Status unknownNCT02625337IMPemBraUpdated Sep 15, 2017

Study Comparing Pembrolizumab With Dual MAPK Pathway Inhibition Plus Pembrolizumab in Melanoma Patients

A Phase 2 interventional study of Pembrolizumab and Dabrafenib in Metastatic Melanoma, sponsored by The Netherlands Cancer Institute. Status unknown at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-09-15.

Sponsored by The Netherlands Cancer Institute · Phase 2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Sep 2017), so the status shown — last known as Recruiting — may be out of date.

Phase: Phase 2
Study type: Interventional
Enrollment: 32
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

This is a Phase 2 trial consisting of 24 patients receiving the combination of dabrafenib + trametinib + pembrolizumab in 3 different dosing schemes and 8 patients receiving pembrolizumab standard monotherapy. All patients start with pembrolizumab standard therapy for 6 weeks and will then be randomized to continue pembrolizumab monotherapy or to receive additional intermitted/short-term dabrafenib + trametinib.

Stratification will be baseline LDH level and baseline PD-L1 expression.

Conditions studied

Metastatic Melanoma

Browse trials for

Melanoma 3,073

In context

Melanoma

3,073 studies on the registry are indexed under Melanoma; 529 are open to participants now.

This study's planned enrollment of 32 is below the median of 38 across 2,400 interventional studies indexed under Melanoma.

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Lead sponsor

The Netherlands Cancer Institute is the lead sponsor of 230 studies on the registry; 66 are open to participants now.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Adults at least 18 years of age
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

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from this study:

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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 32 participants (estimated)

Study arms

Active comparator
Pembrolizumab mono
Pembrolizumab monotherapy
Drug: Pembrolizumab · Procedure: Biopsy · Procedure: Blood taking
Experimental
Pembrolizumab with dabrafenib+trametinib short
Pembrolizumab combined with a short scheme of dabrafenib+trametinib
Drug: Pembrolizumab · Drug: Dabrafenib · Drug: Trametinib · Procedure: Biopsy · Procedure: Blood taking
Experimental
Pembrolizumab with dabrafenib+trametinib intermediate
Pembrolizumab combined with an intermediate scheme of dabrafenib+trametinib
Drug: Pembrolizumab · Drug: Dabrafenib · Drug: Trametinib · Procedure: Biopsy · Procedure: Blood taking
Experimental
Pembrolizumab with dabrafenib+trametinib long
Pembrolizumab combined with a long scheme of dabrafenib+trametinib
Drug: Pembrolizumab · Drug: Dabrafenib · Drug: Trametinib · Procedure: Biopsy · Procedure: Blood taking

Interventions

DrugPembrolizumab
DrugDabrafenib
DrugTrametinib
ProcedureBiopsy
Biopsies will be taken during screening, before randomization, at week 8 (only arm 2-4) after 12 weeks, at week 18 and if PD.
ProcedureBlood taking
Blood will be taken for PBMCs during screening (twice), before randomization, at weeks 12 at week 18 and if PD.

What researchers measure

Primary outcomes

Safety of different schemes of continuous/intermittent dabrafenib+trametinib during treatment with pembrolizumab as compared to pembrolizumab monotherapy as measured by SUSARs.
Safety as measured by SUSARs during treatment week 0 till week 18.
Time frame: 18 weeks from baseline
Feasibility of different schemes of continuous/intermittent dabrafenib+trametinib during treatment with pembrolizumab as compared to pembrolizumab monotherapy as measured by adherence to the timelines in the study protocol.
Feasibility as measured by adherence to the timelines in the study protocol (week 0 till week 18).
Time frame: 18 weeks from baseline.
The immune-activating capacity of different schemes of continuous/intermittent dabrafenib+trametinib during treatment with pembrolizumab as compared to pembrolizumab monotherapy
Readout will be the alterations in magnitude or breadth of the self-antigen specific T cell responses in the time interval pre-treatment to week 18 intrapatient, and interpatient, pembrolizumab only (cohort 1) versus pembrolizumab plus intermittent dabrafenib/ trametinib (cohorts 2-4). To this purpose, we will analyze melanoma antigen-specific T cells responses by HLA-A2-restricted MHC-tetramer staining.
Time frame: 18 weeks from baseline.

Secondary outcomes

To determine rates of response at week 6, 12, week 18.
Rates of response at week 6, week 12, week 18 according to RECIST 1.1 criteria
Time frame: Screening, week 6, 12 and 18
To determine progression-free survival starting from randomization.
Progression-free survival (PFS) starting from randomization to progression using RECIST 1.1 criteria.
Time frame: From randomisation until PD, median 10 months.
Long-term toxicities of intermittent dabrafenib + trametinib during treatment with pembrolizumab as compared to pembrolizumab monotherapy
Rate and type of late adverse events
Time frame: From beyond week 18, up to 2 years follow-up.

Other outcomes

To describe time to progression beginning from week 12 (cohorts 2-4).
As the short addition of dabrafenib+trametinib will induce for short time tumor regressions we will analyze cohorts 2-4 with a second baseline, namely the end of the targeted therapy at week 12, for progression free survival using to RECIST 1.1
Time frame: Randomisation until week 12.
Changes of immune parameters within the tumor.
In addition to the primary readout (broadening of the melanoma-specific T cell response in peripheral blood), we will analyze the effect of the different therapy schemes on tumor immune cell infiltration (IHC for CD3, CD4, CD8, CD68, FoxP3, PD-L1, PD-L2, PD-1, CD11b, HLA).
Time frame: 18 weeks from baseline.

Study locations

1 of 1 sites recruiting

Antoni van Leeuwenhoek ziekenhuis
Amsterdam, North Holland 1066CX, Netherlands
- Christian U. Blank, Prof. · Contact · c.blank@nki.nl
Recruiting

References and documents

Publications

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. PubMed 37479483 ↗

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Jan 2016, a primary completion of Jun 2018 and a completion of Dec 2018. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered: Dec 1, 2015
First posted: Dec 9, 2015
Start: Jan 2016
Primary completionEst.: Jun 2018
CompletionEst.: Dec 2018
Last update: Sep 15, 2017

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Sep 15, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02625337
Lead sponsor: The Netherlands Cancer Institute
Collaborators: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Dec 9, 2015
Start date: Jan 2016
Primary completion: Jun 2018 (estimated)
Completion: Dec 2018 (estimated)
Last update: Sep 15, 2017

Study contacts

Christian U. Blank, Prof.

Contact

c.blank@nki.nl

+31205122570

Christian U. Blank, Prof.

principal investigator · Medical oncologist/researcher

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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This study is status unknown, as verified in Sep 2017. You cannot join it, but the record below documents what was studied.

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