Ignite Creation Date:
2024-05-06 @ 3:34 AM
Last Modification Date:
2024-10-26 @ 11:35 AM
Study NCT ID:
NCT02314481
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-12-04
First Post:
2014-12-05
Brief Title:
Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity
Sponsor:
University College London
Organization:
University College London
Study Overview
Official Title:
Deciphering Antitumour Response and Resistance With INtratumour Heterogeneity - DARWINII
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DARWINII
Brief Summary:
DARWIN II is a multi-arm non-randomised phase II trial Eligible patient will be those who relapse with NSCLC clinical trialsgov 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 ie non-squamous or squamous
Patients with BRAFV600 mutations HER2 Amplification ALKRET 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
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 ie non-squamous or squamous
Patients with BRAFV600 mutations HER2 Amplification ALKRET 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
Detailed Description:
DARWIN II is an exploratory phase II study examining the role of intra-tumour heterogeneity and predicted neo-antigens on the anti-tumour activity of anti-PDL1 immunotherapy
It will examine how clonal dominance and intratumour heterogeneity influence outcomes after treatment offering a unique opportunity to decipher mechanisms of resistance to immunotherapy with anti-PDL1 These data will help improve future study design by developing greater understanding of patient selection for immunotherapies in patients with NSCLC The relationship between intratumour heterogeneity and cfDNACTCs will also be explored in DARWIN II which may develop tools for patient selection and monitoring to be examined further in future studies Results from DARWIN II will help to identify a biomarker for anti-PD-L1 therapy which could be used for patient stratification in future phase III trials of molecules targeting this T-cell inhibitory checkpoint DARWIN II will also provide preliminary data on efficacy of MPDL3280A which could be used to design randomised studies
This is a multicentre non-randomised phase II study based on patients with relapsed NSCLC who have provided a biopsy sample at the time of relapse
The study arms
Arm 1 Patients without an actionable mutation - MPDL3280A atezolizumab monotherapy or in combination with chemptherapy
Arm 2 BRAFV600 - vemurafenib
Arm 3 ALKRET gene rearrangement - alectinib
Arm 4 HER2 Amplification - trastuzumab emtansine
Arms 2-4 are closed to further recruitment as of 25th May 2021
It will examine how clonal dominance and intratumour heterogeneity influence outcomes after treatment offering a unique opportunity to decipher mechanisms of resistance to immunotherapy with anti-PDL1 These data will help improve future study design by developing greater understanding of patient selection for immunotherapies in patients with NSCLC The relationship between intratumour heterogeneity and cfDNACTCs will also be explored in DARWIN II which may develop tools for patient selection and monitoring to be examined further in future studies Results from DARWIN II will help to identify a biomarker for anti-PD-L1 therapy which could be used for patient stratification in future phase III trials of molecules targeting this T-cell inhibitory checkpoint DARWIN II will also provide preliminary data on efficacy of MPDL3280A which could be used to design randomised studies
This is a multicentre non-randomised phase II study based on patients with relapsed NSCLC who have provided a biopsy sample at the time of relapse
The study arms
Arm 1 Patients without an actionable mutation - MPDL3280A atezolizumab monotherapy or in combination with chemptherapy
Arm 2 BRAFV600 - vemurafenib
Arm 3 ALKRET gene rearrangement - alectinib
Arm 4 HER2 Amplification - trastuzumab emtansine
Arms 2-4 are closed to further recruitment as of 25th May 2021
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None