Safety and Efficacy of Selinexor in Combination With Pembrolizumab in Recurrent Advanced Melanoma
- Conditions
- Locally Advanced Unresectable or Metastatic Melanoma
- Registration Number
- NCT04768881
- Lead Sponsor
- Karyopharm Therapeutics Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Terminated
- Sex
- All
- Target Recruitment
- 15
Inclusion Criteria:<br><br> - Age greater than or equal to (=) 18 years at the time of informed consent.<br><br> - Participant must have a histologically confirmed diagnosis of locally advanced<br> unresectable stage III or metastatic stage IV melanoma not amenable to local<br> therapy.<br><br> 1. Participants must have confirmed PD per Response Evaluation Criteria in Solid<br> Tumors (RECIST) on or within 12 weeks of the last dose of anti-PD-1/L1<br> monotherapy or combination therapy (including relatlimab or other anti-LAG-3<br> mAb) per Society for Immunotherapy in Cancer Guidelines (Kluger,2020).<br><br> 2. Arm A (primary resistance): participant has disease progression after receiving<br> at least 6 weeks of prior anti-PD-1/L1 mAb with the best response as PD, or<br> stable disease (SD) less than (<) 6 month (participants with a partial response<br> [PR] or complete response [CR] who have disease progression within 6 months<br> will be considered to have primary resistance in this study).<br><br> 3. Arm B (secondary/acquired resistance): participant has disease progression<br> after receiving at least 6 months of prior anti-PD-1/L1 mAb with the best<br> response as CR, PR, or SD greater than (>) 6 months (participants who have<br> disease progression after neoadjuvant or adjuvant therapy, will be considered<br> to have secondary resistance in this study).<br><br> 4. Participants who progress on or within 12 weeks after elective discontinuation<br> of anti-PD-1/L1 mono or combination treatment in the absence of PD or treatment<br> limiting toxicity must have confirmed PD per RECIST.<br><br> - Participants should have at least 1 prior line of CPI therapy but no more than 2.<br><br> - Measurable disease according to RECIST v1.1.<br><br> - Participants with stable previously treated brain metastases are permitted in this<br> study.<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to<br> (=) 1.<br><br> - Adequate bone marrow function at screening, defined as:<br><br> 1. Absolute neutrophil count (ANC) =1.5 * 10^9 per liter (L).<br><br> 2. Hemoglobin =10 gram per deciliter (gm/dL) (=6.2 millimoles per liter [mmol/L]).<br><br> 3. Platelet count =100 * 10^9/L.<br><br> - Serum direct bilirubin =1.5 * upper limit of normal (ULN); aspartate transaminase<br> (AST) and alanine transaminase (ALT) =2.5 * ULN (with confirmed liver metastases:<br> AST and ALT =5 * ULN).<br><br> - Calculated creatinine clearance (CrCl) =15 milliliters per minute (mL/min) based on<br> the Cockcroft and Gault formula.<br><br> - Female participants of childbearing potential must have a negative serum pregnancy<br> test at screening and agree to use highly effective methods of contraception<br> throughout the study and for at least four months following the last dose of study<br> treatment. Childbearing potential excludes: Age >50 years and naturally amenorrhoeic<br> for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy.<br><br> - Male participants who are sexually active must use highly effective methods of<br> contraception throughout the study and for at least four months following the last<br> dose of study treatment. Male participants must agree not to donate sperm during the<br> study treatment period.<br><br> - Written informed consent signed in accordance with federal, local, and institutional<br> guidelines.<br><br>Exclusion Criteria:<br><br> - Metastatic uveal or ocular melanoma.<br><br> - Active central nervous system (CNS) metastases or other CNS (e.g., meningeal)<br> involvement.<br><br> - Participants must have resolution or improvement of immune-mediated treatment<br> related adverse reactions related to prior treatment(s) to Grade =1 without steroid<br> maintenance therapy or his or her previous baseline prior to the corresponding CPI<br> therapy<br><br> a. History of immune-mediated treatment related adverse reactions leading to<br> discontinuation of prior anti-programmed death protein 1 (PD-1), anti-programmed<br> death protein ligand 1 (PD-L1), or anti programmed death protein ligand 2 (PD-L2)<br> monoclonal antibodies (mAbs) or severe hypersensitivity reaction to any mAb or any<br> excipients which in the opinion of the Investigator precludes future use of<br> anti-PD-1/PDL1 therapy.<br><br> - Concurrent systemic steroid therapy higher than physiologic dose (>10 milligrams per<br> day [mg/day] of prednisone or equivalent).<br><br> - Previous treatment with selinexor or other exportin 1 (XPO1) inhibitors.<br><br> - Insufficient time since or not recovered from procedures or anti-cancer therapy,<br> defined as:<br><br> 1. Not recovered from major surgery =28 days prior to Day 1 dosing. Minor<br> procedures, such as biopsies, dental work, or placement of a port or<br> intravenous (IV) line for infusion are permitted.<br><br> 2. Have ongoing clinically significant anti-cancer therapy-related toxicities<br> Common Terminology Criteria for Adverse Events (CTCAE) Grade >1. In specific<br> cases, participants whose toxicity has stabilized or with Grade 2<br> non-hematologic toxicities can be allowed following documented approval by the<br> Sponsor's Medical Monitor<br><br> 3. Had last dose of previous anti-cancer therapy =14 days prior to Day 1 dosing<br><br> 4. Palliative radiotherapy >14 days prior to the study is allowed<br><br> 5. Received investigational drugs in other clinical trials within 28 days, or 5<br> half-lives of the investigational drug (whichever is shorter), prior to Cycle 1<br> Day 1 (C1D1).<br><br> - Live-attenuated vaccine (e.g., nasal spray influenza vaccine) =14 days prior to the<br> intended C1D1.<br><br> - Impairment of gastrointestinal (GI) function or GI disease that could significantly<br> alter the absorption of selinexor (e.g., vomiting, or diarrhea that is CTCAE version<br> 5.0 grade >1).<br><br> - Life expectancy less than (<) 4 months based on the opinion of the Investigator<br><br> - Active pneumonitis requiring steroid therapy.<br><br> - Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics,<br> antivirals, or antifungals within 7 days prior to first dose of study treatment;<br> however, prophylactic use of these agents is acceptable (including parenteral).<br><br> - Any life-threatening illness, medical condition, or organ system dysfunction which,<br> in the Investigator's opinion, could compromise the participant's safety, prevent<br> the participant from giving informed consent, or being compliant with the study<br> procedures.<br><br> - Female participants who are pregnant or lactating.<br><br> - Active hepatitis B virus treated with antiviral therapy for hepatitis B within 8<br> weeks with a viral load >100 international units per milliliter (IU/mL).<br><br> - Untreated hepatitis C virus positive without documentation of negative viral load<br> per institutional standard.<br><br> - Human immunodeficiency virus positive with CD4+T-cells =350 cells per microliter,<br> positive viral load per institutional standard, and a history of acquired<br> immunodeficiency syndrome defining opportunist infections in the last year.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Assessed as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) as Per RECIST v 1.1;Overall Survival (OS);Complete Response Rate (CRR);Duration of Response (DOR) as Per RECIST v 1.1;Percentage of Participants With Disease Control Rate (DCR) as Per RECIST v 1.1;Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs;Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters;Number of Participants With Clinically Significant Changes in Vital Signs;Number of Participants With Clinically Significant Changes in Physical Examination;Number of Participants With Severity of Adverse Events Assessed Using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0