CompletedPhase 2

Personalized Targeted IMMUNOtherapy-based Regimens in Recurrent GASTric Adenocarcinoma (IMMUNOGAST)

France54 participantsStarted 2021-03-19

Plain-language summary

For patients with advanced/metastatic 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) = 2.9 months; median overall survival (OS)= 5.9 months), or paclitaxel alone (ORR = 14%, median PFS = 2.9 months; median OS= 5.9 months); 2) docetaxel (ORR = 7%, median OS = 5.2 months) or 3) irinotecan (ORR = 0%, median OS= 4.0 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 (ORR=11.6%, median PFS = 2.0 months, median OS= 5.6 months), especially in those with PDL1 positive tumors (ORR=22.7%). The tumor response was particularly high in patients with MSI-high tumor (ORR=57.1%). 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 0.82 (95% confidence interval = 0.66-1.03; one sided P = .042) (http://www.ascopost.com/News/58377). 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.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Histologically and/or cytologically documented recurrent advanced/metastatic gastric or gastroesophageal junction adenocarcinomas\* previously treated with a platinum and fluoropyrimidine-based regimen. \* The gastric or gastroesophageal junction adenocarcinomas that overexpress HER2 should have previously been treated with trastuzumab, except in the case of contraindication. * Patients older than 18 years * Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 * Patients must have documented disease progression * Patients who have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Accessible tumor lesion (primitive lesion or metastasis) for trial dedicated tumor biopsy. * Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (echo) or multigated acquisition (MUGA) scan within 28 days before day 1 of treatment. * Child-Pugh class A * Patients must have normal organ and marrow function: * Absolute neutrophil count ≥ 1,500/μL, platelets ≥ 100,000/μL, hemoglobin ≥ 9 g/dL * Total bilirubin ≤ 1.5 ULN except subject with documented Gilbert's syndrome, AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN, Serum alkaline phosphatase ≤ 2.5 x ULN. Patients with bone metastases: alkaline phosphatase ≤ 5 x ULN. * Albumin \> 2.5 mg/dL. * Glomerular filtration rate ≥ 60 mL/min as determined by the CKD-EPI equation (or reference methodology such as Iohexol or isotopic technic). * Uri…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Objective response rate

Timeframe: Through the expected duration of the treatment, an average of 27 weeks and a maximum of 2 years (estimated)

Trial details

NCT IDNCT04739202

SponsorHospices Civils de Lyon

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-06-04

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