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

STATUS

Recruiting
End date

Aug 1, 2024
participants needed

92
sponsor

Haukeland University Hospital

Send

Updated on 6 April 2022

See if I qualify

metastatic melanoma

serum pregnancy test

measurable disease

melanoma skin

pembrolizumab

trametinib

dabrafenib

malignant melanoma of skin

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,

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.

Details

Condition	Melanoma
Treatment	Pembrolizumab, BGB324+pembrolizumab, BGB324+dabrafenib and trametinib, dabrafenib and trametinib
Clinical Study Identifier	NCT02872259
Sponsor	Haukeland University Hospital
Last Modified on	6 April 2022

How understandable was the trial content above?

Hard to understand

Easy to understand

Eligibility		Yes	No	Not Sure
Inclusion Criteria
	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)
Exclusion Criteria
	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
	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
	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)
	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
	Known active infection with human immunodeficiency virus (HIV), hepatitis B or C viruses (screening not required)
	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)
	Patients who have a history of hepatitis B infection are eligible provided they are hepatitis B surface antigen negative
	Ongoing infection requiring systemic treatment. Patients who are on prophylactic anti
	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
	infectives or who have been afebrile for 48 hours following the initiation of
	treatment are eligible
	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
	Any conditions which may have significant impact on absorption of BGB324 or dabrafenib
	Known hypersensitivity to pembrolizumab or BGB324 or excipients (including lactose intolerance)
	or trametinib from the gastrointestinal tract (including but not limited to
	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
	celiac disease or Crohn's disease, gastric or bowel resection)
	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

How to participate?

Step 1 Connect with a study center

Select a site
Send a message

You have contacted , on

Your message has been sent to the study team at ,

A copy of the message has been sent to your email

What happens next?

You can expect the study team to contact you via email or phone in the next few days.
Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Primary Contact

0/250

By sending a message, I agree that my data will be sent to a representative for the selected site and processed in accordance with this website's Privacy Policy (see link in footer).

Step 2 Get screened

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

Step 3 Enroll in the clinical study

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Step 4 Get your study results

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Browse trials for

malignant melanoma of skin

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Study Definition

Wikipedia

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