PO.CL05.13 · 临床研究
Pelareorep combined with atezolizumab and chemotherapy shows immune conversion activity in advanced pancreatic cancer: Biomarker results of cohort 1 of the GOBLET trial
作者与单位
摘要 Abstract
Introduction: Pancreatic cancer features a profoundly immunosuppressive microenvironment and no approved immunotherapy to date. Pelareorep (REOLYSIN®) is a wildtype oncolytic reovirus that preferentially replicates in RAS upregulated tumor cells. In cohort 1 of the phase 1/2 GOBLET trial, patients with advanced pancreatic cancer were enrolled to receive first line (1L) pelareorep combined with atezolizumab and gemcitabine/nab-paclitaxel yielding a previously reported confirmed objective response rate (ORR) of 54% (7/13) and disease control rate (DCR) of 85% (11/13).
Methods: In an exploratory biomarker analysis, routine serum markers (CA19-9, CEA, CRP) and 172 circulating proteins quantified via proximity extension assay (PEA; Olink®) were integrated with selected T cell receptor (TCR) sequencing and clinical outcomes. Linear mixed effects models and semi supervised clustering were applied to identify protein patterns reflecting immune and inflammatory activity.
Results: Early on-treatment effects included increased abundance of adaptive immune (e.g. IFN-gamma, CXCL11, TNF) or cytotoxicity associated proteins (e.g. GZMB/H/A) and reduced tumor/stroma-associated proteins (MUC-16, MMP12). A 14-protein signature linked to oncolytic activity (IFN gamma signaling, CD8+ and NK cytotoxic functions) stratified patients at week 4 into “hot” versus “cold” immune phenotypes relative to baseline. Despite small numbers, the ‘hot' phenotype was associated with significantly longer median progression free survival (n=6; mPFS; 7.5 mo, 95% CI: 7.1-14.3) compared with “cold” (n=6; mPFS 5.6 mo, 95% CI: 1.7-6.0; log rank p<0.005).
Conclusion: Pelareorep combined with atezolizumab and gemcitabine/nab-paclitaxel demonstrated promising activity in 1L pancreatic cancer. A hot/cold immune signature detectable after 4 weeks may serve as an early stratification biomarker, supporting identification of patients likely to achieve durable benefit
利益披露 Disclosure
H. Schürmann,
Servier Travel.
S. Liffers, None.
R. Trauger,
Oncolytics Biotech Employment.
T. Heineman,
Oncolytics Biotech Employment.
D. Arnold,
Amgen Independent Contractor.
AstraZeneca Independent Contractor, Travel, Other, Honoraria.
Boston Scientific Independent Contractor.
Bristol-Myers Squibb Independent Contractor, Other, Honoraria.
Daichii Sankyo Independent Contractor, Travel, Other, Honoraria.
GlaxoSmithKline Independent Contractor, Other, Honoararia.
Janssen Oncology Independent Contractor, Other, Honoraria.
Merck Serono Independent Contractor, Other, Honoraria.
Merck Sharp and Dome Independent Contractor, Other, Honoraria.
Sanofi/Regeneron Independent Contractor, Other, Honoraria.
Seagen Independent Contractor.
Pierre Fabre Independent Contractor.
Servier Independent Contractor, Other, Honoraria.
Takeda Independent Contractor, Other, Honoraria.
Terumo Other, Honoraria.
Oncolytics Biotech ).
J. T. Siveke,
FAPi Holding AG Stock, Other Business Ownership.
AstraZeneca Independent Contractor.
Bayer Independent Contractor.
Bristol-Myers Squibb Independent Contractor, ).
Roche Independent Contractor, ).
Abalos Therapeutics ).
Boehringer Ingelheim ).
Eisbach Bio ).
Servier Independent Contractor, Travel.
Falk Foundation Independent Contractor.
Immunocore Independent Contractor.
MCI Deutschland Independent Contractor.
MSD Independent Contractor.
Novartis Independent Contractor.
Oncolytics Biotech ).