Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity
Status:
Recruiting
Trial end date:
2025-11-01
Target enrollment:
Participant gender:
Summary
DARWIN II is a multi-arm non-randomised phase II trial, Eligible patient will be those who
relapse with NSCLC (clinical trials.gov ref. NCT02183883). Patients must have at least two
tissue/DNA samples of their disease available for sequencing.
The trial will investigate assess if intra-tumour heterogeneity (clonal vs subclonal
actionable mutation) is associated with PFS.
Patients without an actionable mutation will receive MPDL3280A (atezolizumab), a monoclonal
antibody targeting anti-PDL1, as monotherapy or in combination with chemotherapy, The options
for combination therapy will vary depending on the histology of the NSCLC (i.e. non-squamous
or squamous).
Patients with BRAFV600 mutations, HER2 Amplification, ALK/RET gene rearrangements will be
enrolled into arms treating with vemurafenib, trastuzumab emtansine and alectinib
respectively.
DARWIN II will include extensive exploratory biomarker analysis to investigate a number of
genomic and immune markers that may predict response to MPDL3280A (atezolizumab) and help
guide future clinical trial design.