A Phase I Trial of Vemurafenib and Ipilimumab in Subjects With V600 BRAF Mutation-positive Metastatic Melanoma

During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone

时间窗: From first vemurafenib dose to day prior to first ipilimumab dose (28 days); Patients who never progressed from Lead-in to combination treatment (720 mg Alone): first dose to last dose + 90 days (approximately 2 years)

AEs graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death. Related=relationship to study drug reported as certain, probable, possible, or missing. Immune-related AEs (irAEs) characterized by potential association with inflammation and considered by investigator as drug related. Lead In Period: between the first vemurafenib dose and the day prior to the first ipilimumab dose.

During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib

时间窗: Combination drugs: Day 1 to last dose of drug + 90 days (approximately 2 years)

AEs graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death. Related=relationship to study drug reported as certain, probable, possible, or missing. AEs: onset on or after ipilimumab start and within 90 days of last dose. Immune-related AEs (irAEs) characterized by potential association with inflammation and considered by investigator as drug related. Day 1=first dose of ipilimumab.

Number of Participants With Hepatic Dose Limiting Toxicities (DLT) in Participants Treated With Concurrent Ipilimumab and Vemurafenib

时间窗: Day 1 to last dose of drug + 90 (approximately 2 years)

DLT defined as a \>= Grade 3 drug-related AE during induction with ipilimumab in combination with vemurafenib excluding: Grade 3 AE of tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor); Grade 3 cutaneous squamous cell carcinoma; Grade 3 photosensitivity that resolved to a Grade 1 or baseline within 15 days; Grade 3 immune-mediated events of the skin (rash, pruritis) or endocrine systems (hypothyroidism, hyperthyroidism, hypopituitarism, adrenal insufficiency, hypogonadism and cushingoid) that resolved to a Grade 1 or baseline within 28 days; a transient (resolving within 6 hours of onset) Grade 3 infusion-related AE. Hepatic=elevated aspartate aminotransferase and alanine aminotransferase. Maximum tolerable dose (MTD) was defined as the maximum dose of combination treatment that could be given to 6 subjects such that no more than 2 subjects experience DLT. Day 1=first day of concurrent therapy with ipilimumab and vemurafenib.