Phase 2 Study testing the COmbination of Vemurafenib With Cobimetinib in BRAF V600 mutated Melanoma Patients to Normalize LDH and Optimize immunotherapY with Nivolumab and Ipilimumab (COWBOY)

Phase 2 Study testing the COmbination of Vemurafenib With Cobimetinib in BRAF V600 mutated Melanoma Patients to Normalize LDH and Optimize immunotherapY with Nivolumab and Ipilimumab (COWBOY) - COWBOY

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-003279-23-NL

Enrollment

200

Registered

2019-11-26

Start date

2020-01-13

Completion date

Unknown

Last updated

2020-06-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Stage IV or unresectable stage III, BRAFV600E/K mutation positive melanoma, naïve for BRAF/MEK, PD-1/PD-L1 or CTLA-4 targeting therapy

Interventions

Trade Name: Opdivo Pharmaceutical Form: Concentrate for solution for infusion Trade Name: Yervoy Pharmaceutical Form: Concentrate for solution for infusion Trade Name: Cotellic Pharmaceutical Form:

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: In order to participate in this study, a subject must meet all of the following criteria: • Adults 18 years and older • World Health Organization (WHO) Performance Status 0-2 • Histologically or cytologically confirmed Stage IV, or unresectable stage III, BRAF V600E/K mutated melanoma • Measurable disease according to RECIST 1.1 • Signed and dated informed consent form • No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1 • No prior BRAFi and/ or MEKi therapy • No immunosuppressive medications • Screening laboratory values must meet the following criteria and should be obtained within 10 days prior to randomization: o WBC = 2.0x109/L, Neutrophils = 1.0x109/L, Platelets = 100 x109/L, Hemoglobin = 5.0mmol/L o Creatinine = 2x ULN o AST, ALT = 2.5 x ULN (=5 x ULN for patients with liver metastases) o Bilirubin =2 X ULN o LDH > ULN, =65 years) yes F.1.3.1 Number of subjects for this age range 50

Exclusion criteria

Exclusion criteria: Not applicable

Design outcomes

Primary

Measure	Time frame
Main Objective: To compare efficacy of upfront short-term vemurafenib + cobimetinib followed by ipilimumab + nivolumab (Arm A) versus standard ipilimumab + nivolumab treatment (Arm B) in patients with stage IV or unresectable stage III, BRAFV600E/K mutation positive melanoma, naïve for BRAF/MEK, PD-1/PD-L1 or CTLA-4 targeting therapy;Secondary Objective: • To describe duration of response and overall survival induced by vemurafenib + cobimetinib followed by the combination of ipilimumab + nivolumab (Arm A) as compared to ipilimumab + nivolumab t (Arm B) • To describe toxicity observed in the two study arms • To describe the rate of ongoing responses upon response-driven flat dose (240mg, q2w) nivolumab maintenance • To describe the rate of response after re-induction in case of progression after initial response-driven treatment break • To evaluate the changes in systemic immune competence;Primary end point(s): Compare the best overall response rate (BORR) according to RECIST 1.1 of both arms;Timepoint(s) of evaluation of this end point: Week 18 from start of treatment	—

Measure

Time frame

Main Objective: To compare efficacy of upfront short-term vemurafenib + cobimetinib followed by ipilimumab + nivolumab (Arm A) versus standard ipilimumab + nivolumab treatment (Arm B) in patients with stage IV or unresectable stage III, BRAFV600E/K mutation positive melanoma, naïve for BRAF/MEK, PD-1/PD-L1 or CTLA-4 targeting therapy;Secondary Objective: • To describe duration of response and overall survival induced by vemurafenib + cobimetinib followed by the combination of ipilimumab + nivolumab (Arm A) as compared to ipilimumab + nivolumab t (Arm B) • To describe toxicity observed in the two study arms • To describe the rate of ongoing responses upon response-driven flat dose (240mg, q2w) nivolumab maintenance • To describe the rate of response after re-induction in case of progression after initial response-driven treatment break • To evaluate the changes in systemic immune competence;Primary end point(s): Compare the best overall response rate (BORR) according to RECIST 1.1 of both arms;Timepoint(s) of evaluation of this end point: Week 18 from start of treatment

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Secondary

Measure	Time frame
Secondary end point(s): • Progression-free survival (PFS) according to RECIST 1.1 • Overall survival (OS) • Percentage of grade 3/4 toxicities according to CTCv4.03 • Percentage of ongoing response, percentage of patients requiring re-induction, response percentage upon re-induction • Changes in tumor-specific T cell responses;Timepoint(s) of evaluation of this end point: Progression and response related end-points will be assessed by CT every 6 weeks during treatment. Survival will be assessed every 12 weeks after the end of treatment. Safety will be assessed at each visit.	—

Measure

Time frame

Secondary end point(s): • Progression-free survival (PFS) according to RECIST 1.1 • Overall survival (OS) • Percentage of grade 3/4 toxicities according to CTCv4.03 • Percentage of ongoing response, percentage of patients requiring re-induction, response percentage upon re-induction • Changes in tumor-specific T cell responses;Timepoint(s) of evaluation of this end point: Progression and response related end-points will be assessed by CT every 6 weeks during treatment. Survival will be assessed every 12 weeks after the end of treatment. Safety will be assessed at each visit.

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Countries

Netherlands

Contacts

Public ContactTrialbureau Hematology-Oncology

Radboudumc

studies.onco@radboudumc.nl00312436 14794

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026