Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone

Dose limiting toxicities are defined as any Grade 3 or higher treatment-related (related to any study drug) toxicity that occurs during the DLT evaluation period. Number of participants with DLTs are reported.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Number of participants with abnormal vital signs and physical examinations reported as TEAEs are reported.

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.

Number of participants with abnormal electrocardiograms (ECGs) and echocardiograms (ECHOs) reported as TEAEs are reported.

Objective Response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). A confirmed CR is defined as two CRs that were separated by at least 28 days. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days. A CR is defined as disappearance of all target and non-target lesions, normalization of tumor marker level and any pathological lymph nodes selected as target lesions must have a reduction in short axis to less than 10 mm. A PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Duration of response: Duration from first documentation of OR to first documented PD or death due to any cause, whichever occurs first. CR: disappearance of all target and non-target lesions, normalization of tumor marker level and any pathological lymph nodes selected as target lesions must have a reduction in short axis to less than 10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of >= 5 mm, taking as reference smallest sum of diameters since treatment started including baseline sum of diameters.

Progression-free Survival is defined as duration from the start of treatment with study drug until the first documented PD or death, whichever comes first. PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of >= 5 mm, taking as reference smallest sum of diameters since treatment started including baseline sum of diameters. For participants who are alive and progression-free at the time of data cut-off for analysis, PFS was to be censored at the last tumor assessment date.

Overall survival (OS) is measured from the start of treatment until death. For participants who are alive at the end of study or lost to follow-up, OS was censored on the last date when participants are known to be alive.

Disease control is defined as confirmed CR or PR, or stable disease (SD) that was maintained for >= 12 weeks based on RECIST v1.1. A confirmed CR is defined as two CRs that were separated by at least 28 days. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 28 days. CR: disappearance of all target and non-target lesions, normalization of tumor marker level and any pathological lymph nodes selected as target lesions must have a reduction in short axis to less than 10 mm. A PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. A SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study.

Maximum observed plasma concentration of durvalumab after first dose is reported.

Maximum observed plasma concentration of durvalumab at steady state is reported.

Trough concentration of durvalumab pre-dose at steady state is reported.

The number of participants with positive serum antibodies to durvalumab post dosing are reported.