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MelanomaPhase 2PREMIUMNCT05097378

Perioperative Encobini in BRAFV600 Mutant Stage III (B/C/D) or Oligometastatic Stage IV Melanoma

A Phase 2 study testing Encorafenib + Binimetinib and Standard Adjuvant Treatment in people with Melanoma and Cancer, run by CCTU- Cancer Theme at 1 site in United Kingdom.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

A two-arm, randomised trial investigating the response of encorafenib and binimetinib compared to standard adjuvant therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma, Cancer
What is being tested?
Encorafenib + Binimetinib and Standard Adjuvant Treatment
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited Kingdom
Study dates
27 Feb 2023to 31 May 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent to participate
  • Aged ≥ 18 years old
  • AJCC 8th edition stage III (B/C/D), or extracranial oligometastatic stage IV BRAFV600 mutant melanoma, based on histological/cytological and radiological assessments for which surgery is planned, and resection is expected to remove all known tumour(s) with R0 resection margins. 'Oligometastatic stage IV' is defined for the purpose of this trial as M stage disease confined to a single body organ excluding the brain that can be readily removed surgically with anticipated clear margins
  • For stage III patients, confirmation of no evidence of distant metastatic disease using preferred imaging modalities including CT body or PET/CT and CT or MRI head
  • For stage IV patients, confirmation of no evidence of unresectable metastatic disease, or metastatic disease in more than 1 body organ, using preferred imaging modalities including CT body or PET/CT and CT or MRI head. The site of metastasis should not be in bone, or CNS, or in any other body site where complete resection is not feasible
  • The planned resectable disease must be radiologically measurable using standard imaging modalities.
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  • Baseline tumour assessments must be done within 28 days prior to randomisation
  • BRAF V600 mutation confirmation
  • Received no prior BRAF or MEK inhibitors
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Predicted life expectancy >12 months
  • Normal QTc interval (<480msec) on ECG and left ventricular ejection fraction within normal limits, assessed by echocardiogram or MUGA
  • Adequate bone marrow function defined as:
  • Absolute neutrophil count (ANC) ≥1.5 x 109 /L
  • Haemoglobin (Hb) ≥ 90 g/L
  • Platelets ≥100 x 109 /L
  • Adequate liver function defined as:
  • Aspartate aminotransferase (AST) and/or alanine transaminase (ALT) ≤2.5 x upper limit of normal range (ULN)
  • Total bilirubin <1.5 x ULN (except if the patient has Gilbert Syndrome or liver metastases, in which case the bilirubin must be <3 x ULN)
  • Adequate renal function defined as:
  • a serum creatinine ≤1.5 x ULN or
  • calculated creatinine clearance by Cockcroft-Gault of ≥40 mL/min
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, completion of QoL and PROM questionnaires and other procedures described in the protocol
  • Women of child-bearing potential (WCBP) and all sexually active male patients must agree to use effective contraception methods throughout treatment
  • Be able to swallow the trial medication
  • Confirmation of adequate diagnostic tumour tissue available for research studies

Who cannot join

  • Prior adjuvant therapy for resected primary or loco-regional melanoma
  • Other invasive malignancies diagnosed within the last 2 years which are not in complete remission, or for which additional therapy is required
  • Brain or bone metastases
  • Non-cutaneous primary site of melanoma
  • History or current evidence of retinal vein occlusion (RVO) or risk factors for RVO (uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes)
  • Left ventricular function <50%
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  • Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to:
  • Patients with uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction (MI), new angina, stroke transient ischaemic attack (TIA), or new congestive cardiac failure (CCF)) within the last 6 months
  • Uncontrolled hypertension
  • Patients with stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification (NYHF) III or IV or frequent angina
  • Patients with baseline QTC interval > 480 msec on electrocardiogram (ECG)
  • Left ventricular ejection fraction below the lower limit of normal
  • Presence of active infection
  • Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C
  • Known allergy or hypersensitivity to Encorafenib or Binimetinib, or their excipients. Binimetinib contains lactose, so patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption will be excluded.
  • Women who are pregnant, plan to become pregnant or are lactating during the trial period
  • Use of any other investigational anti-cancer drugs (a washout period of 28 days would be required)
  • Use of strong inducers and inhibitors of CYP3A4 (Appendix 4 - Prohibited Medication)
  • Known HIV or active Hep B or Hep C infection
  • Patients who have neuromuscular disorders associated with elevated creatine phosphokinase (CK, e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
  • Autoimmune conditions requiring regular or intermittent use of any systemic steroid or immunosuppressive drugs, with the exception of steroid inhalers
  • Any immunotherapy in the last 3 months
  • Prior radiotherapy to the site of disease planned for resection
  • Concurrent participation in an interventional clinical trial (observational studies allowed)

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Addenbrooke's Hospital

    Cambridge, England, CB2 2QQ

Other trials in United Kingdom

About this study

Official title: Perioperative Encorafinib+Binimetinib in BRAFV600 Mutant Clinically Detected AJCC Stage III (B/C/D) or Oligometastatic Stage IV Melanoma

A two-arm, randomised trial investigating the response of encorafenib and binimetinib compared to standard adjuvant therapy.

Read the detailed description

A phase II, multi-centre, open label, randomised trial.

The trial will assess the delivery, response rate, treatment compliance, efficacy and safety of encorafenib and binimetinib compared to standard adjuvant therapy in patients with BRAFV600 mutant clinically detected AJCC stage III(B/C/D) or oligometastatic stage IV Melanoma.

Conditions
Melanoma, Cancer
Being tested
Encorafenib + Binimetinib, Standard Adjuvant Treatment
Medical subject headings
Melanoma, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Encorafenib + BinimetinibDrug

    Also called Braftovi + Mektovi

    Encorafenib is a potent and highly selective ATP-competitive small molecule RAF kinase inhibitor, which suppresses the RAF/MEK/ERK pathway in tumour cells expressing several mutated forms of BRAF kinase (V600E, D and K).

    Binimetinib is an ATP-uncompetitive, reversible inhibitor of the kinase activity of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2. Binimetinib inhibits activation of MEK by BRAF and inhibits MEK kinase activity

  • Standard Adjuvant TreatmentDrug

    Standard Adjuvant Treatment

Study groups in NCT05097378
Study groupRoleWhat they receive
EncoBini ArmExperimentalOral encorafenib 450mg once daily and oral binimetinib 45mg twice daily for 8 weeks pre-operative and for up to 44 weeks post-operative.
Receives: Drug: Encorafenib + Binimetinib
Standard ArmActive comparatorImmediate surgery followed by Investigator's choice of standard adjuvant therapy to commence within 12 weeks of surgery and to continue for up to 52 weeks.
Receives: Drug: Standard Adjuvant Treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological response rate

    % of patients with a complete response using Haemotoxylin and Eosin staining of tumour removed at surgery.

    Measured: During scheduled surgery

Secondary outcomes (7)

  1. Treatment compliance

    Incidence of missed treatment doses assessed from number of tablets returned.

    Measured: Through study completion for an average of 12 months

  2. Radiological response

    % of patients with a complete response using CT scan tumour measurement assessment (RECIST) from start of treatment until 8 weeks.

    Measured: Through study completion for an average of 12 months

  3. Toxicity of treatment

    Rate of patients with drug related toxicities reported from start of study until end of treatment

    Measured: Through study completion for an average of 12 months

  4. Lymphoedema toxicity

    Incidence of lymphoedema toxicity using circumferential limb measurement and questionnaires for an average of 12 months.

    Measured: Through study completion for an average of 12 months

  5. Survival rate

    Number of patients deceased from start of treatment for an average of 12 months.

    Measured: Through study completion for an average of 12 months

  6. Quality of life

    Overall quality of life quality of life to be measured and assessed by Functional Assessment of Cancer Therapy - Melanoma (FACT-M) questionnaire for an average of 12 months.

    Measured: Through study completion for an average of 12 months

  7. Recruitment rate

    Rate of monthly recruitment achieved during the last 6 months of the trial recruitment period

    Measured: Through study completion for an average of 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2021
  2. Study start27 Feb 2023
  3. Primary completion23 Jan 2026
  4. Study completion31 May 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Neoadjuvant and adjuvant administration schedule
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05097378
Sponsor's protocol ID
PREMIUM
Other IDs
2019-004855-35, 2019
Acronym
PREMIUM
Status last verified
Oct 2026
First submitted
4 Oct 2021
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Encorafenib + Binimetinib and Standard Adjuvant Treatment in people with Melanoma and Cancer, run by CCTU- Cancer Theme at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological response rate (time frame: During scheduled surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05097378.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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