Ignite Creation Date:
2024-05-06 @ 3:44 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04739202
Status:
UNKNOWN
Last Update Posted:
2021-03-29
First Post:
2021-01-13
Brief Title:
Personalized Targeted IMMUNOtherapy-based Regimens in Recurrent GASTric Adenocarcinoma IMMUNOGAST
Sponsor:
Hospices Civils de Lyon
Organization:
Hospices Civils de Lyon
Study Overview
Official Title:
An Umbrella Phase 2 Trial to Assess Personalized Targeted IMMUNOtherapy-based Regimens in Recurrent AdvancedMetastatic GASTric Adenocarcinoma Patients
Status:
UNKNOWN
Status Verified Date:
2021-03
Last Known Status:
RECRUITING
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:
IMMUNOGAST
Brief Summary:
For patients with advancedmetastatic gastric adenocarcinomas in progression after a first line chemotherapy comprising platinum and fluoropyrimidine the reported second line treatments are 1 paclitaxel combined with ramucirumab overall response rate ORR 25 median progression free survival PFS 29 months median overall survival OS 59 months or paclitaxel alone ORR 14 median PFS 29 months median OS 59 months 2 docetaxel ORR 7 median OS 52 months or 3 irinotecan ORR 0 median OS 40 months
These numbers demonstrate the poor prognosis of this disease and the unmet medical need for innovative therapeutic strategies
Cancer Genome Atlas TCGA mapped a genomic landscape of gastric adenocarcinomas and identified 4 sub-types
Tumor positive for Epstein-Barr virus EBV 8 which display recurrent PIK3CA mutations extreme DNA hypermethylation and amplification of JAK2 ErbB2 PD-L1 and PD-L2
Microsatellite instable tumors MSI-high 22 which show elevated mutation rates including mutations of genes encoding targetable oncogenic signaling proteins PIK3CA ErbB2 ErbB3 and EGFR
Genomically stable tumors 20 which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins
Tumors with chromosomal instability 50 which show marked aneuploidy and focal amplification of receptor tyrosine kinases and VEGFA
Most of diffuse-type gastric adenocarcinomas were classified in genomically stable tumors This subgroup of cancers accounting for about 20 to 30 of gastric adenocarcinomas is associated with particularly poor prognosis and resistance to chemotherapy A proteomic landscape of diffuse-type gastric adenocarcinomas was recently reported
Pembrolizumab an anti-PDL1 drug granted with an accelerated approval by FDA in September 2017 exhibited promising activity in gastric adenocarcinoma patients previously treated with 1 or 2 lines of chemotherapy ORR116 median PFS 20 months median OS 56 months especially in those with PDL1 positive tumors ORR227 The tumor response was particularly high in patients with MSI-high tumor ORR571 However the preliminary outcomes of the phase III KEYNOTE-061 trial NCT02370498 recently released in the press suggest that pembrolizumab was not superior to paclitaxel in 592 patients with advanced gastric or gastroesophageal junction adenocarcinoma whose disease progressed after first-line treatment with platinum and fluoropyrimidine doublet therapy the hazard ratio HR for OS was 082 95 confidence interval 066-103 one sided P 042 httpwwwascopostcomNews58377
These outcomes suggest that although being very promising immunotherapy should be combined to other agents for being fully effective in gastric adenocarcinomas patients
We propose a strategy based on molecular features to select the drugs that will be associated with atezolizumab an anti-PDL1 drug in patients with pre-treated advanced gastric adenocarcinomas
Patients with tumors positive for EBV or microsatellite instable tumors 30 will be treated with atezolizumab and ipatasertib
Patients with genomically stable tumors 20 will be treated with atezolizumab combined with bevacizumab
Patients with tumors with chromosomal instability 50 will be treated with atezolizumab combined with bevacizumab
Expected outcomes
IMMUNOGAST trial will provide data about the clinical feasibility of biomolecular characterization of gastric adenocarcinomas for routine treatment adjustment Moreover it should generate information about the relevance of adjusting combined immunotherapies based on molecular subtypes in terms of clinical efficacy Finally translational research project outcomes should provide important data about relationships between efficacy and tumor immune gene spatial expression along with tumor and circulating mutational burden These outcomes may help identify the best candidates for tested combinations in the future
These numbers demonstrate the poor prognosis of this disease and the unmet medical need for innovative therapeutic strategies
Cancer Genome Atlas TCGA mapped a genomic landscape of gastric adenocarcinomas and identified 4 sub-types
Tumor positive for Epstein-Barr virus EBV 8 which display recurrent PIK3CA mutations extreme DNA hypermethylation and amplification of JAK2 ErbB2 PD-L1 and PD-L2
Microsatellite instable tumors MSI-high 22 which show elevated mutation rates including mutations of genes encoding targetable oncogenic signaling proteins PIK3CA ErbB2 ErbB3 and EGFR
Genomically stable tumors 20 which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins
Tumors with chromosomal instability 50 which show marked aneuploidy and focal amplification of receptor tyrosine kinases and VEGFA
Most of diffuse-type gastric adenocarcinomas were classified in genomically stable tumors This subgroup of cancers accounting for about 20 to 30 of gastric adenocarcinomas is associated with particularly poor prognosis and resistance to chemotherapy A proteomic landscape of diffuse-type gastric adenocarcinomas was recently reported
Pembrolizumab an anti-PDL1 drug granted with an accelerated approval by FDA in September 2017 exhibited promising activity in gastric adenocarcinoma patients previously treated with 1 or 2 lines of chemotherapy ORR116 median PFS 20 months median OS 56 months especially in those with PDL1 positive tumors ORR227 The tumor response was particularly high in patients with MSI-high tumor ORR571 However the preliminary outcomes of the phase III KEYNOTE-061 trial NCT02370498 recently released in the press suggest that pembrolizumab was not superior to paclitaxel in 592 patients with advanced gastric or gastroesophageal junction adenocarcinoma whose disease progressed after first-line treatment with platinum and fluoropyrimidine doublet therapy the hazard ratio HR for OS was 082 95 confidence interval 066-103 one sided P 042 httpwwwascopostcomNews58377
These outcomes suggest that although being very promising immunotherapy should be combined to other agents for being fully effective in gastric adenocarcinomas patients
We propose a strategy based on molecular features to select the drugs that will be associated with atezolizumab an anti-PDL1 drug in patients with pre-treated advanced gastric adenocarcinomas
Patients with tumors positive for EBV or microsatellite instable tumors 30 will be treated with atezolizumab and ipatasertib
Patients with genomically stable tumors 20 will be treated with atezolizumab combined with bevacizumab
Patients with tumors with chromosomal instability 50 will be treated with atezolizumab combined with bevacizumab
Expected outcomes
IMMUNOGAST trial will provide data about the clinical feasibility of biomolecular characterization of gastric adenocarcinomas for routine treatment adjustment Moreover it should generate information about the relevance of adjusting combined immunotherapies based on molecular subtypes in terms of clinical efficacy Finally translational research project outcomes should provide important data about relationships between efficacy and tumor immune gene spatial expression along with tumor and circulating mutational burden These outcomes may help identify the best candidates for tested combinations in the future
Detailed Description:
None
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2020-000297-17 | EUDRACT_NUMBER | None | None |