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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 2

Conditions: Melanoma

Treatments: Biological: Vemurafenib; Drug: Ipilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01673854

CA184-240

2012-002054-24 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 70 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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70 participants in 1 patient group

Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Ipilimumab

Biological: Vemurafenib