18 and older, any sex, with Metastatic Melanoma or Brain Metastases. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Intracranial Objective Response (iORR) by Modified RECIST 1.1 Before Local Radiotherapy Treatment in Full DatasetPrimary· 24 months after start of treatment
iORR calculated as the proportion of patient with a best overall intracranial response of complete response (CR) or partial response (PR) before local treatment according to modified RECIST 1.1.
Modified RECIST 1.1 consists of:
Up to 5 intracranial lesions could be selected as target lesions Target lesions might have a longest diameter ≥ 5 mm when evaluated by contrast-enhanced MRI
This endpoint was also independently reported in patients with symptomatic and asymptomatic brain metastasis.
Full analysis set
Group
Value
95% CI
COMBO450
34
COMBO450
13
COMBO450
1
Asymptomatic brain metastasis
Group
Value
95% CI
COMBO450
20
COMBO450
5
COMBO450
0
Symptomatic brain metastasis
Group
Value
95% CI
COMBO450
14
COMBO450
8
COMBO450
1
Duration of Intracranial ResponseSecondary· Throughout the study period, up to approximately 24 months
Calculated as the time from the date of first documented CR or PR to the first documented intracranial progression or death due to underlying cancer accoridng to modified RECIST 1.1, in patients with documented intracranial CR or PR before local treatment.
Group
Value
95% CI
COMBO450
5.6
3.6 – 7.5
Intracranial Progression-free Survival (iPFS) by RECIST 1.1Secondary· Throughout the study period, up to approximately 24 months
Defined as the time from the date of inclusion to the date of the first documented intracranial disease progression or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (modified RECIST version 1.1 criteria). The local Investigator's assessments was used for analyses. Those patients who were alive and had not progressed at the last follow-up, date of progression was censored at the date of the last follow-up. Patients with no additional image test other than baseline were censored the day after inclusion.
Group
Value
95% CI
COMBO450
8.5
6.4 – 11.8
Extracranial Progression-free Survival (ePFS) in Both CohortsSecondary· Throughout the study period, up to approximately 24 months
Defined as the time from the date of inclusion to the date of the first documented extracranial disease progression or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria). The local Investigator's assessments was used for analyses. Those patients who were alive and had not progressed at the last follow-up, date of progression was censored at the date of the last follow-up. Patients with no additional image test other than baseline were censored the day after inclusion.
Group
Value
95% CI
COMBO450
7.7
6.1 – 11.8
Intracranial Progression-free RatesSecondary· at 6 months (week 24), 12 months (week 48) and 24-month (week 96)
Proportion of patients free of intracranial progression assessed by modified RECIST at 6 months (week 24), 12 months (week 48) and 24-month (week 96) considering date of inclusion estimated through Kaplan-Meier method
6 months
Group
Value
95% CI
COMBO450
66.8
54.4 – 82.1
12 months
Group
Value
95% CI
COMBO450
29.5
18.2 – 47.6
24 months
Group
Value
95% CI
COMBO450
5.5
0.9 – 32
Overall SurvivalSecondary· Throughout the study period, up to approximately 24 months
Calculated as the time from date of inclusion to date of death due to any cause.
Group
Value
95% CI
COMBO450
15.9
10.7 – 21.4
Overall Survival RatesSecondary· at 6 months, 12 month and 24-month
Proportion of of patients alive at 6 months, 12 month and 24-month considering date of inclusion estimated using Kaplan-Meier.
Patients alive at the moment of the analysis were censored on the date of their last follow-up.
6 months
Group
Value
95% CI
COMBO450
91.6
84.1 – 99.8
12 months
Group
Value
95% CI
COMBO450
59.2
46.2 – 76
24 months
Group
Value
95% CI
COMBO450
15.5
6.7 – 35.8
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0Secondary· Throughout the study period, up to approximately 24 months
Number of patients experiencing treatment related adverse events. These events were graded accrding to CTCAE, a scale that ranges from 0 (less intense; no event) to 5 (death) .
Here we report the number of patients experiencing any grade toxicities and the number of patients experiencing high grade (grade 3-5) toxicities.
Any grade toxicities
Group
Value
95% CI
COMBO450
40
COMBO450
8
Grade 3-5 toxicities
Group
Value
95% CI
COMBO450
12
COMBO450
36
Change on Quality of Life at Week 8 in Both Cohorts Based on the EORTC QLQ 30 ScaleSecondary· 8 weeks
The EORTC QLQ-C30 questionnaire is validated for cancer. It is composed of 30 questions or items that assess QoL. The questionnaire is structured in 5 functional scales physical functioning, daily activities, emotional functioning, cognitive functioning and social functioning), 3 symptom scales (fatigue, pain and nausea, vomiting), 1 global health status scale, and 6 independent items (dyspnea, insomnia, anorexia, constipation, diarrhea and economic impact). Values between 1 and 4 (1: not at all, 2: a little, 3: quite, 4: a lot) are assigned according to the patient's responses to the item, on
Week 8
Group
Value
95% CI
COMBO450
85.5
48.6 – 99.4
Baseline
Group
Value
95% CI
COMBO450
78.4
29.3 – 98.7
Change on Quality of Life at Week 24 in Both Cohorts Based on the EORTC QLQ 30 ScaleSecondary· 24 weeks
The EORTC QLQ-C30 questionnaire is validated for cancer. It is composed of 30 questions or items that assess QoL. The questionnaire is structured in 5 functional scales physical functioning, daily activities, emotional functioning, cognitive functioning and social functioning), 3 symptom scales (fatigue, pain and nausea, vomiting), 1 global health status scale, and 6 independent items (dyspnea, insomnia, anorexia, constipation, diarrhea and economic impact). Values between 1 and 4 (1: not at all, 2: a little, 3: quite, 4: a lot) are assigned according to the patient's responses to the item, on
Week 24
Group
Value
95% CI
COMBO450
74.9
47.3 – 97.9
Baseline
Group
Value
95% CI
COMBO450
78.4
29.3 – 98.7
Extracranial Progression-free RatesSecondary· at 6 months (week 24), 12 months (week 48) and 24-month (week 96)
Proportion of patients free of extracranial progression assessed by modified RECIST at 6 months (week 24), 12 months (week 48) and 24-month (week 96) considering date of inclusion estimated through Kaplan-Meier method
6 months
Group
Value
95% CI
COMBO450
64.1
51.4 – 79.9
12 months
Group
Value
95% CI
COMBO450
31.2
19.6 – 49.6
24 months
Group
Value
95% CI
COMBO450
5.8
1 – 33.8
Adverse events — posted to ClinicalTrials.gov
Time frame: Throughout the study period, up to approximately 24 months.
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
COMBO450
Serious: 22/48 (46%)
Deaths: 33/48
Serious adverse events (28 terms)
Reaction
System
COMBO450
Seizure
Nervous system disorders
—
Anemia
Blood and lymphatic system disorders
—
Diarrhea
Gastrointestinal disorders
—
Headache
Nervous system disorders
—
Anaphylaxis
Immune system disorders
—
Creatinine increased
Investigations
—
Vomiting
Gastrointestinal disorders
—
Upper gastrointestinal hemorrhage
Gastrointestinal disorders
—
Pulmonary thromboembolism
Respiratory, thoracic and mediastinal disorders
—
Right pleural empyema by streptococcus constellatus
Phase II clinical trial, with two cohorts of patients included in parallel, all with melanoma BRAF mutated and brain metastases without previous local treatment in the brain. Cohort 1 will include patients with asymptomatic brain metastases and cohort 2 will include patients with symptomatic brain metastasis.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT05926960 — A Study Comparing 3 Study Medicines (Encorafenib, Binimetinib, Pembrolizumab) to 2 Study Medicines (Ipilimumab and Nivol
· Phase 2
· terminated
NCT04655157 — Safety and Efficacy in Participants With Metastatic BRAF-mutant Melanoma Treated With Encorafenib With and Without Binim
· Phase 1, PHASE2
· terminated
NCT04800822 — PF-07284892 in Participants With Advanced Solid Tumors
· Phase 1
· terminated
NCT03878719 — Study of the Combination of Binimetinib and Encorafenib in Adolescent Patients With Unresectable or Metastatic BRAF V600
· Phase 1
· terminated
NCT03915951 — An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer
· Phase 2
· completed
Other recruiting trials for Metastatic Melanoma
Currently open trials in the same condition.
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· Phase 1
· recruiting
NCT07237100 — Mirdametinib in Patients With Advanced NF1-mutant Melanoma
· Phase 2
· recruiting
NCT07086105 — A Study to Evaluate Adze1.C in Participants With Metastatic Melanoma
· Phase 1
· recruiting
NCT07112170 — Consolidative Use of Radiotherapy to Block Oligoprogression in Patients With Metastatic Melanoma
· NA
· recruiting
NCT06488365 — In Vivo Liquid Biopsy of Melanoma (Cytophone)
· NA
· recruiting
Other Grupo Español Multidisciplinar de Melanoma trials
Trials by the same sponsor.
NCT05542342 — Sitravatinib and Tislelizumab in Patients With Metastatic Uveal Melanoma With Liver Metastases.
· Phase 2
· completed
NCT02583516 — Clinical Trial to Evaluate the Efficacy of Vemurafenib in Combination With Cobimetinib (Continuous and Intermittent) in
· Phase 2
· completed
NCT02115139 — GEM STUDY: Radiation And Yervoy in Patients With Melanoma and Brain Metastases
· Phase 2
· completed
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Grupo Español Multidisciplinar de Melanoma
Last refreshed: 21 May 2025
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03898908.