Melanoma Stage IIIEarly Phase 1NCT04741997
Adjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib Binimetinib in Melanoma
A Early Phase 1 study testing Encorafenib Pill, Binimetinib Pill and Nivolumab in people with Melanoma Stage III and Melanoma Stage IV, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to assess rate of disease relapse and hazard rate of disease relapse after neoadjuvant therapy based on the statuses of pathologic complete response or non-pathologic complete response, and postoperative adjuvant therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage III, Melanoma Stage IV, BRAF V600 Mutation
- What is being tested?
- Encorafenib Pill, Binimetinib Pill and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 24 May 2021to Apr 2027
- Phase
- Early Phase 1
- 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
- Age ≥ 18 years at the time of informed consent
- Histologically confirmed diagnosis of melanoma. Any primary or unknown origin is permitted.
- Melanoma must have a BRAFV600 mutation (using a CLIA-validated assay), either stage III (B/C/D) or Stage IV (AJCC 8th edition).
- ECOG performance status ≤ 2
- Adequate laboratory parameters as well:
- a. Hemoglobin ≥ 8 g/dL.
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- b. Platelets ≥ 75 × 109/L;
- c. AST and ALT ≤ 2.5 × ULN; in participants with liver metastases ≤ 5 × ULN;
- d. Total bilirubin ≤ 1.5 × ULN and < 2 mg/dL; OR total bilirubin >1.5 × ULN with indirect bilirubin < 1.5 × ULN;
- e. Serum creatinine ≤ 2.0 × ULN
- Female participants of childbearing potential as described in protocol, must have a negative serum or urine β-HCG test result. Female participants of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, as described in Section 4.3.1. Participants must agree to not use hormonal contraceptives, as encorafenib can result in decreased concentration and loss of efficacy. Male participants must agree to use methods of contraception that are highly effective or acceptable per protocol.
Who cannot join
- Participants may have received prior therapy with BRAF and/or a MEK inhibitor if it was completed at least 6 months prior to study enrollment. Patients who had prior disease progression while on BRAF/MEK inhibitor therapy are not eligible. (Progression after stopping treatment is permitted.) Participants may have received prior therapy an anti-PD-1/PD-L1 or CTLA-4 inhibitor.
- Participants must not have had adverse events related to encorafenib and/or binimetinib specifically, that required discontinuation of one or both drugs due to toxicity.
- Participants who have had major surgery or radiotherapy ≤ 14 days prior to start of study treatment or who have not recovered from side effects of such procedure.
- Participants must be willing to avoid consuming grapefruit, pomegranates, star fruits, Seville oranges or products containing the juice during the study while they are taking encorafenib/binimetinib.
- Uncontrolled or symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable, require steroids, are potentially life-threatening or have required radiation within 28 days prior to starting study drug. Patients with previously treated brain metastases may participate provided they are stable (e.g.,without evidence of progression by radiographic imaging for at least 28 days before the first dose of study treatment and neurologic symptoms have returned to baseline).
- Impaired cardiovascular function as below:
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- a. Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 3);
- b. presence of uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia
- c. Baseline QTcF interval ≥ 500 ms.
- Known history of retinal vein occlusion (RVO)
- Current use of a prohibited medication (including herbal medications, supplements, or foods), as described in protocol, or use of a prohibited medication ≤ 1 week prior to the start of study treatment.
- Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to randomization.
- Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load prior to randomization.
- Pregnancy or breast feeding.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Zeynep Eroglu, MD
Andrew Brohl, MD
About this study
Official title: A Randomized Pilot Trial of Adjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib and Binimetinib in Advanced Melanoma
The purpose of this study is to assess rate of disease relapse and hazard rate of disease relapse after neoadjuvant therapy based on the statuses of pathologic complete response or non-pathologic complete response, and postoperative adjuvant therapy.
- Conditions
- Melanoma Stage III, Melanoma Stage IV, BRAF V600 Mutation
- Being tested
- Encorafenib Pill, Binimetinib Pill, Nivolumab
- Keywords
- Skin
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Encorafenib PillDrug
Encorafenib 450 mg will be administered orally once per day in continuous 28-day cycles
Binimetinib PillDrug
Binimetinib 45 mg will be administered orally twice per day in continuous 28-day cycles
NivolumabDrug
Nivolumab will be administered at a dose of 480 mg IV infusion over 30 minutes every 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Surveillance | Active comparator | Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have pathologic complete response they will receive adjuvant treatment for 24 weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery. Receives: Drug: Encorafenib Pill; Drug: Binimetinib Pill |
| Encorafenib and Binimetinib after Pathologic Complete Response | Experimental | Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have pathologic complete response they will continue to receive encorafenib and binimetinib for 24 more weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery. Receives: Drug: Encorafenib Pill; Drug: Binimetinib Pill |
| Encorafenib and Binimetinib after Non-Pathologic Complete Response | Experimental | Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have non-pathologic complete response they will continue to receive encorafenib and binimetinib for 24 more weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery. Receives: Drug: Encorafenib Pill; Drug: Binimetinib Pill |
| Nivolumab after Non-Pathologic Complete Response | Experimental | Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have non-pathologic complete response they will receive nivolumab for 24 weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery. Receives: Drug: Encorafenib Pill; Drug: Binimetinib Pill; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Disease Relapse
Investigators will estimate the rate of disease relapse after neoadjuvant therapy based on pathologic complete response status and postoperative adjuvant therapy within each arm.
Measured: After surgery up to 24 weeks
Secondary outcomes (5)
Relapse Free Survival
Relapse free survival is defined as time from surgery until disease relapse
Measured: After surgery up to 24 weeks
Rate of Pathologic Complete Response
Investigators will measure the rate of pathologic complete response after surgery.
Measured: At 26 weeks
Rate of Non-Pathologic Complete Response
Investigators will measure the rate of non-pathologic complete response after surgery.
Measured: At 26 weeks
Overall Response Rate
Overall response rate will be measured after neoadjuvant therapy (for participants who have measurable disease per RECIST 1.1 at start of neoadjuvant therapy).
Measured: Up to 26 weeks
Overall Survival
Overall survival will be measured from time of surgery to death from any cause.
Measured: After surgery, up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2021
- Study start24 May 2021
- Primary completionApr 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Stage IIIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Zeynep Eroglu, MD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04741997
- Sponsor's protocol ID
- MCC-20641
- Status last verified
- Sep 2026
- First submitted
- 2 Feb 2021
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Pilot Trial of Adjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib and Binimetinib in Advanced Melanoma
- ClinicalTrials.gov ID
- NCT04741997
- Acronym / sponsor ID
- MCC-20641
- Conditions
- Melanoma Stage III, Melanoma Stage IV, BRAF V600 Mutation
- Keywords
- Skin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 24 May 2021 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 5 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess rate of disease relapse and hazard rate of disease relapse after neoadjuvant therapy based on the statuses of pathologic complete response or non-pathologic complete response, and postoperative adjuvant therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Surveillance | Active comparator | Drug: Encorafenib Pill, Drug: Binimetinib PillParticipants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have pathologic complete response they will receive adjuvant treatment for 24 weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery. |
| Encorafenib and Binimetinib after Pathologic Complete Response | Experimental | Drug: Encorafenib Pill, Drug: Binimetinib PillParticipants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have pathologic complete response they will continue to receive encorafenib and binimetinib for 24 more weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery. |
| Encorafenib and Binimetinib after Non-Pathologic Complete Response | Experimental | Drug: Encorafenib Pill, Drug: Binimetinib PillParticipants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have non-pathologic complete response they will continue to receive encorafenib and binimetinib for 24 more weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery. |
| Nivolumab after Non-Pathologic Complete Response | Experimental | Drug: Encorafenib Pill, Drug: Binimetinib Pill, Drug: NivolumabParticipants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have non-pathologic complete response they will receive nivolumab for 24 weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years at the time of informed consent
- Histologically confirmed diagnosis of melanoma. Any primary or unknown origin is permitted.
- Melanoma must have a BRAFV600 mutation (using a CLIA-validated assay), either stage III (B/C/D) or Stage IV (AJCC 8th edition).
- ECOG performance status ≤ 2
- Adequate laboratory parameters as well:
Key exclusion criteria (15 listed)
- Participants may have received prior therapy with BRAF and/or a MEK inhibitor if it was completed at least 6 months prior to study enrollment. Patients who had prior disease progression while on BRAF/MEK inhibitor therapy are not eligible. (Progression after stopping treatment is permitted.) Participants may have received prior therapy an anti-PD-1/PD-L1 or CTLA-4 inhibitor.
- Participants must not have had adverse events related to encorafenib and/or binimetinib specifically, that required discontinuation of one or both drugs due to toxicity.
- Participants who have had major surgery or radiotherapy ≤ 14 days prior to start of study treatment or who have not recovered from side effects of such procedure.
- Participants must be willing to avoid consuming grapefruit, pomegranates, star fruits, Seville oranges or products containing the juice during the study while they are taking encorafenib/binimetinib.
- Uncontrolled or symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable, require steroids, are potentially life-threatening or have required radiation within 28 days prior to starting study drug. Patients with previously treated brain metastases may participate provided they are stable (e.g.,without evidence of progression by radiographic imaging for at least 28 days before the first dose of study treatment and neurologic symptoms have returned to baseline).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Encorafenib PillEncorafenib 450 mg will be administered orally once per day in continuous 28-day cycles | Drug | Encorafenib and Binimetinib after Non-Pathologic Complete Response, Encorafenib and Binimetinib after Pathologic Complete Response, Nivolumab after Non-Pathologic Complete Response, Surveillance |
| Binimetinib PillBinimetinib 45 mg will be administered orally twice per day in continuous 28-day cycles | Drug | Encorafenib and Binimetinib after Non-Pathologic Complete Response, Encorafenib and Binimetinib after Pathologic Complete Response, Nivolumab after Non-Pathologic Complete Response, Surveillance |
| NivolumabNivolumab will be administered at a dose of 480 mg IV infusion over 30 minutes every 4 weeks. | Drug | Nivolumab after Non-Pathologic Complete Response |
Primary outcome
Rate of Disease Relapse
Time frame: After surgery up to 24 weeks
Investigators will estimate the rate of disease relapse after neoadjuvant therapy based on pathologic complete response status and postoperative adjuvant therapy within each arm.
5 secondary outcomes
Relapse Free Survival
Time frame: After surgery up to 24 weeks
Rate of Pathologic Complete Response
Time frame: At 26 weeks
Rate of Non-Pathologic Complete Response
Time frame: At 26 weeks
Overall Response Rate
Time frame: Up to 26 weeks
Overall Survival
Time frame: After surgery, up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zeynep Eroglu, MD principal investigator
Moffitt Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Encorafenib Pill, Binimetinib Pill and Nivolumab in people with Melanoma Stage III and Melanoma Stage IV, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
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 11 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 16 Sep 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 States. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Contact Arnay Marshall (813-745-5938, Arnay.Marshall@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Disease Relapse (time frame: After surgery up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Sep 2026.