Comparative Effectiveness of Targeted Therapies in BRAF Positive Metastatic Melanoma in the US (OCEANMIST)

Comparative Effectiveness of Different Targeted Therapies for BRAF-mutated Unresectable/Metastatic Melanoma in the United States

This study aims to compare real-world effectiveness of BRAF/MEK inhibitors in BRAF-mutant metastatic melanoma patients in the United States by line of therapy.

The Flatiron Health electronic health record (EHR) data from US cancer clinics will be used for this retrospective database analysis.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Encorafenib; Drug: Binimetinib; Drug: Vemurafenib; Drug: Cobimetinib; Drug: Dabrafenib; Drug: Trametinib

• Study Type: Observational
• Enrollment (Actual): 716

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10017
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will be metastatic melanoma patients receiving targeted combination therapies derived from an anonymized Flatiron Health data combined with patient data from COLUMBUS trial data

Description

Inclusion Criteria:

• Diagnosed with melanoma based on International Classification of Disease 9th and 10th Revisions (ICD-9: 172.x; ICD-10: C43x, D03x) and ≥2 visits on different days in the Flatiron database on or after January 1, 2011.
• Clinically confirmed diagnosis of melanoma with pathologic stages III or IV at initial diagnosis or earlier stage disease with a first locoregional or distant recurrence on or after January 1, 2011.
• Age ≥18 years at the time of advanced melanoma diagnosis.
• Evidence of ≥1 BRAF positive test result at any time based on laboratory or genetic analysis results.

Exclusion Criteria:

-• Patients with prior BRAF- or MEK-inhibitor therapy

• Patients with ECOG performance status ≥ 2 (at the time of randomization for patients from COLUMBUS, during the baseline period for patients in Flatiron EHR)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Encorafenib + binimetinib; Encorafenib 450 mg once a day (QD) Binimetinib 45 mg twice a day (BID)	Drug: Encorafenib; 450 mg QD; Other Names: Administration route: Oral; Drug: Binimetinib; 45 mg BID; Other Names: Administration route: Oral
Dabrafenib + trametinib; Dabrafenib 150 mg twice a day (BID) Trametinib 2 mg once a day (QD)	Drug: Dabrafenib; 150 mg BID; Other Names: Administration route: Oral; Drug: Trametinib; 2 mg QD; Other Names: Administration route: Oral
Vemurafenib + Cobimetinib; Vemurafenib 960 mg twice a day (BID) for 28 days of 28 day cycle Cobimetinib 60 mg once a day (QD) for 21 days of 28 day cycle	Drug: Vemurafenib; 960 mg BID for 28 days/cycle; Other Names: Administration route: Oral; Drug: Cobimetinib; 60 mg QD for 21 days/cycle; Other Names: Administration route: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	As per COLUMBUS trial, OS was defined as the time from the date of randomization to the date of death due to any cause; if death was not observed, participants were censored at the date of last contact or the data analysis cut-off date, whichever occurred first. As per Flatiron EHR, OS was defined as the time from the index date to the date of death; participants without a date of death were censored at their last known activity date or the end of the follow-up period, whichever occurred first. Index date in each treatment group was defined as the date of treatment initiation. Kaplan-Meier analyses was used for analysis.	COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	COLUMBUS:PFS=time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurred first; PD:at least 20 percentage (%) increase in the sum of diameter of all measured target lesions, reference to the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimiter square (mm2) or the appearance of 1 or more new lesion, if a participant did not have an event at the analysis cut-off date, PFS was censored at the date of the last adequate tumour assessment. Flatiron:PFS=time from the index date to either the date of first PD event or death in the absence of progression; participants without PD or death were censored at the last date the participant could have been assessed for progression or the data analysis cut-off date, whichever occurred first. Index date was =the date of treatment initiation.	COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2022
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: February 18, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Metastatic melanoma; BRAF-mutant
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Vemurafenib; Trametinib; Dabrafenib
• Other Study ID Numbers: C4221028; OCEANMIST (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.