DARWIN2
Research type
Research Study
Full title
Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity A phase II, multi-centre, non-randomised, molecularly stratified trial for NSCLC patients to study tumour heterogeneity using genomic analysis
IRAS ID
191232
Contact name
Charles Swanton
Contact email
Sponsor organisation
University College London
Eudract number
2014-005456-25
Clinicaltrials.gov Identifier
Duration of Study in the UK
9 years, 4 months, 31 days
Research summary
Some Non-Small Cell Lung Cancers (NSCLC) are driven to grow by mutated proteins that can be targeted with a specific drug; these cancers are said to contain an actionable mutation. Treating patients, whose cancers contain actionable mutations with certain anti-cancer drugs may stop the cancer cells from dividing and growing. Some cancers do not contain actionable mutations and these may be better treated with antibody therapies that stimulate the patient’s own immune system to stop the cancer cells from dividing and growing.
The DARWIN2 trial is a phase II study investigating four different drugs. MPDL3280A is an immunotherapy for patients with cancers without an actionable mutation. For patients whose cancers have an actionable mutation we will investigate vemurafenib, alectinib and trastuzumab emtansine for the actionable variants BRAFV600, ALK/RET gene fusion and ERBB2 amplification respectively. The aim of this study is to see whether the immune targets of MPDL3280A and the actionable mutated proteins targeted by the other drugs alter the effectiveness of these medicines if they are present in all cancer cells throughout the tumour or just parts of the tumour. We think they will work better when they are found in all parts of the tumour.
Only patients registered in the TRACERx study or patients with two tissue/DNA primary tumour samples available, whose lung cancer has relapsed will be eligible for DARWIN2.
Tissue collected in DARWIN2 will also be compared to sequencing data from the primary tumour to see how the cancer has changed over time, and to see if there are any other genetic changes within the cancer during and after treatment.
The study will be undertaken throughout the UK at sites participating in the TRACERx study. It is expected that around 122 patients will be involved mainly depending on the number of patients whose cancers recur in the TRACERx study.
REC name
London - London Bridge Research Ethics Committee
REC reference
16/LO/1677
Date of REC Opinion
11 Nov 2016
REC opinion
Further Information Favourable Opinion