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

Phase 2

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg	Vemurafenib	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.
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg	Ipilimumab	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Skin Adverse Events (AEs)	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	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Hepatobiliary Adverse Events	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	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.
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Gastrointestinal Adverse Events (AEs)	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	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.

Locations (14): University Hospitals Of Cleveland
🇺🇸
Cleveland, Ohio, United States
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Baptist Cancer Institute
🇺🇸
Jacksonville, Florida, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
University Hospitals
🇺🇸
Cleveland, Ohio, United States
University Of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Orlando Health, Inc
🇺🇸
Orlando, Florida, United States
Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Duke University Hospital
🇺🇸
Durham, North Carolina, United States
Dumc
🇺🇸
Durham, North Carolina, United States
Beverly Hills Cancer Center
🇺🇸
Beverly Hills, California, United States
Mount Sinai School Of Medicine
🇺🇸
New York, New York, United States