MelanomaPhase 1/2NCT02872259
BGB324 in Combination With Pembrolizumab or Dabrafenib/Trametinib in Metastatic Melanoma
A Phase 1/2 study testing BGB324+pembrolizumab, BGB324+dabrafenib and trametinib and pembrolizumab in people with Melanoma, run by Haukeland University Hospital at 5 sites in Norway.
Trial 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, Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- BGB324+pembrolizumab, BGB324+dabrafenib and trametinib and pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 5 sitesNorway
- Study dates
- 13 Feb 2017to 23 May 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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:
Show all 31Show fewer
- 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:
- Haematological: absolute neutrophil count ≤1.5 x 109/L, platelets ≤100 x 109/L, haemoglobin ≤9.0 g/dL
- Renal: serum creatinine ≥1.5 x institutional upper limit of normal (ULN) and creatinine clearance ≥50 mL/minute
- Hepatic: total bilirubin ≥1.5 x institutional ULN, alanine transaminase (ALT) and aspartate transaminase (AST) ≥2.5 x institutional ULN or ≥5.0 x institutional ULN if liver metastases are present
- Coagulation: international normalised 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)
- 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
- 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 evidence of hepatitis C ribonucleic acid using a quantitative polymerase chain reaction assay at least 6 months after completing treatment for hepatitis C infection
- Any conditions which may have significant impact on absorption of BGB324 or dabrafenib or trametinib from the gastrointestinal tract (including but not limited to, celiac disease or Crohn's disease, gastric or bowel resection)
- Any severe or uncontrolled medical conditions which may jeopardise patient safety, compliance with the protocol, or interpretation of study results in the opinion of the Investigator
- Current or recent (within last year) systemic treatment with immunosuppressive or immunomodulating agents (including systemic steroids intended for immunosuppressive effect), or other medications known to have significant impact on the immune system. Topical agents and inhaled steroids are permitted
- Treatment with any medication with a narrow therapeutic index which is predominantly metabolised by cytochrome P450 (CYP)3A4 and cannot be stopped before the first dose of study treatment
- Known hypersensitivity to pembrolizumab or BGB324 or excipients (including lactose intolerance)
- ONLY FOR BRAF POSITIVE PATIENTS: Known hypersensitivity to dabrafenib or trametinib (including lactose intolerance)
- Treatment with histamine receptor 2 inhibitors, proton pump inhibitors or antacids in the 7 days before the first dose of study treatment
- Treatment with more than 40 mg prednisolone (or equivalent dose of systemic corticosteroid) which cannot be discontinued up to one week prior to starting BGB324. During the study this exclusion criteria is only applicable for patients receiving BGB324.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Norway5 sites
Haukeland University Hospital
Bergen, 5021
Akershus Univerisity Hospital
Lørenskog, 1478
Oslo University Hospital, Radiumhospitalet
Oslo, 0424
University Hospital of North Norway
Tromsø, 9038
St. Olavs Hospital
Trondheim, 7006
About this study
Official title: A Phase Ib/II Randomised Open Label Study of BGB324 in Combination With Pembrolizumab or Dabrafenib/Trametinib Compared to Pembrolizumab or Dabrafenib/Trametinib Alone, in Patients With Advanced Non-resectable (Stage IIIc) or Metastatic (Stage IV) Melanoma
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,
Read the detailed description
This is an investigator initiated randomized randomized clinical phase 1b/2 clinical trial comparing safety and efficacy of the Axl inhibitor BGB324 in combination with pembrolizumab or dabrafenib+trametinib with that of pembrolizumab or dabrafenib+trametinib alone. Patients with non-resectable stage III or stage IV melanoma will be stratified based on BRAF mutation and tumor load to start dabrafenib+trametinib (BRAF mutation and high tumor load) or pembrolizumab (BRAF wild type or BRAF mutation and low tumor load) in first line. The patients will be randomized 2:1 to receive BGB324 in combination with pembrolizumab or dabrafenib+trametinib or to receive pembrolizumab or dabrafenib+trametinib alone. A 3+3 dose escalation will be performed for the combination of BGB324 and dabrafenib+trametinib. There is a major focus on predictive markers of treatment response evaluated in blood samples and biopsies.
- Conditions
- Melanoma
- Being tested
- BGB324+pembrolizumab, BGB324+dabrafenib and trametinib, pembrolizumab, dabrafenib and trametinib
- Keywords
- metastatic melanoma, advanced Non-resectable melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BGB324+pembrolizumabDrug
Also called Keytruda
Combination
BGB324+dabrafenib and trametinibDrug
Also called Tafinlar, Mekinist
Combination
pembrolizumabDrug
Also called Keytruda
Monotherapy
dabrafenib and trametinibDrug
Also called Tafinlar, Mekinist
Combination
| Study group | Role | What they receive |
|---|---|---|
| BGB324 + pembrolizumab | Experimental | BGB324 capsules, 200 mg once daily + pembrolizumab 2 mg/kg IV every 3. week
Treatment until disease progression, or unacceptable toxicity Receives: 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 Receives: Drug: BGB324+dabrafenib and trametinib |
| pembrolizumab | Active comparator | Pembrolizumab 2 mg/kg IV every 3. week
Treatment until disease progression, or unacceptable toxicity Receives: 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 Receives: Drug: dabrafenib and trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) assessed according to RECIST Version 1.1
Measured: through study completion, an average of 1 year
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: through study completion, an average of 1 year
Secondary outcomes (3)
Progression Free Survival (PFS)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
Measured: ongoing evaluation, assessed up to 5 years
Duration of response
through study completion, an average of 1 year
Measured: ongoing evaluation, an average of 1 year
Overall Survival (OS)
through study completion, an average of 2 year
Measured: ongoing evaluation, an average of 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2016 (estimated)
- Study start13 Feb 2017
- Primary completion23 May 2024
- Study completion23 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- BerGenBio ASA
- Responsible party
- Sponsor
- Investigators
- Oddbjørn Straume, MD PhD, Principal investigator, Haukeland University Hospital, 5021 Bergen, Norway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02872259
- Sponsor's protocol ID
- 2015/1155
- Status last verified
- Jan 2025
- First submitted
- 28 Jun 2016
- Last updated
- 14 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Randomised Open Label Study of BGB324 in Combination With Pembrolizumab or Dabrafenib/Trametinib Compared to Pembrolizumab or Dabrafenib/Trametinib Alone, in Patients With Advanced Non-resectable (Stage IIIc) or Metastatic (Stage IV) Melanoma
- ClinicalTrials.gov ID
- NCT02872259
- Acronym / sponsor ID
- 2015/1155
- Conditions
- Melanoma
- Keywords
- metastatic melanoma, advanced Non-resectable melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Collaborators
- BerGenBio ASA
- Study start
- 13 Feb 2017 (actual)
- Primary completion
- 23 May 2024 (actual)
- Study completion
- 23 May 2024 (actual)
- First posted
- 19 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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,
Detailed description
This is an investigator initiated randomized randomized clinical phase 1b/2 clinical trial comparing safety and efficacy of the Axl inhibitor BGB324 in combination with pembrolizumab or dabrafenib+trametinib with that of pembrolizumab or dabrafenib+trametinib alone. Patients with non-resectable stage III or stage IV melanoma will be stratified based on BRAF mutation and tumor load to start dabrafenib+trametinib (BRAF mutation and high tumor load) or pembrolizumab (BRAF wild type or BRAF mutation and low tumor load) in first line. The patients will be randomized 2:1 to receive BGB324 in combination with pembrolizumab or dabrafenib+trametinib or to receive pembrolizumab or dabrafenib+trametinib alone. A 3+3 dose escalation will be performed for the combination of BGB324 and dabrafenib+trametinib. There is a major focus on predictive markers of treatment response evaluated in blood samples and biopsies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BGB324 + pembrolizumab | Experimental | Drug: BGB324+pembrolizumabBGB324 capsules, 200 mg once daily + pembrolizumab 2 mg/kg IV every 3. week Treatment until disease progression, or unacceptable toxicity |
| BGB324 + dabrafenib and trametinib | Experimental | Drug: BGB324+dabrafenib and trametinibBGB324 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 |
| pembrolizumab | Active comparator | Drug: pembrolizumabPembrolizumab 2 mg/kg IV every 3. week Treatment until disease progression, or unacceptable toxicity |
| dabrafenib and trametinib | Active comparator | Drug: dabrafenib and trametinibDabrafenib capsules:150 mg twice daily Trametinib tablets: 2 mg once daily Treatment until disease progression, or unacceptable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- 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)
Key exclusion criteria (31 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BGB324+pembrolizumabAlso: KeytrudaCombination | Drug | BGB324 + pembrolizumab |
| BGB324+dabrafenib and trametinibAlso: Tafinlar, MekinistCombination | Drug | BGB324 + dabrafenib and trametinib |
| pembrolizumabAlso: KeytrudaMonotherapy | Drug | pembrolizumab |
| dabrafenib and trametinibAlso: Tafinlar, MekinistCombination | Drug | dabrafenib and trametinib |
Primary outcome
Objective Response Rate (ORR) assessed according to RECIST Version 1.1
Time frame: through study completion, an average of 1 year
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: through study completion, an average of 1 year
3 secondary outcomes
Progression Free Survival (PFS)
Time frame: ongoing evaluation, assessed up to 5 years
Duration of response
Time frame: ongoing evaluation, an average of 1 year
Overall Survival (OS)
Time frame: ongoing evaluation, an average of 2 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oddbjørn Straume, MD PhD principal investigator
Haukeland University Hospital, 5021 Bergen, Norway
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BGB324+pembrolizumab, BGB324+dabrafenib and trametinib and pembrolizumab in people with Melanoma, run by Haukeland University Hospital at 5 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) assessed according to RECIST Version 1.1 (time frame: through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2025; AzTrials last refreshed its copy on 8 Nov 2026.