Neoadjuvant Pembrolizumab with a Watch-and-wait Strategy for Patients with Mismatch Repair-deficient or Microsatellite Instability-high (dMMR/MSI-H) Localized Colon Cancer: a Randomized GERCOR G-109 PRODIGE 84 PREMICES Phase II Trial

The goal of this investigational study is to evaluate neoadjuvant pembrolizumab with a watch-and-wait approach for localized dMMR/MSI-H CRC patients. The PREMICES trial is based on the hypothesis that non-operative management is efficient for dMMR/MSI-H localized CRC patients treated with neoadjuvant pembrolizumab.
Eligible patients will be randomized to receive pembrolizumab with a watch-and-wait approach (experimental arm) or standard strategy (surgical resection ±adjuvant chemotherapy; control arm) in a 1:1 ratio.

开始日期2024-12-01

申办/合作机构

Groupe Coopérateur Multidisciplinaire en Oncologie

[+1]

NCT06275737 / RecruitingN/AIIT

Trimodal Peri Operative Prehabilitation for Upper Oesogastric and Pancreatic Cancer: A Multicenter, Two-cohort, Open-label, Single-arm POP-UP GERCOR Study

This is a multicenter, two-cohort, open-label, single-arm feasibility study. The primary objective is to assess the feasibility of the 8-week trimodal prehabilitation program alongside perioperative triplet chemotherapy in eligible patients with localized pancreatic ductal adenocarcinoma (PDAC) or oesogastric cancer (OGC) .

开始日期2024-08-01

申办/合作机构

Groupe Coopérateur Multidisciplinaire en Oncologie

NCT06253611 / Recruiting临床2期IIT

Gut Microbiome Intervention With EXL01 in Combination With Nivolumab and FOLFOX as First-line Treatment for Patients With PD-L1 CPS ≥5 Metastatic Gastric Cancer: A Randomized GERCOR Phase II Study (BIG)

This is a randomized non-comparative, multicenter phase II study in patients with PD-L1 PD-L1 combined positive score (CPS) ≥5 advanced gastric cancer to evaluate the efficacy and safety of nivolumab and FOLFOX in combination with EXL01 as first-line treatment.
After signing the informed consent form, and upon confirmation of the patient's eligibility, patients will be randomized in a 2:1 ratio to either the nivolumab and FOLFOX plus EXL01 arm (experimental) or the nivolumab and FOLFOX arm (control). In both arms, treatment will be given until PD, unacceptable toxicity or for a maximum of 24 months (52 cycles).

开始日期2024-07-01

申办/合作机构

Groupe Coopérateur Multidisciplinaire en Oncologie

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项与 Groupe Coopérateur Multidisciplinaire en Oncologie 相关的文献（医药）

2023-08-01·Annals of oncology : official journal of the European Society for Medical Oncology

Prediction of response to immune checkpoint blockade in patients with metastatic colorectal cancer with microsatellite instability

Article

作者: Despras, E ; Ratovomanana, T ; Duval, A ; Renaud, F ; André, T ; Cros, J ; Labrèche, K ; Buhard, O ; Colle, R ; Siret, A ; Touat, M ; Benusiglio, P ; Cohen, R ; Guillerm, E ; Bennouna, J ; Le Rouzic, P ; de Reynies, A ; Alentorn, A ; Tournigand, C ; Tougeron, D ; Fléjou, J-F ; Coulet, F ; Nicolle, R ; Collura, A ; Letourneur, Q ; Svrcek, M ; Ayadi, M ; Fouchardière, C de la ; Jonchère, V ; Bourgoin, P ; Diehl, A ; Cervera, P ; Prunier, C ; Perrier, A

BACKGROUND:

Mismatch repair-deficient (dMMR) tumors displaying microsatellite instability (MSI) represent a paradigm for the success of immune checkpoint inhibitor (ICI)-based immunotherapy, particularly in patients with metastatic colorectal cancer (mCRC). However, a proportion of patients with dMMR/MSI mCRC exhibit resistance to ICI. Identification of tools predicting MSI mCRC patient response to ICI is required for the design of future strategies further improving this therapy.

PATIENTS AND METHODS:

We combined high-throughput DNA and RNA sequencing of tumors from 116 patients with MSI mCRC treated with anti-programmed cell death protein 1 ± anti-cytotoxic T-lymphocyte-associated protein 4 of the NIPICOL phase II trial (C1, NCT03350126, discovery set) and the ImmunoMSI prospective cohort (C2, validation set). The DNA/RNA predictors whose status was significantly associated with ICI status of response in C1 were subsequently validated in C2. Primary endpoint was progression-free survival by immune RECIST (iRECIST) (iPFS).

RESULTS:

Analyses showed no impact of previously suggested DNA/RNA indicators of resistance to ICI, e.g. MSIsensor score, tumor mutational burden, or specific cellular and molecular tumoral contingents. By contrast, iPFS under ICI was shown in C1 and C2 to depend both on a multiplex MSI signature involving the mutations of 19 microsatellites hazard ratio cohort C2 (HR_C2) = 3.63; 95% confidence interval (CI) 1.65-7.99; P = 1.4 × 10^-3] and the expression of a set of 182 RNA markers with a non-epithelial transforming growth factor beta (TGFB)-related desmoplastic orientation (HR_C2 = 1.75; 95% CI 1.03-2.98; P = 0.035). Both DNA and RNA signatures were independently predictive of iPFS.

CONCLUSIONS:

iPFS in patients with MSI mCRC can be predicted by simply analyzing the mutational status of DNA microsatellite-containing genes in epithelial tumor cells together with non-epithelial TGFB-related desmoplastic RNA markers.

2020-12-01·BMC cancer2区 · 医学

Atezolizumab plus modified docetaxel-cisplatin-5-fluorouracil (mDCF) regimen versus mDCF in patients with metastatic or unresectable locally advanced recurrent anal squamous cell carcinoma: a randomized, non-comparative phase II SCARCE GERCOR trial

2区 · 医学

ArticleOA

作者: Desramé, Jérôme ; Buecher, Bruno ; Jary, Marine ; Parzy, Aurélie ; Tougeron, David ; Samalin, Emmanuelle ; Ghiringhelli, François ; François, Éric ; Dahan, Laëtitia ; Baba-Hamed, Nabil ; Rebucci-Peixoto, Magali ; Bidard, François-Clément ; Jacquin, Marion ; André, Thierry ; Kim, Stefano ; Vendrely, Véronique ; Spehner, Laurie ; Borg, Christophe ; Vernerey, Dewi ; Taieb, Julien ; de la Fouchardière, Christelle ; El Hajbi, Farid ; Bouché, Olivier ; Smith, Denis

Abstract:

Background:

Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) regimen has become a new standard for the treatment of metastatic or unresectable locally advanced recurrent squamous cell carcinoma of the anus (SCCA) after demonstrating improved efficacy (12-month PFS of 47%) in the Epitopes-HPV02 trial. Antibodies targeting the checkpoint inhibitor (CKI) programmed cell death protein-1 (PD1) have demonstrated the efficacy as monotherapies in second-line treatment of SCCA. The aim of this study is to evaluate the combination of atezolizumab and mDCF as first-line chemotherapy in a non-comparative multicentre randomized phase II study of advanced SCCA patients.

Methods:

Patients with chemo-naive advanced histologically proven SCCA, metastatic or unresectable locally advanced recurrence, and Eastern Cooperative Oncology Group-performance status (ECOG-PS) < 2 will be eligible. The primary endpoint is a 12-month PFS rate. Using one-arm non-parametric survival with unilateral alpha type I error of 5% and a statistical power of 80%, the upper critical value for the 12-month PFS rate is 47% to reject H0. Assuming 5% lost to follow-up, 99 patients will be randomized on a 2:1 basis, 66 to the experimental arm (arm A, mDCF plus atezolizumab) and 33 to the standard arm (arm B, mDCF). In both arms, 8 cycles of mDCF will be administered. In arm A, patients receive mDCF with a fixed dose of atezolizumab (800 mg every 2 weeks) and are followed up to 1 year. Secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and an extensive biomarker programme and its correlation with the treatment efficacy.

Discussion:

Although the Epitopes-HPV02 trial has changed long-lasting prognosis of patients with SCCA in advanced stage disease, more than 50% of patients will progress at 12 months. The purpose of the SCARCE trial to establish the addition of atezolizumab to mDCF as a new standard in this rare disease. Associated biomarker studies and the control arm could contribute to better understanding of the potential synergic and tumour resistance mechanisms in SCCA.

Trial registration:

NCT03519295.

2018-05-20·Journal of clinical oncology : official journal of the American Society of Clinical Oncology1区 · 医学

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial

1区 · 医学

Article

作者: Egreteau, Joëlle ; de Gramont, Aimery ; Faroux, Roger ; Ychou, Marc ; Fratte, Serge ; Mabro, May ; Louvet, Christophe ; Taieb, Julien ; Khalil, Ahmed ; Lepere, Céline ; Dauba, Jérôme ; André, Thierry ; Ghiringhelli, François ; Mineur, Laurent ; Deplanque, Gaël ; Bonnetain, Franck ; Dourthe, Louis Marie ; Vernerey, Dewi ; Bez, Jeremie ; Becouarn, Yves ; Hug de Larauze, Marine ; Bouche, Olivier ; Bennouna, Jaafar ; Desrame, Jérôme ; Chibaudel, Benoist ; Dupuis, Olivier ; Paget-Bailly, Sophie ; Bachet, Jean-Baptiste ; Galais, Marie Pierre

Purpose:

Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers.

Methods:

In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive.

Results:

A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49).

Conclusion:

IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

项与 Groupe Coopérateur Multidisciplinaire en Oncologie 相关的新闻（医药）

2022-05-12

·GlobeNewswire

OSE Immunotherapeutics To Present at ‘Immuno-Oncology Summit Europe’ and at ‘Tumor Myeloid-Directed Therapies Summit’ In London and Boston

NANTES, France, May 11, 2022 (GLOBE NEWSWIRE) -- OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) has been invited to provide an update on its R&D programs in immuno-oncology at two dedicated international conferences in May and June. The Company’s broad presence in scientific cancer research events confirms its expertise in the highly attractive field of myeloid cells and macrophages, identified as poor prognostic factors in oncology and in immune escape mechanisms of cancer immunotherapies. Details of the OSE Immunotherapeutics presentations: Immuno-Oncology Summit Europe 2022 May 23-25, London, UK, and Online Date and time of presentation: Monday, May 23rd at 11:00 Myeloid Checkpoints: Validated and Novel Targets from Target Validation to Clinical Translation Tumor Myeloid-Directed Therapies Summit June 14-16, Boston, MA Date and time of presentation: Wednesday, June 15th at 10:00am ET Modulating Myeloid Cell Functionality via the SIRPa-CD47 axis and Novel CLEC1 Checkpoints to Bridge the Adaptive and Innate Immune Systems The presentations will focus on: * CLEC-1, a novel checkpoint to regulate the antigen cross-presentation properties of dendritic cells; The identification and validation of novel immune checkpoint targets and development of their antagonists as an innovation in cancer immunotherapy to enhance myeloid cells and promote antigen presentation to bridge the innate and adaptative immune system; How the SIRPα-CD47 axis stimulates macrophages to recruit the adaptive immune arm via chemoattraction, and inhibition of this pathway may avoid T cell exclusion in synergy with T cell immune checkpoint and clinical translation. *Collaborative program between OSE Immunotherapeutics and Dr Elise Chiffoleau’s (https://cr2ti.univ-nantes.fr/research/team-1) research teams (Center for Research in Transplantation and Translational Immunology (CR2TI), UMR1064, INSERM, Nantes University at Nantes University Hospital). ABOUT OSE Immunotherapeutics OSE Immunotherapeutics is an integrated biotechnology company focused on developing and partnering therapies to control the immune system for Immuno-Oncology and Immuno-Inflammation. Its balanced first-in-class clinical and preclinical portfolio has a diversified risk profile: Immuno-Oncology first-in-class products Tedopi ® (innovative neoepitope combination): the Company’s most advanced product; positive results for Phase 3 trial (Atalante 1) in Non-Small Cell Lung Cancer patients in secondary resistance after checkpoint inhibitor failure. Other ongoing combination trials sponsored by cooperative clinical research groups in oncology: Phase 2 in pancreatic cancer (TEDOPaM), sponsor GERCOR. Phase 2 in ovary cancer, in combination with pembrolizumab (TEDOVA), sponsor ARCAGY-GINECO. Phase 2 in non-small cell lung cancer in combination with nivolumab, sponsor Italian foundation FoRT. BI 765063 (OSE-172, anti-SIRPα mAb on CD47/SIRPα pathway): developed in partnership with Boehringer Ingelheim in advanced solid tumors; positive Phase 1 dose escalation results of BI 765063 in monotherapy and in combination with ezabenlimab (PD-1 antagonist); ongoing expansion Phase 1. OSE-279 , anti-PD1 – advanced preclinical stage. BiCKI®: bispecific fusion protein platform built on the key backbone component of anti-PD1 combined with a new immunotherapy target (for example: BiCKI®-IL7, preclinical stage) to increase anti-tumor efficacy. Immuno-Inflammation first-in-class products OSE-127/S95011 (humanized monoclonal antibody antagonist of IL-7 receptor): developed in partnership with Servier; positive Phase 1 results; ongoing Phase 2 in ulcerative colitis (sponsor OSE) and ongoing Phase 2a in Sjögren’s syndrome (sponsor Servier). FR104 (anti-CD28 monoclonal antibody): licensing partnership agreement with Veloxis Pharmaceuticals, Inc. in transplantation; ongoing Phase 1/2 in renal transplant (sponsored by the Nantes University Hospital); US IND obtained by Veloxis Pharmaceuticals, Inc. for a clinical trial; Phase 2 planned in an autoimmune disease indication. OSE-230 (ChemR23 agonist mAb): preclinical stage therapeutic agent with the potential to resolve chronic inflammation by driving affected tissues to tissue integrity. CoVepiT: a prophylactic second-generation vaccine activating cytotoxic T lymphocytes against COVID-19, developed using optimized epitopes from SARS-CoV2 viral proteins, epitopes non impacted by multi-variants. Shows good tolerance and very good level of T cell immune response. In clinical testing, a long-term memory response was confirmed at 6 months.

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