Trial Outcomes & Findings for Safety and Efficacy of Selinexor in Combination With Pembrolizumab in Recurrent Advanced Melanoma (NCT NCT04768881)

Last Updated: 2024-08-23

Results Overview

ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR). 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) with reduction in short axis to less than (\<)10 millimeter (mm). PR was defined as at least a 30 percentage (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 24 months)

Results posted on

2024-08-23

Participant Flow

This study was conducted at 13 sites in United States of America from 12 May 2021 to 22 September 2023.

A total of 15 participants were enrolled and received the study treatment. The study was stopped prematurely due to a lack of sufficient anti-tumor signal for the selinexor/pembrolizumab combination treatment in participants with advanced or metastatic melanoma.

Participant milestones

Participant milestones
Measure	Arm A: Primary Resistance to Initial Checkpoint Inhibitor (CPI) Therapy Participants with advanced or metastatic melanoma were primary resistance to initial CPI therapy received a dose of 80 milligrams (mg) (4 tablets of 20 mg) selinexor orally once weekly (QW) and a dose of pembrolizumab 400 mg intravenously (IV) once in every six weeks (Q6W), both on Day 1 of a 6-week cycle (each cycle = 42 days) until progressive disease (PD), intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Overall Study STARTED	9	6
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	9	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Primary Resistance to Initial Checkpoint Inhibitor (CPI) Therapy Participants with advanced or metastatic melanoma were primary resistance to initial CPI therapy received a dose of 80 milligrams (mg) (4 tablets of 20 mg) selinexor orally once weekly (QW) and a dose of pembrolizumab 400 mg intravenously (IV) once in every six weeks (Q6W), both on Day 1 of a 6-week cycle (each cycle = 42 days) until progressive disease (PD), intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Overall Study Completed Study Follow-up	0	2
Overall Study Death	3	2
Overall Study Study Terminated by Sponsor	2	2
Overall Study Withdrawal by Subject	2	0
Overall Study Other	2	0

Baseline Characteristics

Safety and Efficacy of Selinexor in Combination With Pembrolizumab in Recurrent Advanced Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Total n=15 Participants Total of all reporting groups
Age, Continuous	61.4 Years STANDARD_DEVIATION 13.95 • n=5 Participants	53.7 Years STANDARD_DEVIATION 12.40 • n=7 Participants	58.3 Years STANDARD_DEVIATION 13.48 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization until the documentation of CR or PR, whichever occurs first (up to 24 months)

Population: mITT population consisted of all participants who received at least one dose of any study treatment.

Outcome measures

Outcome measures
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Overall Response Rate (ORR) Assessed as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	33.3 Percentage of participants Interval 7.5 to 70.1	16.7 Percentage of participants Interval 0.4 to 64.1

SECONDARY outcome

Timeframe: From the date of randomization until disease progression or death, due to any cause (up to 24 months)

Population: mITT population consisted of all participants who received at least one dose of any study treatment.

PFS was defined as time from date of first treatment to the date of first confirmed progressive disease (PD), assessed by RECIST 1.1 is objectively documented or death due to any cause. 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 A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Progression-free Survival (PFS) as Per RECIST v 1.1	3.75 Months Interval 2.14 to Upper range of 95% CI could not be estimated due to higher number (\>50%) of censored participants.	6.24 Months Interval 2.1 to Upper range of 95% CI could not be estimated due to higher number (\>50%) of censored participants.

SECONDARY outcome

Timeframe: From the date of first study treatment up to death (up to 24 months)

Population: mITT population consisted of all participants who received at least one dose of any study treatment.

OS was defined as the time from date of first study treatment until death due to any cause. If death event did not occur during the follow-up period, the participant was censored at the date of discontinuation from the study (i.e. withdrawal of consent), or date of last participating visit (e.g., a telephone contact with participant status being alive) on or before database cutoff date, whichever occurs first.

Outcome measures

Outcome measures
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Overall Survival (OS)	NA Months Interval 8.31 to Median and upper range of 95% CI could not be estimated due to insufficient number of participants with event	NA Months Interval 13.08 to Median and upper range of 95% CI could not be estimated due to insufficient number of participants with event

SECONDARY outcome

Timeframe: Up to 101 weeks

Population: mITT population consisted of all participants who received at least one dose of any study treatment.

Complete response rate was defined as percentage of participants who had achieved a complete response (CR) per RECIST 1.1. As per RECIST version 1.1, CR was defined as disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduced in the short axis to \<10 mm.

Outcome measures

Outcome measures
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Complete Response Rate (CRR)	22.2 Percentage of participants Interval 2.8 to 60.0	16.7 Percentage of participants Interval 0.4 to 64.1

SECONDARY outcome

Timeframe: From first occurrence of CR or PR until disease progression or death, whichever occurs first (up to 24 months)

Population: mITT population consisted of all participants who received at least one dose of any study treatment. Only those participants who had confirmed response were included in the analysis. Here, "overall number of participants analyzed" signifies those who had response to DOR.

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. Per RECIST 1.1 criteria, CR was defined as disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with 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. 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 A: Primary Resistance to Initial CPI Therapy n=3 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=1 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Duration of Response (DOR) as Per RECIST v 1.1	NA Months Interval 1.61 to Median and upper range of 95% CI could not be estimated due to higher number (\>50%) of censored participants.	NA Months Median and 95% CI could not be estimated due to higher number (100%) of censored participants.

SECONDARY outcome

Timeframe: Up to 24 months

Population: mITT population consisted of all participants who received at least one dose of any study treatment.

Disease control rate was defined as percentage of participants who have a response of CR, PR, or at least 12 continuous weeks of stable disease (SD) 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) with 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. Percentage values were rounded off.

Outcome measures

Outcome measures
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Percentage of Participants With Disease Control Rate (DCR) as Per RECIST v 1.1	44.4 Percentage of participants Interval 13.7 to 78.8	50.0 Percentage of participants Interval 11.8 to 88.2

SECONDARY outcome

Timeframe: From start of the study treatment up to 24 months

Population: Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.

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 serious adverse event (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 A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	9 Participants	6 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with Serious TEAEs	3 Participants	2 Participants

SECONDARY outcome

Timeframe: From start of the study treatment up to 24 months

Population: Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.

Clinical laboratory parameters included clinical chemistry, hematology and urinalysis. Number of participants with clinically significant laboratory abnormalities which were deemed clinically significant by the investigator were reported.

Outcome measures

Outcome measures
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters Clinical Chemistry	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters Hematology	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters Urinalysis	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From start of the study treatment up to 24 months

Population: Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.

Vital signs included body temperature, blood pressure (systolic blood pressure and diastolic blood pressure). Measurements were made after the participant had been resting supine for a minimum of 5 minutes. The clinically significant change assessment was based on investigator's judgment. Number of participants with clinically significant change from baseline in vital signs values were reported.

Outcome measures

Outcome measures
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Number of Participants With Clinically Significant Changes in Vital Signs Systolic Blood Pressure	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Diastolic Blood Pressure	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Body Temperature	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From start of the study treatment up to 24 months

Population: Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.

Number of participants with clinically significant physical examination abnormalities including general appearance, dermatological, head, eyes, ears, nose, throat, respiratory, cardiovascular, abdominal, lymph nodes, musculoskeletal, and neurological examinations. Number of participants with clinically significant physical examination abnormalities which were deemed clinically significant by the investigator were reported.

Outcome measures

Outcome measures
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Number of Participants With Clinically Significant Changes in Physical Examination	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From start of the study treatment up to 24 months

Population: Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.

AEs are graded using the following criteria using Common Terminology Criteria for Adverse events v5.0: Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL; Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; Grade 5: Death related to AE.

Outcome measures

Outcome measures
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 Participants Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 Participants Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Number of Participants With Severity of Adverse Events Assessed Using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade 1	0 Participants	0 Participants
Number of Participants With Severity of Adverse Events Assessed Using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade 2	5 Participants	2 Participants
Number of Participants With Severity of Adverse Events Assessed Using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade 3	4 Participants	4 Participants
Number of Participants With Severity of Adverse Events Assessed Using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade 4	0 Participants	0 Participants
Number of Participants With Severity of Adverse Events Assessed Using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade 5	0 Participants	0 Participants

Adverse Events

Arm A: Primary Resistance to Initial CPI Therapy

Serious events: 3 serious events

Other events: 9 other events

Deaths: 3 deaths

Arm B: Acquired Resistance to Initial CPI Therapy

Serious events: 2 serious events

Other events: 6 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Arm A: Primary Resistance to Initial CPI Therapy n=9 participants at risk Participants with advanced or metastatic melanoma where primary resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.	Arm B: Acquired Resistance to Initial CPI Therapy n=6 participants at risk Participants with advanced or metastatic melanoma had acquired resistance to initial CPI therapy received a dose of 80 mg (4 tablets of 20 mg) selinexor orally QW and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle (each cycle = 42 days) until PD, intolerable toxicity or withdrawal from the study, whichever occurred first.
Blood and lymphatic system disorders Splenic vein thrombosis	0.00% 0/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	16.7% 1/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Endocrine disorders Adrenal insufficiency	11.1% 1/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	0.00% 0/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	11.1% 1/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	0.00% 0/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Infections and infestations Pneumonia	11.1% 1/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	16.7% 1/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Infections and infestations Sepsis	11.1% 1/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	0.00% 0/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Injury, poisoning and procedural complications Fall	11.1% 1/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	0.00% 0/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Injury, poisoning and procedural complications Subdural haematoma	11.1% 1/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	0.00% 0/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Injury, poisoning and procedural complications Wound complication	11.1% 1/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	0.00% 0/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Renal and urinary disorders Acute kidney injury	0.00% 0/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	16.7% 1/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Respiratory, thoracic and mediastinal disorders Pulmonary cavitation	11.1% 1/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	0.00% 0/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	11.1% 1/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	0.00% 0/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.
Vascular disorders Deep vein thrombosis	0.00% 0/9 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.	16.7% 1/6 • From start of the study treatment up to 24 months Safety population consisted of all enrolled participants who had received at least one dose of both study treatments.

Other adverse events

Additional Information

Karyopharm Medical Information

Karyopharm Therapeutics Inc

Phone: (888) 209-9326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER