Avetux (rituximab biosimilar) / Avesthagen - LARVOL DELTA

ICE study: Combination of irinotecan plus cetuximab and envafolimab as a rechallenge regimen in RAS/BRAF WT/MSS mCRC (ESMO-GI 2024) - P2 | "Patients have been treated in front lines with irinotecan and cetuximab and had a clinical benefit (complete or partial response) from both of them, no matter whether they had treated by any PD-1 inhibitor before.Any RAS WT/MSS mCRC patients who had got benefits from cetuximab or irinotecan will be treated with ICE regimen (Irinotecan 150mg/m2,Q2W, cetuximab 500mg/m2, Q2W, envafolimab 200mg, Q2w). The end point is PFS and the second end poing is OS and ORR."

Colorectal Cancer • BRAF • PD-L1

Efficacy and safety of combination regimen of irinotecan plus cetuximab and envafolimab (ICE regimen) in refractory RAS/BRAF WT/MSS mCRC (ESMO-GI 2024) - P2 | "This exploratory study of ICE regimen shows an inspiring clinical efficacy in refractory MSS/pMMR and RAS/BRAF wild-type mCRC pts. It seems to have longer PFS and OS than any other standard third-line treatment."

Clinical • Colon Cancer • Colorectal Cancer • Dermatology • BRAF

Avelumab (AVE), cetuximab (CET) and irinotecan (IRI) for treatment refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Characterization of the circulating immune response in the AVETUXIRI phase II trial (ESMO-GI 2024) - P2a | "Independently of RAS mutational status, modifications of TH17 and NKT cell frequencies in MSS mCRC patients' blood included in the AVETUXIRI trial seems to be associated with tumour response and patients' survival after treatment."

IO biomarker • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Avelumab (AVE), cetuximab (CET) and irinotecan (IRI) for treatment refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Translational analyses of the AVETUXIRI phase II trial (ESMO 2023) - P2a | "Table: 2237P Conclusions Independently of RAS mutation, existing adaptive immune response within metastases is associated with treatment benefit. ctDNA decrease is associated with tumor response."

IO biomarker • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • PD-1 • RAS

Avelumab (AVE) combined with cetuximab (CET) and irinotecan (IRI) for the treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): The AVETUXIRI phase II study (ESMO 2023) - P2a | "Conclusions Despite good tolerability, AVETUXIRI trial did not reach its efficacy endpoint. IS could be a predictive biomarker for selecting patients with potential treatment benefits."

Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • RAS

PJP Prophylaxis Needed with Steroids and Rituximab (RheumNow) - "Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening infection in immunocompromised patients. The 2023 EULAR Vasculitis guidelines recommends primary prophylaxis with antibiotics, especially in rheumatic disease patients receiving rituximab (RTX)....The benefit of primary PJP prophylaxis appears to be greatest in rheumatic patients receiving RTX and concomitant high-dose glucocorticoid treatment."

Online posting

[VIRTUAL] O07: INTERIM ANALYSIS OF THE AVETUXIRI TRIAL: AVELUMAB COMBINED WITH CETUXIMAB AND IRINOTECAN FOR TREATMENT OF REFRACTORY MICROSATELLITE STABLE (MSS) METASTATIC COLORECTAL CANCER (mCRC) – A PROOF OF CONCEPT, OPEN LABEL, NON-RANDOMIZED PHASE IIA STUDY. (mC (BWG 2021) - P2a | "Methods AVETUXIRI (NCT03608046) is a multicenter academic study recruiting MSS, BRAFV600E wt, mCRC patients (pts) refractory to standard treatment (fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR treatment if RAS wt tumor) in 2 cohorts (cohort A: RAS wt – cohort B: RAS mut)...Nevertheless, encouraging data of DCR, PFS and OS observed in RAS mut cohort allow the opening of a new cohort for RAS-mut mCRC (cohort C) with PFS as primary endpoint. A high-Immunoscore was associated with treatment benefit."

Clinical • IO biomarker • P2a data • Colorectal Cancer • Endocrine Disorders • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • CD8

2022 EULAR Recommendations for ANCA-associated Vasculitis (RheumNow) - "EULAR has published the 2022 update on recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)....For patients with AAV receiving rituximab, cyclophosphamide and/or high doses of glucocorticoids, we recommend the use of trimethoprim sulfamethoxazole as prophylaxis against Pneumocystis jirovecii pneumonia and other infections."

Online posting

Selection of PD-L1 escape variants in microsatellite stable metastatic colorectal cancer on avelumab treatment (ESMO 2022) - P2 | "The patient received 4 cycles of FOLFIRI/cetuximab, followed by 4 cycles FOLFIRI/cetuximab + avelumab, followed by avelumab maintenance treatment for 10 weeks until end of treatment (EOT) due to progression in week 19...Together with the emergence of truncated PD-L1 variants, regulation of PD-L1 availabilty but not epitope disruption appears to be the key mechanistic principle towards PD-L1 escape. Future trials confirming this principle in other entities are warranted especially in patient subpopulations with rs396991."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

Long-Term Benefit of Rituximab in Systemic Sclerosis (RheumNow) - "A small cohort trial of rituximab (RTX) in 29 systemic sclerosis patients showed significantly improved skin sclerosis and lung function after a follow-up of 96 weeks....This study showed the beneficial long term effects of RTX in a subset of SSc patients; and suggests that serum immunoglobulin levels should be explored as potential response biomarkers."

Online posting

Interim analysis of the phase II AVETUXIRI trial: Avelumab combined with cetuximab and irinotecan for treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). (ASCO 2022) - P2a | " AVETUXIRI trial (NCT03608046) enrols MSS, chemorefractory (fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR treatment if RAS wt tumor) mCRC patients in 2 cohorts (A: RAS-wt, n = 10 – B: RAS-mut, n = 13)... AVETUXIRI met its preliminary primary efficacy endpoint for RAS-wt mCRC pts, justifying its current continuation. Encouraging survival data observed in RAS-mut cohort allow the opening of a new cohort (PFS as primary endpoint). IS and adaptive immune response signature evaluated on metastases biopsies were associated with treatment efficacy and survival."

IO biomarker • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • CD8

Translational analysis and final efficacy of the AVETUX trial - Avelumab, cetuximab and FOLFOX in metastatic colorectal cancer. (PubMed, Front Oncol) - P2 | "In summary, we report the final overall survival of the AVETUX trial and propose T cell clonality and diversity as a potential marker to predict response to chemo-immunotherapy combinations in MSS mCRC by performing a central radiological review. ClinicalTrials.gov, identifier (NCT03174405)."

IO biomarker • Journal • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Microsatellite Instability • Oncology • Solid Tumor • BRAF • MSI

Rituximab Efficacy in Systemic Sclerosis (RheumNow) - "The DESIRES trial studied rituximab (RTX) in patients with systemic sclerosis (SSc) and showed clinically significant improvement in skin and lung outcomes after a subsequent 24-week open-label extension phase."

Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): Final results of the phase II AVETUX trial (AIO-KRK-0216). (ASCO-GI 2020) - P2; "The AVETUX regimen was feasible producing a high rate of responses in MSS pts mainly occurring within the first 8 weeks. The noted ORR/ETS of 79.5% warrants further evaluation in a randomized trial. Clinical trial information: NCT03174405."

Clinical • Combination therapy • IO Biomarker • P2 data • BRAF • KRAS • MSI • MSI-H • PD-L1

Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): Final results of the phase II AVETUX trial (AIO-KRK-0216). (ASCO-GI 2020) - P2; "The AVETUX regimen was feasible producing a high rate of responses in MSS pts mainly occurring within the first 8 weeks. The noted ORR/ETS of 79.5% warrants further evaluation in a randomized trial. Clinical trial information: NCT03174405."

Clinical • Combination therapy • IO Biomarker • P2 data • BRAF • KRAS • MSI • MSI-H • PD-L1

Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC) – Final Results of the phase II AVETUX trial (AIO-KRK-0216) (SITC 2019) - "The AVETUX regimen was feasible producing a high rate of responses in MSS pts mainly occurring within the first 8 weeks. The noted ORR/ETS of 79.5% warrants further evaluation in a randomized trial."

Clinical • Combination therapy • IO Biomarker • MSi-H Biomarker • P2 data • PD(L)-1 Biomarker • KRAS

Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): Results of the safety run-in phase of the phase II AVETUX trial (AIO-KRK-0216). (ASCO 2018) - P2; "The interim safety analysis has supported the feasibility of the AVETUX regimen in 1st line MCRC. The trial is ongoing."

Clinical • Combination therapy • P2 data • Colorectal Cancer

[VIRTUAL] Interim analysis of the AVETUXIRI Trial: Avelumab combined with cetuximab and irinotecan for treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC)—A proof of concept, open-label, nonrandomized phase IIa study. (ASCO-GI 2021) - P2a | " AVETUXIRI (NCT03608046) is a multicenter academic study recruiting MSS, BRAFV600E wt, mCRC patients (pts) refractory to standard treatment (fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR treatment if RAS wt tumor) in 2 cohorts (cohort A: RAS wt – cohort B: RAS mut)... The AVETUXIRI trial met its primary efficacy endpoint for RAS wt mCRC pts justifying the study continuation in cohort A (2nd stage). No PR was observed in RAS-mut cohort. Nevertheless, encouraging data of DCR, PFS and OS observed in RAS mut cohort allow the opening of a new cohort for RAS-mut mCRC (cohort C) with PFS as primary endpoint."

Clinical • IO biomarker • P2a data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

"Abstracts of interest for the #COLORECTAL community, related to #clinicaltrials, to be presented at #SITC2019 (Nov. 6-10): AVETUX, PolyPEPI1018, alloSHRINK, SHRINK, COM701 and more. #CRCSM" (@SassyCell)

Clinical