Advanced non-resectable (Stage IIIc) or metastatic (Stage IV) melanoma MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Code: BGB324
Pharmaceutical Form: Capsule, hard
Trade Name: Keytruda
Pharmaceutical Form: Powder for infusion
Trade Name: Keytruda
Pharmaceutical Form: Powder for infusion
Trade Name: Tafin
Sponsors
Helse Bergen HF, Haukeland universitetssjukehus
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1. Patients able to understand and willing to sign a written protocol specific informed consent and older than 18 years at the time of consent. 2. Histologically confirmed advanced cutaneous melanoma that is either non-resectable (Stage IIIc) or metastatic (Stage IV) with: a. At least one measurable lesion as defined by RECIST 1.1 on CT or MRI scan and b. Documented progression of =1 measurable lesion 3. ECOG performance status 0 to 2 at screening 4. Availability of fresh or archival tumour tissue sample suitable for evaluation of predictive biomarkers of response 5. Male patients with female partners of childbearing potential and female patients of childbearing potential willing to practice highly effective birth control while onfrom screening, throughout the study and for at least 3 months following the last dose of study treatment (and if female of childbearing potential, has a negative serum pregnancy test in the 7 days before the first dose of BGB324study treatment) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 67 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1.Prior first line systemic treatment for the treatment of Stage IIIb or Stage IIIc melanoma, including BRAF or MEK inhibitor 2.Symptomatic central nervous system metastatic lesions as determined by Investigator 3.History of malignancy other than melanoma within the last 2 years (basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; isolated elevation in prostate specific antigen in the absence of histological or radiographic evidence of prostate cancer is allowed) 4.History of or current active autoimmune diseases. Patients with vitiligo, or other non-serious autoimmune diseases based on the Investigator’s assessment, are NOT excluded 5.FOR BRAF pos PATS: History of retinal vein occlusion (RVO) or ongoing retinal pigment epithelial detachment (RPED) 6.History of the following cardiac conditions: a.Congestive cardiac failure of >Grade 2 severity according to the New York Heart Association (defined as symptomatic at less than ordinary levels of activity) b.Ischemic cardiac event including myocardial infarction within 3 months prior to first dose of study treatment c.Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension or need to change medication within 6 weeks of provision of consent due to lack of disease control d.History or presence of sustained bradycardia (=55 bpm), left bundle branch block, cardiac pacemaker or ventricular arrhythmia. Note: Patients with a supraventricular arrhythmia requiring medical treatment, but with a normal ventricular rate are eligible e.Family history of long QTc syndrome; personal history of long QTc syndrome or previous drug-induced QTc prolongation 7.Abnormal left ventricular ejection fraction on echocardiography or Multi Gated Acquisition (MUGA) Scan (MUGA) (less than the lower limit of normal for a patient of that age at the treating institution or 450ms 10.Inadequate organ function as defined by the following laboratory values: a.Haematological: absolute neutrophil count =1.5 x 109/L, platelets =100 x 109/L, haemoglobin =9.0 g/dL b.Renal: serum creatinine =1.5 x institutional upper limit of normal (ULN) and estimated glomerular filtration rate of =50 mL/minute c.Hepatic: total bilirubin =1.5 x institutional ULN, alanine transaminase and aspartate transaminase =2.5 x institutional ULN or =5.0 x institutional ULN if liver metastases are present d.Coagulation: international normalized ratio or prothrombin time and activated partial thromboplastin time =1.5 x institutional ULN if not using anticoagulants (if patient is receiving anticoagulant therapy value must be within therapeutic range for the condition being treated) 11.Ongoing infection requiring systemic treatment. Patients who are on prophylactic anti infectives or who have been afebrile for 48 hours following the initiation of treatment are eligible 12.Known active infection with human immunodeficiency virus (HIV), hepatitis B or C viruses (screening not required) •Patients who have a history of hepatitis B infection are eligible provided they are hepatitis B surface antigen negative •Patients who have a history of hepatitis C infection are eligible provided they have no evi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 To evaluate BGB324 safety in combination with dabrafenib/trametinib and to select the dose level of BGB324 for combination treatment with dabrafenib/trametinib in patients with advanced melanoma. Part 2 To evaluate safety and efficacy of pembrolizumab and dabrafenib/trametinib in combination with BGB324 compared to pembrolizumab and dabrafenib/trametinib alone as first line treatment in patients with advanced melanoma. Part 3 To explore safety and efficacy of pembrolizumab or dabrafenib/trametinib in combination with BGB324 and pembrolizumab or dabrafenib/trametinib alone as second line treatment in BRAF+ patients with advanced melanoma failing first line treatment in Part 2 of the study. ;Secondary Objective: Part 1 and 2: - PK of BGB324 in combination with pembrolizumab and dabrafenib/trametinib compared the PK of BGB324 monotherapy using data from previous clinical studies with BGB324 - PK of dabrafenib in combination With BGB324 compared to PK for dabrafenib administered in dabrafenib/trametinib combination (historical data) - long term combined safety and efficacy profile of combination treatment of BGB324 and standard therapy to standard treatment alone Part 3: To evaluate safety and efficacy of BGB324 in combination with pembrolizumab or dabrafenib/trametinib as second line treatment in melanoma patients failing first line treatment with dabrafenib/trametinib or pembrolizumab respectively in combination with BGB324 as first line treatment in patients BRAF+ at randomisation Exploratory - evaluate the predictive value of candidate biomarkers in blood, urine or tissue - assess effects of BGB324 on biological markers - Health-related Quality of Life of melanoma patients ;Primary end point(s): Primary Efficacy Endpoint Objective Response Rate (ORR) assessed according to RECIST Version 1.1 ;Timepoint(s) of evaluation of this end point: Primary Efficacy Endpoint Objective Response Rate (ORR) assessed according to RECIST Version 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints • Progression Free Survival (PFS) • Duration of response- defined as time from objective response until disease progression (clinical or RECIST confirmed) • Overall Survival (OS) Exploratory Efficacy Endpoints • ORR assessed according to irRC • Biomarkers • HRQoL using the EuroQoL instrument and European Organisation for Research and Treatment Cancer (EORTC) quality of life questionnaire core (QLQ-C30) Pharmacokinetic Endpoints Plasma concentrations of BGB324 and dabrafenib, Area Under the Curve within a dosing interval (AUC0-T) and Average Concentration (Cav) estimated at steady state. Safety Endpoints Safety endpoints are based on continuous monitoring of adverse events and other safety parameters (laboratory safety assessments, vital signs 12-lead ECGs, physical examination and skin examination and performance status using the ECOG score). ;Timepoint(s) of evaluation of this end point: ongoing evaluation | — |
Countries
Norway
Contacts
Public ContactOddbjørn Straume
Helse Bergen HF, Haukeland universitetssjukehus
Outcome results
None listed