Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity
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). . 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.
Timeline
- Start
- 2017-05-12
- Primary completion
- 2025-11-30
- Completion
- 2025-11-30
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Alectinib | Small molecule | 600 mg | — |
| Subject | Atezolizumab | Monoclonal antibody | 1200 mg | Intravenous |
| Subject | Trastuzumab emtansine | Other / unclassified | 3.6 mg/kg | Intravenous |
| Subject | Vemurafenib | Small molecule | 960 mg | — |