Advancing Cancer Treatment: Clinical Trials in Oncolytic Virus Therapy
By: Ayesha Rashid, PhD
Interviewee: Thomas C. Heineman, MD, PhD, Chief Medical Officer, Oncolytics Biotech
Advancing Cancer Treatment: Clinical Trials in Oncolytic Virus Therapy
By: Ayesha Rashid, PhD
Interviewee: Thomas C. Heineman, MD, PhD, Chief Medical Officer, Oncolytics Biotech
The oncology clinical trial landscape has seen dramatic shifts in recent years, driven by advancements in precision medicine, immunotherapies and targeted treatments.
Advancements in clinical trial methodologies, including artificial intelligence (AI)-driven patient recruitment, decentralized trials and biomarker-driven study designs, are changing the way cancer therapies are developed.
While some of these elements have made clinical trials more efficient, they also introduce new challenges in recruitment, regulatory approval and data interpretation.
Patient recruitment remains one of the biggest hurdles in oncology trials. Many patients do not qualify due to stringent eligibility criteria, and others may be hesitant to participate due to concerns about receiving placebos instead of active treatments.
AI-driven models can help identify optimal patient populations, predict treatment responses and streamline trial operations.
Thomas Heineman, MD, chief medical officer at Oncolytics Biotech, told Xtalks that operational challenges like finding the right patients and identifying the best sites for studies can be optimized using AI and big data approaches. “This has the potential to make clinical trials more efficient,” he says.
Oncolytics Biotech is currently conducting clinical trials for its lead candidate — an oncolytic virus therapy called pelareorep — in difficult-to-treat cancers such as metastatic breast cancer and pancreatic cancer.
The company is evaluating the therapy in HR-positive, HER2-negative breast cancer, the most common genetic subtype, accounting for approximately 70% of all breast cancer cases. For patients with early HR-positive, HER2-negative breast cancer that is inoperable or has metastasized, several treatment options are available. However, over time, these treatments tend to lose effectiveness, leaving patients with limited alternatives.
The Promise of Oncolytic Viruses in Cancer Treatment
Oncolytic viruses can be genetically engineered or naturally occurring viruses designed to selectively infect and destroy cancer cells either directly or, more commonly, by stimulating anti-tumor immune responses. As such, they are considered a type of immunotherapy.
Dr. Heineman describes how the field of oncolytic viruses has evolved significantly over the years, which includes a better understanding of their mechanism of action.
Data from clinical trial samples have provided valuable insights into the mechanism of action of Oncolytics Biotech’s lead candidate, pelareorep.
While it exhibits multiple effects, its primary therapeutic impact can be summarized by two key complementary actions, explains Dr. Heineman. First, it stimulates anti-tumor immune responses and second, it enhances tumor recognition by the immune system.
When administered to a patient, pelareorep stimulates the expansion and activation of cellular immune responses that target the tumor, such as tumor-infiltrating lymphocytes (TILs), which are specifically primed to recognize and attack the cancer cells directly.
Alongside this, by triggering a cascade of cytokines and other signaling molecules within the tumor, it modifies the tumor microenvironment, making it more accessible to immune cells. This allows tumor-targeting immune cells to infiltrate and effectively attack the cancer.
“Originally, we thought that the main mechanism of action would be that we would give it to patients, and it would just get in and kill the tumor,” Dr. Heineman explains. “It later became very clear that while it does do that to a degree, what it’s really doing primarily is stimulating immune responses that can then come in and attack the tumor.”
This dual action — direct tumor cell destruction and immune system activation — makes oncolytic viruses particularly compelling as cancer therapeutics.
Oncolytics Biotech’s pelareorep can be administered intravenously, allowing it to circulate through the bloodstream and reach tumors throughout the body. This makes it more practical and potentially more effective compared to other oncolytic viruses that require direct injection into tumors.
Dr. Heineman says there’s also a lot of potential for oncolytic viruses to partner with immunotherapies to extend their usefulness.
“Metastatic pancreatic cancer is a terrible disease with very limited long-term survival rates. The treatment landscape has not changed dramatically over many years now. There’s obviously a very strong need in pancreatic cancer to discover and make available to patients better treatment options.”
— Thomas C. Heineman, MD, PhD, Chief Medical Officer, Oncolytics Biotech
“Metastatic pancreatic cancer is a terrible disease with very limited long-term survival rates. The treatment landscape has not changed dramatically over many years now. There’s obviously a very strong need in pancreatic cancer to discover and make available to patients better treatment options.”
— Thomas C. Heineman, MD, PhD, Chief Medical Officer, Oncolytics Biotech
Key Findings from Clinical Trials
Oncolytics Biotech has been conducting a series of clinical trials to assess the efficacy and safety of pelareorep in combination with other therapies. The results so far have been promising.
In a randomized Phase II study in HR-positive, HER2-negative metastatic breast cancer, patients who received the combination of pelareorep and paclitaxel (a standard chemotherapy drug) showed nearly double the median overall survival compared to those who received paclitaxel alone.
The patients who received the combination therapy had a median overall survival of 21 months compared to 10.8 months in patients who received the standard-of-care chemotherapy alone.
A follow-up study, the BRACELET-1 trial, further validated these findings. Patients receiving pelareorep plus paclitaxel experienced a near-doubling of median progression-free survival, from 6.4 months to over 12.1 months, with profound improvements in two-year survival rates.
Oncolytics Biotech is looking to advance into a larger randomized, potentially licensure-enabling study of approximately 180 patients.
Similarly, in pancreatic cancer, a recent cohort from the Phase I/II GOBLET study demonstrated tumor responses in 62% of patients treated with pelareorep in combination with chemotherapy, and a checkpoint inhibitor, a result that Dr. Heineman describes as “very compelling,” given that it far exceeds historical response rates in this challenging disease.
“Metastatic pancreatic cancer is a terrible disease with very limited long-term survival rates. The treatment landscape has not changed dramatically over many years now. There’s obviously a very strong need in pancreatic cancer to discover and make available to patients better treatment options,” he says.
The ability of pelareorep to significantly improve response rates in combination with existing therapies is indeed encouraging in this indication.
Oncology Clinical Trials: Considerations, Trends and Paths Forward
Conducting clinical trials in oncology presents significant challenges, as patients require timely and effective treatments.
Placebo-based studies are rarely feasible, as withholding treatment is not an ethical option. Therefore, careful consideration must be given to selecting an appropriate comparator in any trial. This means determining what patients in the control group will receive, ensuring that it aligns not only with the study’s scientific objectives but also with the best interests of the patients, explains Dr. Heineman.
The selected control must be a relevant standard of care that provides meaningful treatment while allowing for a rigorous evaluation of the investigational therapy’s efficacy.
Additionally, for a therapy to be effective in real-world settings, it must be both tolerable and safe for patients. Even those with advanced diseases, such as pancreatic and breast cancer, often remain functional and actively engaged in their daily lives.
Therefore, clinical trials must be designed in a way that allows patients to continue living as normally as possible while minimizing adverse reactions or side effects that could further impact their well-being, says Dr. Heineman. The goal is to develop treatments that not only extend survival but also maintain or improve the quality of life for those undergoing therapy.
Another important consideration is for clinical trials to be carefully balanced in size — large enough to generate meaningful data, yet not so extensive that they expose patients to unnecessary risks with investigational treatments before their safety and efficacy are fully established, explains Dr. Heineman.
Additionally, the oncology landscape is constantly evolving, and lengthy trials run the risk of becoming outdated before they conclude, potentially requiring a reassessment of the study approach. Despite these challenges, innovative strategies continue to improve the efficiency of clinical trials, making promising therapies available faster.
“We think there’s a lot of potential, we’re not coming close to running out of ideas or work to do. We’ve got a lot on our plates that we want to move forward.”
— Thomas C. Heineman, MD, PhD, Chief Medical Officer, Oncolytics Biotech
“We think there’s a lot of potential, we’re not coming close to running out of ideas or work to do. We’ve got a lot on our plates that we want to move forward.”
— Thomas C. Heineman, MD, PhD, Chief Medical Officer, Oncolytics Biotech
Regulatory Considerations and Approval Pathways
The success of Oncolytics Biotech’s pelareorep in early-stage trials underscores the importance of well-designed clinical studies in bringing innovative therapies to patients. As Oncolytics Biotech moves towards larger Phase II/III trials, regulatory considerations play a significant role.
“If we see efficacy results anywhere close to what we saw in the BRACELET-1 study, that would be highly statistically significant and could form a strong foundation for a potential license application through the FDA’s accelerated approval pathway,” Dr. Heineman notes.
Regulatory agencies like the FDA are adapting to the evolving landscape of oncology drug development. The accelerated approval pathway provides a faster route for promising therapies to reach the market while maintaining stringent safety and efficacy standards.
Speeding up the development process is beneficial not just from a business perspective, but more importantly for patients, as it helps bring novel, effective treatments to them sooner.
“The FDA has become increasingly sensitive to the need to advance the development of new therapies in cancer and other areas as quickly and efficiently as possible,” Dr. Heineman states. “They have worked on their own processes for making that happen, while retaining their very high standards to make sure that the drugs that get approved are effective and safe.”
Partnerships and Collaborations in Drug Development
The development of novel, innovative therapies is complex and can often benefit from collaboration between industry, academia and regulatory bodies. Oncolytics Biotech has forged key partnerships to support its R&D efforts.
Oncolytics Biotech has a number of ongoing collaborations with both academic institutions and industry partners who help explore pelareorep’s potential in different indications.
These collaborations have been instrumental in expanding the understanding of the drug’s mechanism of action. In some cases, academic researchers have even led their own clinical trials using pelareorep, further demonstrating its potential across various cancers, including pancreatic and breast cancer, explains Dr. Heineman.
He also says the company continues to engage with independent investigators who bring unique ideas, hypotheses and approaches to the field.
In addition to academic partnerships, Oncolytics Biotech has also formed clinical collaboration agreements with major pharmaceutical companies. For example, the BRACELET-1 study, which demonstrated meaningful clinical benefits, was conducted in collaboration with Pfizer, which was “very supportive,” says Dr. Heineman.
Furthermore, because pelareorep is often studied in combination with other therapies — such as checkpoint inhibitors — the company also has supply agreements with other companies, like Roche, to facilitate these studies.
These collaborations are not only standard in the industry but also mutually beneficial, accelerating the development of innovative treatments while supporting broader scientific advancements in oncology.
Future Pathways for Oncolytic Virus Therapy
With a strong clinical foundation and promising data, Oncolytics Biotech is advancing pelareorep into late-stage trials. The company is also exploring its potential for earlier-stage cancers, as well as in combination with CAR-T cell therapies for hard-to-treat solid tumors.
Dr. Heineman says, “We think there’s a lot of potential, we’re not coming close to running out of ideas or work to do. We’ve got a lot on our plates that we want to move forward.”
As the field of oncolytic viruses continues to grow, robust oncology clinical trials remain central to unlocking their potential and bringing novel cancer treatments to patients.
ABOUT Thomas C. Heineman
Prior to joining Oncolytics, Dr. Thomas Heineman was Senior Vice President and Head of Clinical Development at Denovo Biopharma. Before joining Denovo, he served as Vice President and Head of Clinical Development at both Genocea Biosciences and Halozyme Therapeutics. At Halozyme, Dr. Heineman was also Head of Translational Medicine and oversaw clinical trials in indications such as breast and pancreatic cancer.
Dr. Heineman’s experience further extends to big pharma and academia, as he previously worked as Senior Director, Global Clinical Research and Development at GlaxoSmithKline and as an Associate Professor at the Saint Louis University School of Medicine.
Dr. Heineman has co-authored over 60 peer-reviewed publications and is board certified in Internal Medicine and Infectious Diseases. He completed his fellowship in Infectious Diseases at the National Institutes of Health and his internship and residency at the University of Maryland. Dr. Heineman earned his MD and PhD in Virology at the University of Chicago.