BGB324 in Combination With Pembrolizumab or Dabrafenib/Trametinib in Metastatic Melanoma

NCT02872259 | Completed Phase 1 DMC

• 1 other identifier: 2015/1155
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of the study is to assess the safety and efficacy of BGB324 given together with standard treatment, pembrolizumab or dabrafenib and trametinib, compared to standard treatment alone,

Conditions

Melanoma

Keywords

metastatic melanoma; advanced Non-resectable melanoma

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) assessed according to RECIST Version 1.1

  through study completion, an average of 1 year

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  through study completion, an average of 1 year

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  ongoing evaluation, assessed up to 5 years

• Duration of response

  ongoing evaluation, an average of 1 year

• Overall Survival (OS)

  ongoing evaluation, an average of 2 year

Study Arms (4)

BGB324 + pembrolizumab

EXPERIMENTAL

BGB324 capsules, 200 mg once daily + pembrolizumab 2 mg/kg IV every 3. week Treatment until disease progression, or unacceptable toxicity

Drug: BGB324+pembrolizumab

BGB324 + dabrafenib and trametinib

EXPERIMENTAL

BGB324 capsules: Dose finding part of the study will determine if 100 mg once daily should be used for main part of the study or if 200 mg once daily once daily should be used. Dabrafenib capsules: 150 mg twice daily Trametinib tablets: 2 mg once daily Treatment until disease progression, or unacceptable toxicity

Drug: BGB324+dabrafenib and trametinib

pembrolizumab

ACTIVE COMPARATOR

Pembrolizumab 2 mg/kg IV every 3. week Treatment until disease progression, or unacceptable toxicity

Drug: pembrolizumab

dabrafenib and trametinib

ACTIVE COMPARATOR

Dabrafenib capsules:150 mg twice daily Trametinib tablets: 2 mg once daily Treatment until disease progression, or unacceptable toxicity

Drug: dabrafenib and trametinib

Interventions

BGB324+pembrolizumab DRUG

Combination

Also known as: Keytruda

BGB324 + pembrolizumab

BGB324+dabrafenib and trametinib DRUG

Combination

Also known as: Tafinlar, Mekinist

BGB324 + dabrafenib and trametinib

pembrolizumab DRUG

Monotherapy

Also known as: Keytruda

pembrolizumab

dabrafenib and trametinib DRUG

Combination

Also known as: Tafinlar, Mekinist

dabrafenib and trametinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients able to understand and willing to sign a written protocol specific informed consent and 18 years or older at the time of consent
• Histologically confirmed advanced cutaneous melanoma that is either non-resectable (Stage IIIc) or metastatic (Stage IV) with:
• At least one measurable lesion as defined by RECIST 1.1 on CT or MRI scan and
• Documented progression of ≥1 measurable lesion
• ECOG score 0 to 2 at screening
• Availability of fresh or archival tumour tissue sample suitable for evaluation of predictive biomarkers of response
• Male patients with female partners of childbearing potential and female patients of childbearing potential willing to practice highly effective birth control from 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 study treatment)

You may not qualify if:

• Prior first line systemic treatment for the treatment of Stage IIIb or Stage IIIc melanoma, including BRAF or MEK inhibitor (adjuvant immunomodulating agent treatment more than 6 months prior to first dose of study treatment is allowed)
• Symptomatic central nervous system metastatic lesions as determined by the Investigator (patients with radiographically stable, asymptomatic lesions previously irradiated or surgically resected are eligible provided there is no need for systemic corticosteroids and treatment was completed at least 4 weeks before the first dose of study treatment)
• 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)
• History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (e.g. Guillain-Barré syndrome). Patients with vitiligo, or other non-serious autoimmune diseases based on the Investigator's assessment, are NOT excluded
• ONLY FOR BRAF POSITIVE PATIENTS: History of retinal vein occlusion (RVO) or ongoing retinal pigment epithelial detachment (RPED)
• History of the following cardiac conditions:
• Congestive cardiac failure of \>Grade 2 severity (see Appendix 1) according to the New York Heart Association (defined as symptomatic at less than ordinary levels of activity)
• Ischemic cardiac event including myocardial infarction within 3 months prior to first dose of study treatment
• Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (i.e. sustained systolic blood pressure \>160 mmHg or diastolic blood pressure \>90 mmHg), or need to change medication within 6 weeks of provision of consent due to lack of disease control
• 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
• Family history of long QTc syndrome; personal history of long QTc syndrome or previous drug-induced QTc prolongation
• Known abnormal left ventricular ejection fraction on echocardiography or Multi Gated Acquisition (MUGA) scan (less than the lower limit of normal for a patient of that age at the treating institution or \<45%, whichever is lower)
• Current treatment with any agent known to cause Torsade de Points which cannot be discontinued at least five half-lives or two weeks prior to the first dose of study treatment
• Screening 12-lead ECG with a measurable QTc interval calculated according to Fridericia's correction (QTcF) \>450 ms
• Inadequate organ function as defined by the following laboratory values:

Sponsors & Collaborators

• Haukeland University Hospital: lead
• BerGenBio ASA: collaborator

Study Sites (5)

Haukeland University Hospital

Bergen, 5021, Norway

Location

Akershus Univerisity Hospital

Lørenskog, 1478, Norway

Location

Oslo University Hospital, Radiumhospitalet

Oslo, 0424, Norway

Location

University Hospital of North Norway

Tromsø, 9038, Norway

Location

St. Olavs Hospital

Trondheim, 7006, Norway

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; trametinib; dabrafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Oddbjørn Straume, MD PhD

  Haukeland University Hospital, 5021 Bergen, Norway

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: August 19, 2016
• Study Start: February 13, 2017
• Primary Completion: May 23, 2024
• Study Completion: May 23, 2024
• Last Updated: January 14, 2025

Record last verified: 2025-01

Locations

NO (5)