Breakthrough Clinical Results
Oncolytics Biotech announced positive clinical and translational data for pelareorep in metastatic colorectal cancer (mCRC). In the REO 022 trial, pelareorep combined with FOLFIRI and bevacizumab showed a median progression-free survival (PFS) of 16.6 months and a median overall survival (OS) of 27.0 months in KRAS mutant patients, significantly exceeding the standard of care. The GOBLET study also showed positive results in a 3L mCRC setting. Translational data confirmed pelareorep's mechanism of action, involving viral replication and immune activation within tumors. Oncolytics plans to discuss regulatory pathways and advance towards a registration-enabled study in KRAS mutant mCRC patients.
Key Highlights
- Pelareorep demonstrated significantly improved PFS and OS compared to standard of care in KRAS mutant mCRC patients in the REO 022 trial.
- Positive results were also observed in the GOBLET study's 3L mCRC cohort.
- Translational data confirmed pelareorep's mechanism of action, including viral replication and immune activation.
- Oncolytics plans to pursue a registration-enabled study in KRAS mutant mCRC patients.
Incidence and Prevalence
Latest Global Estimates of Metastatic Colorectal Cancer
Colorectal cancer is among the most prevalent and lethal cancers globally, with a significant portion presenting as metastatic disease. According to recent data, nearly one-quarter of colorectal cancer cases present with de novo metastatic disease (stage IV) at diagnosis.
A 2025 systematic review of 84 eligible studies from 46 countries covering 3.8 million patients found that the most recent distant metastatic CRC proportions varied from 16.2% in Puerto Rico to 28.2% in Oman and Latvia, with a median of 23.7% (interquartile range, 21.8%-26.3%).
Over a 10-year period (2010-2020), 43,054 de novo metastatic CRC cases were identified in the Surveillance, Epidemiology, and End Results database. The liver was the most common metastatic site, accounting for 80% of cases.
Demographic and regional variations are significant: - Higher metastatic proportions were observed in younger patients, those with colon cancer, and in regions without screening implementation - No apparent difference was found between males and females in global metastatic proportions - Countries with higher Human Development Index (HDI) and Socio-Demographic Index (SDI) correlated with lower proportions of distant metastatic CRC (HDI: ρ = -0.48; SDI: ρ = -0.26)
Temporal trends vary by region: - Some countries showed declining proportions of metastatic CRC (e.g., Southern Portugal decreased from 36.5% in 2000 to 22.2% in 2016) - Others remained stable (e.g., Austria, Belgium) - Some regions showed increasing proportions (e.g., United States, Slovenia, Spain)
Racial and ethnic disparities are evident: - Colorectal cancer mortality rates are significantly greater in African American than in European American individuals, and this disparity is worsening - Non-Hispanic Black patients had higher odds of synchronous lung and liver metastases compared to non-Hispanic White patients across all age groups - Early-onset American Indian/Alaska Native patients were over twice as likely to present with lung metastases (OR: 2.10, 95% CI 1.11-3.98) compared to non-Hispanic White patients - A 2023 study analyzing CT images from 1584 metastatic colorectal cancer patients found that Africans and Caucasians had more advanced disease at baseline
Prognosis remains poor, with less than 20% survival five years after diagnosis of metastatic CRC, and most patients with metastatic disease cannot be surgically treated.
These findings highlight the global burden of metastatic colorectal cancer and underscore the importance of early detection strategies, particularly in regions with limited screening programs and among high-risk populations.
Study Design Parameters
Study Design Parameters and Endpoints in Key mCRC Trials
Trial Designs and Parameters
Randomized controlled trials (RCTs) have been fundamental in evaluating treatments for metastatic colorectal cancer (mCRC). A systematic review identified 150 phase III clinical trials with 77,494 total enrollments for mCRC patients. These trials have assessed various aspects including the impact of primary tumor location (differentiating between right-sided and left-sided colorectal cancers) and the effectiveness of biological therapy.
The RECOURSE trial examined prognostic factors by dividing patients into subgroups with good prognostic characteristics (<3 metastatic sites and ≥18 months from diagnosis) and poor prognostic characteristics. The CAIRO2-trial, a multicenter phase III study, evaluated first-line capecitabine, oxaliplatin and bevacizumab (CAPOX-B), with or without cetuximab.
A Delphi survey among 30 international experts identified essential baseline characteristics for phase 3 trials, including age, performance status, primary tumor location, primary tumor resection, prior chemotherapy, number of metastatic sites, liver-only disease, and mutation status. The most relevant stratification factors were: RAS/BRAF mutation status, performance status, primary tumor sidedness, and liver-only disease.
Endpoints in mCRC Trials
Overall survival (OS) was the primary endpoint in many trials, with 45.5% of these trials meeting their predefined endpoint. Progression-free survival (PFS) is commonly used as a surrogate endpoint for OS and was the primary endpoint in several studies including the CAIRO2-trial and a phase II trial evaluating famitinib.
Other important endpoints include: - Objective response rate (ORR) assessed through Response Evaluation Criteria in Solid Tumors - Disease control rate (DCR) - Early tumor shrinkage (ETS) - Resection rate - Quality of life (QoL), recognized as particularly important for later-line therapy
Trial Outcomes and Significance
Although 46.6% of trials met their predefined primary endpoint, only 26.5% resulted in improvement in overall survival by ≥2 months. Median OS in trials has increased significantly over time, from 12 months (1986-1996) to 21 months (2007-2015), but 5-year OS remained low at 12.2% in 2011.
The CORRECT and CONCUR phase III trials demonstrated that regorafenib improved overall survival in heavily pretreated patients with treatment-refractory mCRC. The SUNLIGHT trial evaluated FTD/TPI (trifluridine/tipiracil) plus bevacizumab in third-line mCRC and met all recommended thresholds for clinically meaningful improvements.
Challenges in conducting RCTs in advanced mCRC include funding, ethical approval processes, equipoise, patient preferences, logistical issues, disease progression, and palliative care. Notably, third-line therapies or later (odds ratio, 0.57) and pharmaceutical company funding (odds ratio, 0.57) were less often associated with improvement in OS.
Pelareorep Clinical Trials Beyond Metastatic Colorectal Cancer
Based on the available information, there is limited data regarding pelareorep being investigated for indications other than metastatic colorectal carcinoma.
A 2023 meta-analysis indicates that pelareorep is an oncolytic virus that causes oncolytic effects in many solid tumors and has shown therapeutic benefits. This meta-analysis specifically compared pelareorep combined with chemotherapy to traditional chemotherapy alone in patients with advanced solid tumors.
The meta-analysis included five studies involving 492 patients with advanced solid tumors. However, the specific types of solid tumors beyond metastatic colorectal cancer were not explicitly identified in the available information.
Regarding the efficacy outcomes, the meta-analysis concluded that the addition of pelareorep to traditional chemotherapy did not lead to significant improvements in: - Overall Survival (OS) - Progression-Free Survival (PFS) - Objective Response Rate (ORR)
in patients with advanced solid tumors.
The available information does not specify any other oncological indications or non-oncological indications for which pelareorep is being investigated. Similarly, there are no details provided about specific intervention models or trial designs for studies involving pelareorep beyond its use in combination with chemotherapy for advanced solid tumors.
While pelareorep appears to have potential applications across multiple solid tumor types due to its oncolytic properties, the specific cancer types and detailed intervention protocols are not outlined in the provided information.