Study Comparing Pembrolizumab With Dual MAPK Pathway Inhibition Plus Pembrolizumab in Melanoma Patients
NCT ID: NCT02625337
Last Updated: 2017-09-15
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE2
32 participants
INTERVENTIONAL
2016-01-31
2018-12-31
Brief Summary
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Stratification will be baseline LDH level and baseline PD-L1 expression.
Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Pembrolizumab mono
Pembrolizumab monotherapy
Pembrolizumab
Biopsy
Biopsies will be taken during screening, before randomization, at week 8 (only arm 2-4) after 12 weeks, at week 18 and if PD.
Blood taking
Blood will be taken for PBMCs during screening (twice), before randomization, at weeks 12 at week 18 and if PD.
Pembrolizumab with dabrafenib+trametinib short
Pembrolizumab combined with a short scheme of dabrafenib+trametinib
Pembrolizumab
Dabrafenib
Trametinib
Biopsy
Biopsies will be taken during screening, before randomization, at week 8 (only arm 2-4) after 12 weeks, at week 18 and if PD.
Blood taking
Blood will be taken for PBMCs during screening (twice), before randomization, at weeks 12 at week 18 and if PD.
Pembrolizumab with dabrafenib+trametinib intermediate
Pembrolizumab combined with an intermediate scheme of dabrafenib+trametinib
Pembrolizumab
Dabrafenib
Trametinib
Biopsy
Biopsies will be taken during screening, before randomization, at week 8 (only arm 2-4) after 12 weeks, at week 18 and if PD.
Blood taking
Blood will be taken for PBMCs during screening (twice), before randomization, at weeks 12 at week 18 and if PD.
Pembrolizumab with dabrafenib+trametinib long
Pembrolizumab combined with a long scheme of dabrafenib+trametinib
Pembrolizumab
Dabrafenib
Trametinib
Biopsy
Biopsies will be taken during screening, before randomization, at week 8 (only arm 2-4) after 12 weeks, at week 18 and if PD.
Blood taking
Blood will be taken for PBMCs during screening (twice), before randomization, at weeks 12 at week 18 and if PD.
Interventions
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Pembrolizumab
Dabrafenib
Trametinib
Biopsy
Biopsies will be taken during screening, before randomization, at week 8 (only arm 2-4) after 12 weeks, at week 18 and if PD.
Blood taking
Blood will be taken for PBMCs during screening (twice), before randomization, at weeks 12 at week 18 and if PD.
Eligibility Criteria
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Inclusion Criteria
* World Health Organization (WHO) Performance Status 0-2
* Histologically/cytologically confirmed stage IV BRAF V600E or K metastatic melanoma
* Measurable disease according to RECIST 1.1
* At least one easy accessible lesion (s.c., lymph node) that can be repeatedly biopsied
* Patient willing to undergo triple tumor biopsies during screening, at week 6, week 8 (cohorts 2-4 only), week 12, at week 18, and in case of disease progression.
* No prior immunotherapy targeting PD-1 or PD-L1 (CTLA-4 targeting therapy is allowed)
* No prior BRAF and/or MEK targeting therapy
* No immunosuppressive medications
* Screening laboratory values must meet the following criteria:
WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 5.0 mmol/L Creatinine ≤ 2x ULN AST, ALT ≤ 2.5 x ULN (≤5 x ULN for patients with liver metastases) Bilirubin ≤2 X ULN
* Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Women of child bearing potential must agree to use a reliable form of contraceptive during the study treatment period and for at least 120 days following the last dose of study drug
* Men must agree to the use of male contraception during the study Treatment Period and for at least 180 days after the last dose of study drug.
Exclusion Criteria
* Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
* Presence of symptomatic brain or leptomeningeal metastases; patients with asymptomatic brain metastases detected during screening for this study are allowed to participate in this study
* Prior PD-1/PD-L1 targeting immunotherapy
* Has an active automimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
* Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
* Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
* Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
* Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
* Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
* Known history of Human Immunodeficiency Virus;
* Active infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA);
* Has active tuberculosis
* Has received a live vaccine within 30 days prior to the first dose of trial treatment.
* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Patients that have had another malignancy, but are free of tumor for more than 2 years are allowed for inclusion.
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
The Netherlands Cancer Institute
OTHER
Responsible Party
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Principal Investigators
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Christian U. Blank, Prof.
Role: PRINCIPAL_INVESTIGATOR
Medical oncologist/researcher
Locations
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Antoni van Leeuwenhoek ziekenhuis
Amsterdam, North Holland, Netherlands
Countries
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Central Contacts
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Facility Contacts
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References
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Rozeman EA, Versluis JM, Sikorska K, Hoefsmit EP, Dimitriadis P, Rao D, Lacroix R, Grijpink-Ongering LG, Lopez-Yurda M, Heeres BC, van de Wiel BA, Flohil C, Sari A, Heijmink SWTPJ, van den Broek D, Broeks A, de Groot JWB, Vollebergh MA, Wilgenhof S, van Thienen JV, Haanen JBAG, Blank CU. IMPemBra: a phase 2 study comparing pembrolizumab with intermittent/short-term dual MAPK pathway inhibition plus pembrolizumab in patients with melanoma harboring the BRAFV600 mutation. J Immunother Cancer. 2023 Jul;11(7):e006821. doi: 10.1136/jitc-2023-006821.
Other Identifiers
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N15IMP
Identifier Type: -
Identifier Source: org_study_id