1623P - Pelareorep (pela) + atezolizumab (atezo) and chemotherapy in first-line (1L) advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) patients: Results from the GOBLET study

Background

Pela is an intravenously delivered unmodified oncolytic reovirus that selectively replicates in cancer cells and induces innate and adaptive immune responses. The GOBLET study assesses the safety and efficacy of pela in combination with atezo +/- chemotherapy in multiple gastrointestinal cancers. Here, we report clinical and translational results for the PDAC cohort.

Methods

GOBLET is a phase I/2 Simon 2-stage basket study. PDAC patients must have locally advanced and/or metastatic disease evaluable by RECIST and be eligible for 1L therapy. Patients received pela, atezo and gemcitabine/nab-paclitaxel. The first stage enrolled 13 evaluable patients (at least one post-baseline tumor assessment). Primary objectives are safety and efficacy (objective response rate [ORR]). The Stage 1 success criterion for PDAC is ≥3 confirmed responses. T cell receptor sequencing (TCR-seq) was performed on blood samples collected at baseline (cycle 1 day 1 [c1d1]), c2d1 and c4d1 to assess treatment effects on the T cell repertoire.

Results

No safety signals were observed in treated patients. Median age was 61 years; 92% had metastatic disease (69% liver). Eight of 13 evaluable patients had a partial response and 3 had stable disease for an ORR of 62% (confirmed ORR 53%) and a CBR of 85%. At the data cut-off (January 19, 2023), median duration of response was 6.0 month; 6-month progression-free survival (PFS) rate was 72.9% (95% CI 36.8-90.5), and 6-month overall survival (OS) rate was 82.1% (95% CI 44.4-95.3). Final PFS/OS are pending. TCR-seq revealed an expansion of new and preexisting T cell clones. Updated efficacy and TCR-seq results will be presented.

Conclusions

Pela combined with atezo and chemotherapy was well-tolerated. The ORR exceeded the pre-specified success criteria and compares favourably to ORRs from prior PDAC clinical trials in 1L PDAC. The changes in T cell repertoire observed by c2d1 are consistent with previous pela/checkpoint inhibitor studies and will be evaluated at later study timepoints.

Clinical trial identification

EudraCT 2020-003996-16.

Editorial acknowledgement

Legal entity responsible for the study

Oncolytics Biotech.

Funding

Oncolytics Biotech Inc.

Disclosure

D. Arnold: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi (Genzyme), Terumo, Boston Scientific, Amgen, Roche, Merck (Serono), Pierre Fabre Pharma, Servier, Ipsen, Boehringer Ingelheim, Eisai, GSK, Seagen, Viatris; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Sharp & Dohme, Terumo, Pierre Fabre Pharma, Boston Scientific, AstraZeneca, Gilead, Seagen, Janssen Cilag; Financial Interests, Personal, Invited Speaker, CME Provider: PRMA Consulting, Tactics MD LLC, WebMD Health Corp, From Research to Practice, Aptitude Health, art tempi media, Imedex, streamitup Germany, MedAhead (Austria), Clinical Care Options (CCO), mci; Financial Interests, Personal, Advisory Board, Consulting Agency: CRA International; Financial Interests, Personal, Advisory Board, CME Provider, App Producer: Onkowissen; Financial Interests, Personal, Other, Roles as Assoc. Editor for ESMO Open and Ann Oncol: Elsevier; Financial Interests, Personal, Other, Role as Associate Editor Clin Colorect Cancer: Elsevier; Financial Interests, Institutional, Other, DSMB chair: Sanofi (Genzyme); Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Pierre Fabre Pharma; Financial Interests, Institutional, Steering Committee Member: Roche; Financial Interests, Institutional, Coordinating PI: OncoLytics; Financial Interests, Institutional, Funding, Educational Grant: AbbVie; Non-Financial Interests, Project Lead: Oncolytics; Non-Financial Interests, Leadership Role, GI Group Steering Committee: EORTC; Non-Financial Interests, Leadership Role, Steering Committee Member: AIO (German Cancer Society); Non-Financial Interests, Member: ASCO, ESMO, DGHO. E. Goekkurt: Financial Interests, Institutional, Advisory Board: MSD, BMS, Daiichi; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, AstraZeneca, BMS, Novartis. A. Stein: Financial Interests, Institutional, Advisory Board: BMS, MSD, Amgen, Merck, Daiichi Sankyo, Roche, GSK, Servier, Taiho; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Writing Engagement: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: BMS, MSD, Servier, German Cancer Aid, Pierre Fabre, Merck; Financial Interests, Institutional, Steering Committee Member: Novartis; Non-Financial Interests, Member: DGHO, ASCO. U.M. Martens: Financial Interests, Personal, Invited Speaker: BMS, Roche; Financial Interests, Personal, Advisory Board: Guardant Health, Pierre Fabre, MSD; Financial Interests, Personal, Other, Travel support for congress: Janssen, Ipsen; Financial Interests, Personal, Full or part-time Employment, CEO: MOLIT Institute for personalized Medicine. J. Chater: Financial Interests, Institutional, Writing Engagement, Case Report: Lilly; Financial Interests, Institutional, Invited Speaker, Speaker Symposium Saxony Cancer Congress: AstraZeneca; Financial Interests, Institutional, Advisory Board: BMS, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Speaker in a Webinar: Lilly. H. Loghmani: Financial Interests, Personal, Full or part-time Employment: Oncolytics Bioteh Inc. M. Coffey: Financial Interests, Institutional, Full or part-time Employment, shareholder: Oncolytics Bioteh Inc.; Financial Interests, Personal, Full or part-time Employment: Oncolytics Biotech; Financial Interests, Personal, Other, Stocks/shares: Oncolytics Biotech; Non-Financial Interests, Leadership Role, President/CEO: Oncolytics Biotech. R. Trauger: Financial Interests, Institutional, Full or part-time Employment, Biotech: Oncolytics. T.C. Heineman: Financial Interests, Personal, Officer, Chief Medical Officer: Oncolytics Biotech; Financial Interests, Personal, Stocks/Shares: Oncolytics Biotech. All other authors have declared no conflicts of interest.