619P - Pelareorep + atezolizumab and chemotherapy in third-line (3L) metastatic colorectal cancer (mCRC) patients: Interim results from the GOBLET study

Background

Pelareorep (pela) is an intravenously administered, non-genetically modified oncolytic reovirus that selectively kills tumor cells and activates innate and adaptive immune responses. Pela primes tumors for checkpoint inhibition by enhancing tumor infiltrating lymphocytes and PD-L1 expression. The GOBLET study is assessing safety and efficacy of pela + atezolizumab (atezo) +/- chemotherapy in multiple gastrointestinal cancers. Here we report the interim results for 3L mCRC with microsatellite stable (MSS) disease.

Methods

GOBLET is a phase 1/2 Simon two-stage basket study. Eligible patients must have mCRC failing 2 prior lines of chemotherapy. Patients receive pela, atezo and trifluridine/tipiracil. The first stage enrolled 15 evaluable patients (patients with at least one post-baseline tumor assessment). Primary objectives are safety and efficacy (per tumor response/disease stabilization). The Stage 1 success criterion for 3L CRC is ≥4 patients with stable disease at Week 16. Blood samples were collected for T cell receptor sequencing (TCR-seq) to assess treatment effects on the T cell repertoire.

Results

No safety signals were observed in treated patients. Five of 15 evaluable patients had stable disease (SD) as their best response, including 4 with SD at week 16. 10 patients had progressive disease (PD). The overall clinical benefit rate was 33%. Translational research, including TCR-seq, supported findings: an expansion of new and preexisting T-cell clones was demonstrated. Updated efficacy (PFS and OS) and TCR-seq results will be presented.

Conclusions

Consistent with previous clinical trials of pela, the investigational combination therapy was well-tolerated. The primary efficacy success criterion was met. Given pela’s immunologic mechanism of action and the significant changes seen in the T cell repertoire by C2D1, we hypothesize that potentially protective immune responses may have been initiated. However, these heavily pretreated patients may have been too immunocompromised or have insufficient time before progressing to benefit fully from the immunotherapy.

Clinical trial identification

EudraCT 2020-003996-16.

Editorial acknowledgement

Legal entity responsible for the study

Oncolytics Biotech Inc.

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, Institutional, Invited Speaker: Pierre Fabre Pharma, Bristol Myers Squibb, Roche, OncoLytics; Financial Interests, Personal, Other, Role as Associate Editor Clin Colorect Cancer: Elsevier; Financial Interests, Institutional, Other, DSMB chair: Sanofi (Genzyme); 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, ESO, DGHO. E. Goekkurt: Financial Interests, Institutional, Advisory Board: MSD, Bristol Myers Squibb, Daiichi Sankyo; Financial Interests, Institutional, Local PI: msd, Daiichi Sankyo AstraZeneca, Bristol Myers Squibb, Novartis. A. Stein: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, 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: Bristol Myers Squibb, MSD, Servier, German Cancer Aid, Pierre Fabre, Merck; Financial Interests, Institutional, Steering Committee Member: Novartis; Non-Financial Interests, Member: DGHO, ASCO. 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: Bristol Myers Squibb, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Speaker in a Webinar: Lilly. U.M. Martens: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, 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. 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.