Status and phase
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Treatments
About
Approximately 40 participants with locally advanced or metastatic melanoma will be enrolled in 20 sites in the United States into 1 of the following 2 arms: Primary resistance to initial checkpoint inhibitor (CPI) therapy in Arm A and Acquired resistance to initial CPI therapy in Arm B. Participants who have disease progression (PD) after discontinuation of CPIs, especially in neoadjuvant or adjuvant therapy, will be considered to have acquired resistance in this study. Participants will receive study treatment (Selinexor and Pembrolizumab) until PD, intolerable toxicity or withdrawal from the study, whichever occurs first.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Age greater than or equal to (≥) 18 years at the time of informed consent.
Participant must have a histologically confirmed diagnosis of locally advanced unresectable stage III or metastatic stage IV melanoma not amenable to local therapy.
Participants should have at least 1 prior line of CPI therapy but no more than 2.
Measurable disease according to RECIST v1.1.
Participants with stable previously treated brain metastases are permitted in this study.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (≤) 1.
Adequate bone marrow function at screening, defined as:
Serum direct bilirubin ≤1.5 * upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 * ULN (with confirmed liver metastases: AST and ALT ≤5 * ULN).
Calculated creatinine clearance (CrCl) ≥15 milliliters per minute (mL/min) based on the Cockcroft and Gault formula.
Female participants of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception throughout the study and for at least four months following the last dose of study treatment. Childbearing potential excludes: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy.
Male participants who are sexually active must use highly effective methods of contraception throughout the study and for at least four months following the last dose of study treatment. Male participants must agree not to donate sperm during the study treatment period.
Written informed consent signed in accordance with federal, local, and institutional guidelines.
Exclusion criteria
Metastatic uveal or ocular melanoma.
Active central nervous system (CNS) metastases or other CNS (e.g., meningeal) involvement.
Participants must have resolution or improvement of immune-mediated treatment related adverse reactions related to prior treatment(s) to Grade ≤1 without steroid maintenance therapy or his or her previous baseline prior to the corresponding CPI therapy
a. History of immune-mediated treatment related adverse reactions leading to discontinuation of prior anti-programmed death protein 1 (PD-1), anti-programmed death protein ligand 1 (PD-L1), or anti programmed death protein ligand 2 (PD-L2) monoclonal antibodies (mAbs) or severe hypersensitivity reaction to any mAb or any excipients which in the opinion of the Investigator precludes future use of anti-PD-1/PDL1 therapy.
Concurrent systemic steroid therapy higher than physiologic dose (>10 milligrams per day [mg/day] of prednisone or equivalent).
Previous treatment with selinexor or other exportin 1 (XPO1) inhibitors.
Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as:
Live-attenuated vaccine (e.g., nasal spray influenza vaccine) ≤14 days prior to the intended C1D1.
Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor (e.g., vomiting, or diarrhea that is CTCAE version 5.0 grade >1).
Life expectancy less than (<) 4 months based on the opinion of the Investigator
Active pneumonitis requiring steroid therapy.
Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participant's safety, prevent the participant from giving informed consent, or being compliant with the study procedures.
Female participants who are pregnant or lactating.
Active hepatitis B virus treated with antiviral therapy for hepatitis B within 8 weeks with a viral load >100 international units per milliliter (IU/mL).
Untreated hepatitis C virus positive without documentation of negative viral load per institutional standard.
Human immunodeficiency virus positive with CD4+T-cells ≤350 cells per microliter, positive viral load per institutional standard, and a history of acquired immunodeficiency syndrome defining opportunist infections in the last year.
Primary purpose
Allocation
Interventional model
Masking
15 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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