 Participants	10 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants	5 Participants n=4 Participants	4 Participants n=27 Participants	12 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants

PRIMARY outcome

Timeframe: From the date of randomization until disease progression or death, whichever occurs first (up to 8 months)

Population: 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.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=5 Participants 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).	Arm C: Standard of Care (SOC) n=4 Participants 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 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 and C: Progression-free Survival (PFS) as Assessed by the Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	NA Months Median PFS and 95% CI was not available due to insufficient numbers of participants with events.	NA Months Median PFS and 95% CI was not available due to insufficient numbers of participants with events.	—

SECONDARY outcome

Timeframe: From the date of randomization up to death (up to 8 months)

Population: Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed.

OS was defined as time from the date of randomization to death due to any cause.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=4 Participants 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).	Arm C: Standard of Care (SOC) n=5 Participants 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 C: Standard of Care (SOC) n=4 Participants 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 A, B and C: Overall Survival (OS)	NA months Median and 95% CI was not available due to insufficient numbers of participants with events.	NA months Median and 95% CI was not available due to insufficient numbers of participants with events.	NA months Median and 95% CI was not available due to insufficient numbers of participants with events.

SECONDARY outcome

Timeframe: From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 8 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=5 Participants 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).	Arm C: Standard of Care (SOC) n=4 Participants 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 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 and C: Overall Response Rate (ORR)	0 percentage of participants Lower limit and upper limit of 95% confidence interval was not available because no participant had CR/PR event.	0 percentage of participants Lower limit and upper limit of 95% confidence interval was not available because no participant had CR/PR event.	—

SECONDARY outcome

Timeframe: From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 8 months)

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.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=4 Participants 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).	Arm C: Standard of Care (SOC) n=4 Participants 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 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 A and C: Overall Response Rate (ORR)	25.0 percentage of participants Interval 0.6 to 80.6	0 percentage of participants Lower limit and upper limit of 95% confidence interval was not available because no participant had CR/PR event.	—

SECONDARY outcome

Timeframe: At 6 Months

Population: Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed.

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.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=4 Participants 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).	Arm C: Standard of Care (SOC) n=5 Participants 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 C: Standard of Care (SOC) n=4 Participants 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 A, B and C: Progression-free Survival (PFS) at 6 Months	NA months Median PFS and 95% CI was not available due to insufficient numbers of participants with events.	NA months Median PFS and 95% CI was not available due to insufficient numbers of participants with events.	NA months Median PFS and 95% CI was not available due to insufficient numbers of participants with events.

SECONDARY outcome

Timeframe: At 6 Months

Population: Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed.

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.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=4 Participants 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).	Arm C: Standard of Care (SOC) n=5 Participants 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 C: Standard of Care (SOC) n=4 Participants 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 A, B and C: Percentage of Participants With Overall Survival (OS) at 6 Months	NA percentage of event free participants Median and 95% CI was not available due to insufficient numbers of participants with events.	NA percentage of event free participants Median and 95% CI was not available due to insufficient numbers of participants with events.	NA percentage of event free participants Median and 95% CI was not available due to insufficient numbers of participants with events.

SECONDARY outcome

Timeframe: At 12 Months

Population: Prior to study completion, the signal was assessed by sponsor to be uncompetitive in the current treatment landscape and thus CRC program was closed.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=4 Participants 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).	Arm C: Standard of Care (SOC) n=5 Participants 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 C: Standard of Care (SOC) n=4 Participants 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 A, B and C: Percentage of Participants With Overall Survival (OS) at 12 Months	NA percentage of event free participants Median and 95% CI was not available due to insufficient numbers of participants with events.	NA percentage of event free participants Median and 95% CI was not available due to insufficient numbers of participants with events.	NA percentage of event free participants Median and 95% CI was not available due to insufficient numbers of participants with events.

SECONDARY outcome

Timeframe: From first occurrence of CR or PR until disease progression or death, whichever occurs first (up to 8 months)

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first occurrence of CR or PR until disease progression or death, whichever occurs first (up to 8 months)

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=1 Participants 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).	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 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 A and C: Duration of Response (DOR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1	NA months Median and 95% CI was not estimable due to single participant.	—	—

SECONDARY outcome

Timeframe: From the date of randomization up to death (up to 8 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=5 Participants 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).	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 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 and C: Percentage of Participants With Confirmed Disease Control Rate as Per Response Evaluation Criteria in Solid Tumors Version 1.1	40.0 percentage of participants Interval 5.3 to 85.3	—	—

SECONDARY outcome

Timeframe: From the date of randomization up to death (up to 8 months)

Population: 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.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=4 Participants 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).	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 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 A and C: Percentage of Participants With Confirmed Disease Control Rate as Per Response Evaluation Criteria in Solid Tumors Version 1.1	100 percentage of participants Lower limit and upper limit of 95% confidence interval was not available because all participants had CR/PR/SD event.	—	—

SECONDARY outcome

Timeframe: From start of study drug administration up to 12 months

Population: Safety population included all participants who were assigned to study treatment and who received greater than or equal to 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Arm B: Selinexor 80 mg and Pembrolizumab 400 mg n=4 Participants 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).	Arm C: Standard of Care (SOC) n=5 Participants 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 C: Standard of Care (SOC) n=4 Participants 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 A, B and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	4 Participants	5 Participants	4 Participants
Arm A, B and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with Serious TEAEs	1 Participants	2 Participants	0 Participants

Adverse Events

Arm A: Selinexor 80 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 1 deaths

Arm B: Selinexor 80 mg and Pembrolizumab 400 mg

Serious events: 2 serious events

Other events: 5 other events

Deaths: 3 deaths

Arm C: Standard of Care (SOC)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Arm A: Selinexor 80 mg n=4 participants at risk 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 n=5 participants at risk 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).	Arm C: Standard of Care (SOC) n=4 participants at risk 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).
Blood and lymphatic system disorders Anaemia	25.0% 1/4 • From start of study drug administration up to 12 months Analysis was performed on safety population.	0.00% 0/5 • From start of study drug administration up to 12 months Analysis was performed on safety population.	0.00% 0/4 • From start of study drug administration up to 12 months Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/4 • From start of study drug administration up to 12 months Analysis was performed on safety population.	20.0% 1/5 • From start of study drug administration up to 12 months Analysis was performed on safety population.	0.00% 0/4 • From start of study drug administration up to 12 months Analysis was performed on safety population.
Injury, poisoning and procedural complications Fall	0.00% 0/4 • From start of study drug administration up to 12 months Analysis was performed on safety population.	20.0% 1/5 • From start of study drug administration up to 12 months Analysis was performed on safety population.	0.00% 0/4 • From start of study drug administration up to 12 months Analysis was performed on safety population.

Other adverse events

Additional Information

Karyopharm Medical Information

Karyopharm Therapeutics Inc

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Principal investigator is a sponsor employee
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