Phase II Safety Study of Vemurafenib Followed by Ipilimumab in Subjects With V600 BRAF Mutated Advanced Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety profile of vemurafenib, 960 mg, administered for 6 weeks, followed by ipilimumab monotherapy in patients with BRAF V600 mutated advanced/metastatic melanoma.

Official Title
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A Single Arm Open-Label Phase II Study of Vemurafenib Followed by Ipilimumab in Subjects With Previously Untreated V600 BRAF Mutated Advanced Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Ipilimumab
* Biological: Vemurafenib


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Key Inclusion Criteria: Men and women 18 years of age and older Histologic diagnosis of malignant melanoma tested positive for the BRAF V600 mutation Previously untreated unresectable Stage III or Stage IV melanoma Complete set of brain/neck, chest, abdomen/pelvis axial radiographs taken within 28 days of first dose of study drug Measurable melanoma by physical or radiographic examination Brain metastases stable after radiation for at least 1 month and off corticosteroid therapy for ≥30 days prior to enrollment Eastern Cooperative Oncology Group performance status of 0 or 1 Adequate hematologic parameters and renal and hepatic function Key Exclusion Criteria: Primary ocular melanoma Active brain metastases with symptoms or requiring corticosteroid treatment Any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies History of or current immunodeficiency disease, splenectomy, or splenic irradiation Prior anticancer therapy or investigational products <4 weeks prior to enrollment Prior therapy with a BRAF or MEK inhibitor and prior investigational anticancer immunotherapies; Prior therapies with immunosuppressive agents within the past 2 years Concomitant therapy with any anticancer or potent immunosuppressive agent, surgery, radiotherapy, other investigational anticancer therapies, or chronic use of systemic corticosteroids
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg<br>Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity. | Drug: Ipilimumab<br> <br> * Other names: BMS-734016;Biological: Vemurafenib<br> <br> * Other names: Zelboraf®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Skin Adverse Events (AEs) | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Drug-related=having certain, probable, possible, or unknown relationship to study drug. Grading criteria for AEs: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death. | From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Gastrointestinal Adverse Events (AEs) | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Drug-related=having certain, probable, possible, or unknown relationship to study drug. Grading criteria for AEs: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death. | From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first | 
| Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Hepatobiliary Adverse Events | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Drug-related=having certain, probable, possible, or unknown relationship to study drug. Grading criteria for AEs: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death. | From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first |