DSMB Approves Continued GOBLET Cohort 5 Enrollment in Pancreatic Cancer

Microscopic image of pancreatic cancer cells - Generated with Google Gemini AI

Continuation of enrollment in cohort 5 of the phase 1/2 GOBLET study has been recommended by the Data Safety Monitoring Board (DSMB) following a review of initial safety data.¹

GOBLET is a randomized, open-label, multicenter study that utilizes a Simon two-stage design to evaluate treatments across multiple gastrointestinal cancers. The study aims to assess the efficacy and safety of pelareorep (Reolysin), an oncolytic reovirus, in various cohorts.

In cohort 5, researchers are specifically investigating pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX; fluorouracil [5FU], irinotecan, and oxaliplatin), with or without the PD-L1 inhibitor atezolizumab (Tecentriq), in patients with newly diagnosed pancreatic ductal adenocarcinoma (PDAC).

"We see a promising opportunity for pelareorep to improve treatment options for [patients with] PDAC," said Thomas Heineman, MD, PhD, chief medical officer at Oncolytics, in a press release. "The current standard of care is primarily chemotherapy, such as gemcitabine plus nab-paclitaxel or mFOLFIRINOX. Pelareorep has already shown synergy with gemcitabine, nab-paclitaxel, and atezolizumab in GOBLET cohort 1, and demonstrating efficacy with mFOLFIRINOX would further establish its potential to benefit [patients with] PDAC.”

Full updates from the trial are expected in 2025, and safety data are anticipated to be released in the first half of the year. Initial efficacy results are planned to follow in the second half.

“This study also builds on cohort 1 by evaluating pelareorep's ability to work with checkpoint inhibitors, which would be a major advance, especially as immune therapies provide little benefit in most patients with this 'cold' tumor," added Heineman.

Study Design and Cohort 5 Objectives

The GOBLET study is being conducted at 17 centers in Germany and managed by AIO-Studien-gGmbH. Further, it spans multiple gastrointestinal cancer indications and comprises 5 cohorts:

1. Pelareorep plus atezolizumab (Tecentriq), gemcitabine, and nab-paclitaxel for first-line advanced/metastatic pancreatic cancer.
2. Pelareorep plus atezolizumab for first-line microsatellite instability-high metastatic colorectal cancer.
3. Pelareorep plus atezolizumab and TAS-102 for third-line metastatic colorectal cancer.
4. Pelareorep plus atezolizumab for second-line advanced and unresectable anal cancer.
5. Pelareorep plus mFOLFIRINOX with/without atezolizumab for newly diagnosed metastatic PDAC.

Cohorts demonstrating efficacy in stage 1 may progress to stage 2 to expand patient enrollment and advance clinical validation.

In the mFOLFIRINOX cohort within the GOBLET study, a 3-patient safety run-in phase is being used to evaluate the tolerability of 2 treatment arms. The first is studying pelareorep with mFOLFIRINOX and atezolizumab, and the second is pelareorep plus mFOLFIRINOX. Following the safety run-in, a total of 15 evaluable patients will be randomly assigned to each arm in stage 1.

The study’s coprimary end points are objective response rate assessed at week 16 and safety. The secondary end points of the trial include additional efficacy assessments and evaluation of potential biomarkers, such as T-cell clonality and CEACAM6.² If pre-specified criteria are met, 1 or both arms may advance to stage 2, which will enroll an additional 17 patients per arm.

References:

1. Oncolytics Biotech® reports completion of initial safety phase enrollment for GOBLET trial's new pancreatic cancer cohort. News release. Oncolytics Biotech® Inc. December 3, 2024. Accessed December 3, 2024. https://tinyurl.com/y93uw55e

2. Oncolytics Biotech® reports interim results from phase 1/2 GOBLET study showing a 70% objective response rate in pancreatic cancer at the SITC Annual Meeting. News release. Oncolytics Biotech® Inc. November 7, 2022. Accessed December 3, 2024. https://tinyurl.com/3ttdmbzp