Ignite Creation Date:
2024-05-11 @ 8:31 AM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06401824
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-07
First Post:
2024-05-02
Brief Title:
Sacituzumab Govitecan and Bevacizumab for NSCLC Brain Metastases
Sponsor:
Maastricht University Medical Center
Organization:
Maastricht University Medical Center
Study Overview
Official Title:
A Single Arm Phase II Study Evaluating Intracranial Efficacy of Sacituzumab Govitecan SG With Bevacizumab in Patients With Active Asymptomatic Brain Metastases From Non-small Cell Lung Cancer NSCLC
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
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:
None
Brief Summary:
This study will evaluate whether the combination of sacituzumab govitecan SG and bevacizumab will result in shrinkage of brain metastases from patients with non-squamous non-small cell lung cancer NSCLC with disease progression on chemotherapy and immunotherapy
Detailed Description:
Historically the prognosis for patients with non-small cell lung cancer NSCLC brain metastases BM was poor but this paradigm is slowly shifting as current data with an immune checkpoint inhibitor ICI based regimen show that a subgroup of patients with BM can achieve long-term survival For patients with disease progression in the brain after platinum-doublet chemotherapy and ICI no good systemic treatment options exist and due to local treatments systemic therapy is often delayed Of note most of these patients also have extra-cranial disease progression which needs to be treated The current standard of care post chemo-ICI progression is docetaxel with dismal outcomes The same holds true for patients with NSCLC with an actionable genomic alteration Upon exhaustion of targeted therapies and platinum-doublet chemotherapy with or without ICI the standard of care is docetaxel with the same dismal outcomes Therefore new systemic therapies that are active systemically as well as intracranially are needed in this population Antibody-drug-conjugates ADC are promising new drugs and several have entered testing in randomized phase III trials In the majority of the trials evaluating ADCs patients with untreated BM were excluded Importantly Sacituzumab Govitecan SG a TROP2-ADC achieves therapeutic concentrations of SN-38 the active payload of SG in the CNS SG is evaluated versus docetaxel in the ongoing EVOKE-1 trial NCT05089734 but patients with untreated BM are excluded Preclinically SG combined with bevacizumab but not with cetuximab significantly improved survival over SG alone Bevacizumab combined with chemotherapy results in an impressive intracranial ORR of 61 Of note a possible pseudo response a marked decrease in contrast enhancement and oedema on MR imaging that often occurs after the initiation of bevacizumab therapy attributed to normalization of the blood-brain barrier was not taken into account Pharmacokinetic drug-drug interactions between bevacizumab and SG are not expected given the distinct proteolytic catabolism responsible for degradation of each monoclonal antibody moiety In addition SN-38 is metabolized by UGT1A1 which is not affected by bevacizumab Based on the data above it is of interest to also evaluate SG combined with bevacizumab in patients with BM from NSCLC This will be evaluated in patients with non-squamous non-small cell lung cancer NSCLC with disease progression on chemotherapy and immunotherapy
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