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

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ClinicalTrials.gov Identifier: NCT04768881
Recruitment Status : Recruiting
First Posted : February 24, 2021
Last Update Posted : September 13, 2021
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Locally Advanced Unresectable or Metastatic Melanoma Drug: Selinexor Drug: Pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label Multicenter Study to Evaluate the Safety and Efficacy of Selinexor in Combination With Pembrolizumab in Recurrent Advanced Melanoma
Actual Study Start Date : May 12, 2021
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : November 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Arm A: Primary resistance to Initial CPI Therapy
Participants will receive a dose of 80 milligrams (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 until progressive disease (PD), intolerable toxicity or withdrawal from the study, whichever occurs first.
Drug: Selinexor
Dose and formulation: 80 mg (4 tablets of 20 mg)
Other Names:
  • KPT-330
  • XPOVIO™

Drug: Pembrolizumab
Dose and formulation: 400 mg (25 milligrams per milliliter [mg/mL]) Solution
Other Name: Keytruda™

Experimental: Arm B: Acquired Resistance to Initial CPI Therapy
Participants will receive a dose of 80 mg selinexor orally once weekly (QW) and a dose of pembrolizumab 400 mg IV Q6W, both on Day 1 of a 6-week cycle until PD, intolerable toxicity or withdrawal from the study, whichever occurs first.
Drug: Selinexor
Dose and formulation: 80 mg (4 tablets of 20 mg)
Other Names:
  • KPT-330
  • XPOVIO™

Drug: Pembrolizumab
Dose and formulation: 400 mg (25 milligrams per milliliter [mg/mL]) Solution
Other Name: Keytruda™




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 24 months ]

Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Up to 24 months ]
  2. Overall Survival (OS) [ Time Frame: Up to 24 months ]
  3. Complete Response Rate (CRR) [ Time Frame: Up to 24 months ]
  4. Duration of Response (DOR) [ Time Frame: Up to 24 months ]
  5. Disease Control Rate (DCR) [ Time Frame: Up to 24 months ]
  6. Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: Baseline up to 30 Days after End of Treatment (EoT) (EoT: Less than or equal to [≤28] days post-treatment discontinuation) ]
  7. Number of Participants with Clinically Significant Safety Observations: Clinical Laboratory (Hematology and Chemistry), Vital Signs and Physical Examination [ Time Frame: Baseline up to 30 Days after EoT (EoT: ≤28 days post-treatment discontinuation) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

    1. Participants must have confirmed PD per Response Evaluation Criteria in Solid Tumors (RECIST) on or within 12 weeks of the last dose of anti-PD-1/L1 monotherapy or combination therapy (including relatlimab or other anti-LAG-3 mAb) per Society for Immunotherapy in Cancer Guidelines (Kluger,2020).
    2. Arm A (primary resistance): participant has disease progression after receiving at least 6 weeks of prior anti-PD-1/L1 mAb with the best response as PD, or stable disease (SD) less than (<) 6 month (participants with a partial response [PR] or complete response [CR] who have disease progression within 6 months will be considered to have primary resistance in this study).
    3. Arm B (secondary/acquired resistance): participant has disease progression after receiving at least 6 months of prior anti-PD-1/L1 mAb with the best response as CR, PR, or SD greater than (>) 6 months (participants who have disease progression after neoadjuvant or adjuvant therapy, will be considered to have secondary resistance in this study).
    4. Participants who progress on or within 12 weeks after elective discontinuation of anti-PD-1/L1 mono or combination treatment in the absence of PD or treatment limiting toxicity must have confirmed PD per RECIST.
  • 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:

    1. Absolute neutrophil count (ANC) ≥1.5 * 10^9 per liter (L).
    2. Hemoglobin ≥10 gram per deciliter (gm/dL) (≥6.2 millimoles per liter [mmol/L]).
    3. Platelet count ≥100 * 10^9/L.
  • 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:

    1. Not recovered from major surgery ≤28 days prior to Day 1 dosing. Minor procedures, such as biopsies, dental work, or placement of a port or intravenous (IV) line for infusion are permitted.
    2. Have ongoing clinically significant anti-cancer therapy-related toxicities Common Terminology Criteria for Adverse Events (CTCAE) Grade >1. In specific cases, participants whose toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed following documented approval by the Sponsor's Medical Monitor
    3. Had last dose of previous anti-cancer therapy ≤14 days prior to Day 1 dosing
    4. Palliative radiotherapy >14 days prior to the study is allowed
    5. Received investigational drugs in other clinical trials within 28 days, or 5 half-lives of the investigational drug (whichever is shorter), prior to Cycle 1 Day 1 (C1D1).
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04768881


Contacts
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Contact: Jatin Shah, Chief Medical Officer, MD (617) 658-0600 jshah@karyopharm.com
Contact: Sharon Shacham, Chief Scientific Officer, PhD (617) 658-0600 sshacham@karyopharm.com

Locations
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United States, California
The Oncology Institute of Hope and Innovation Recruiting
Pasadena, California, United States, 91105
Contact: Kirsten Bettino       kbettino@airesearch.us   
Principal Investigator: Amitabha Mazumder, MD         
United States, Minnesota
Minnesota Oncology Hematology Recruiting
Minneapolis, Minnesota, United States, 55404
Contact: Lynn Anderson       lynn.anderson@usoncology.com   
Principal Investigator: Timothy Larson, MD         
United States, Nebraska
Great Plains Health Recruiting
North Platte, Nebraska, United States, 69101
Contact: Lisa Kosmacek, RN       kosmacekl@gphealth.org   
Principal Investigator: Kartik Anand, MD         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Edwin Zambrano-Acosta       ez148@rutgers.edu   
Principal Investigator: Adam Berger, MD         
United States, New York
New York Oncology Hematology Recruiting
Albany, New York, United States, 12206
Contact: Amy Zuchelkowski       Amy.Zuchelkowski@usoncology.com   
Principal Investigator: Stephen Wrzesinski, MD         
United States, Ohio
OH Care Clinical Trials Recruiting
Cincinnati, Ohio, United States, 45242
Contact: Eric Clayton       Eric.Clayton@usoncology.com   
Principal Investigator: Suzanne Partridge, MD         
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44144
Contact: Lucy McCahon       mccahol@ccf.org   
Principal Investigator: Brian Gastman, MD         
United States, Texas
Texas Oncology-Austin Central Recruiting
Austin, Texas, United States, 78731
Contact: Francisca Fernandez       Francisca.Fernandez@usoncology.com   
Principal Investigator: Jeffrey Yorio, MD         
Sponsors and Collaborators
Karyopharm Therapeutics Inc
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Responsible Party: Karyopharm Therapeutics Inc
ClinicalTrials.gov Identifier: NCT04768881    
Other Study ID Numbers: XPORT-MEL-033
First Posted: February 24, 2021    Key Record Dates
Last Update Posted: September 13, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Karyopharm Therapeutics Inc:
Karyopharm
Locally advanced unresectable or metastatic melanoma
KPT-330
Recurrent advanced melanoma
Selinexor
Pembrolizumab
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents