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The September issue of ONCOLOGY features a rare case study on glioblastoma, discussions on end-of-life care, and insights into the field of pediatric oncology. 

September ONCOLOGY Publication

In a conversation with CancerNetwork®, Yun Rose Li, MD, PhD, assistant professor and physician-scientist from the Department of Radiation Oncology at City of Hope, detailed the clinical catalyst behind the phase 2 IMPACT-ADT trial (NCT07202247). The study was born from a striking observation during Li’s prior research on intermittent fasting: a patient with no traditional cardiac risk factors experienced a ST-elevation myocardial infarction (STEMI) weeks after initiating androgen deprivation therapy (ADT). This event underscored a critical gap in oncologic care—the difficulty clinicians face when using existing criteria to predict which patients will develop acute cardiovascular events of testosterone suppression.

She further explained that as patients with prostate cancer live longer, the competing risk of cardiovascular morbidity moves to the forefront of clinical decision-making. Standard ADT, which is known to induce metabolic shifts—including insulin resistance, increased visceral adiposity, and sarcopenic obesity—may result in acute coronary events occurring within the first 6 months of therapy, often before significant, visible changes in body composition or muscle mass take place. To address these risks, the IMPACT-ADT trial—a collaboration with cardio-oncologist June-Wha Rhee, MD, funded by the American Heart Association—will evaluate 3 protective strategies: intermittent fasting, glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide (Ozempic) or tirzepatide (Mounjaro), and the American Heart Association’s “Life’s Essential 8” guidelines.

According to Li, the decision to study GLP-1 agonists was driven by their increasing prevalence in standard medical practice and their established benefits in reducing cardiovascular disease. Although some concerns exist regarding muscle wasting, Li emphasized that the trial’s short-term focus prioritizes immediate cardiac protection during the high-risk initial phase of ADT. Furthermore, the study utilizes a multidisciplinary team, including board-certified endocrinologists, to monitor for gastrointestinal (GI) adverse effects (AEs). Although these symptoms can overlap with radiation-induced toxicities, early data suggest that GLP-1 agents are well-tolerated alongside definitive radiotherapy. Ultimately, the IMPACT-ADT trial seeks to provide an evidence-based framework to mitigate treatment-related risks and optimize long-term survivorship.

CancerNetwork: What was the background behind conducting the phase 2 IMPACT-ADT trial?

This was initially inspired by my own patients from a prior study. What I am referring to is our phase 2 randomized study looking at intermittent fasting in patients undergoing pelvic radiotherapy. In that study, we were looking at the role of fasting vs nutritional counseling to mitigate radiation toxicity. While I was conducting that study, one of the earliest patients I enrolled on the study developed a full classical STEMI, and it happened a few weeks into him starting hormonal therapy. He had none of the major risk factors of someone whom we would expect to have a heart attack.

When that happened, it [prompted] me to think: “What are the long-term and short-term consequences of hormonal therapy?” Because of that patient, I started to look and follow other patients who were getting hormonal therapy. Even though I am a radiation oncologist, I trained at an institution where we are the ones prescribing hormonal therapy. This was an issue near and dear to my heart.

As patients are living longer and being diagnosed later with prostate cancer, competing risk in terms of morbidity and mortality becomes an ever more important issue at the forefront of how we think of clinicians. There are patients whom we think probably need hormone therapy, but we might be shortening their lifespan or causing significant harm to their overall quality of life. We must weigh this; should we do hormone therapy or not?

To make that informed decision, we need to know who’s going to be at risk. It’s easy to identify patients who are “clearly at risk”: they had a prior heart attack, they had prior stents placed, [or] they have a history of stroke. The patients who have no prior cardiac history may not even have diabetes and may not even be significantly morbidly obese. Those are the ones where we don’t know who is going to be at risk. That was one of the patients whom I initially met for my other study, and that made me think about how we can start to address these issues and identify risk factors.

That’s what prompted the development of the study and the strong collaboration with my [co-principal investigator], June-Wha Rhee, MD, who is a cardio-oncologist at City of Hope. She and I are both physician scientists, and her research team is interested in ADT’s native effects on the heart and the cardiovascular system as well as being able to model those risk factors. When I started to run my study and see multiple patients come in with coronary artery disease and related risk factors plus those who did not have risk factors but then developed coronary artery disease, it prompted me to [think], “What are the risks in patients who are bearing that?” We don’t know. We’re not able to adequately inform them. That’s what motivated us to write this study.

Given the metabolic profile of patients on ADT, specifically regarding the risk of sarcopenic obesity, what was the rationale for choosing a GLP-1 agonist over other agents?

It was a question raised by the American Heart Association. Rhee and I wrote a grant that’s now funded by the American Heart Association. It was part of their Translational Collaborative Sciences Award (CTSA) program, specifically aiming to bring together clinicians across different disciplines to think about important questions to address in cardiovascular disease.

The reviewers brought up this question, too, [regarding] the concern about muscle wasting as a risk factor related to GLPs. Part of the reason we chose GLP as [treatment for] one of the arms of the study was fundamentally because more patients, regardless of whether we had the study or not, were coming in asking to be on the drug or be placed on the drug as a part of standard of care. We realized we had no information on the long-term or even short-term safety of putting patients on this agent. It was an important question to study, and it was almost chosen for us because of this new wave of interest in GLP agents. There has been a lot of data looking at GLP and reducing cardiovascular disease in patients with obesity and diabetes as prior risk factors. We thought that this would be a reasonable drug to study, as patients are already coming in and receiving them. Part of the rationale for the study was to look at patients getting short-term hormone therapy. We debated this back and forth to consider whether we should focus on short-term [therapy alone] or short-term and long-term hormone therapy.

To take a step back, patients with prostate cancer are recommended 6 months or longer [in] terms of hormone therapy, depending on how aggressive their prostate cancer is and their [phase of] disease. In different contexts, different durations of hormone therapy are recommended.

The reason we chose to focus on 6 months of hormone therapy is because, interestingly enough, the vast majority of patients who experience an acute coronary event are getting these events within the first 6 months, which is counterintuitive to how we think about the negative impact of ADT. We know ADT has negative effects on muscle mass [and] on visceral obesity. We know that it has effects on insulin resistance and glucose control, as well as circulating lipid profiles. All these things are negatively affected by testosterone suppression. It’s an overall systemic protection for men in terms of all these metabolic risk factors. If that’s true, then one would guess that the risk of cardiac events will continue to increase over time if patients are getting, say, 2 years [of therapy]. Then, why are all the events happening in the first 6 months?

Fundamentally, we are not that worried about how much muscle loss is happening in that initial phase. If I have a patient getting, say, 2 years of hormone therapy, it wouldn’t surprise me if, at 6 months into their hormonal treatment, I don’t observe substantial weight gain, muscle loss, or increase in adiposity. Interestingly, in such patients, it’s not uncommon that after the first 6 months, when their testosterone is recovering at 9 or 12 months, you start to see some of those things because their testosterone is still not fully recovered and they are technically suppressed.

[Regardless of what] is causing this increased cardiac risk, there is some disconnect between our understanding of what ADT does to the metabolism and what it also does to the cardiac system. There may be a discrepancy in terms of what’s putting patients at risk in terms of short-term coronary events and long-term coronary artery events; we strongly encourage patients to do resistance-based exercise. Strength training and resistance training are important for maintaining bone density as well.

Are there other specific AEs that you are monitoring more closely in patients undergoing concurrent radiation therapy?

GLP has its own risks related especially to the GI system, and radiation can sometimes cause GI-related toxicities. We have a closer eye on those kinds of things, whether that’s nausea or changes in bowel habits and loose stools. However, all patients [assigned] to the GLP arm are meeting routinely with a board-certified endocrinologist who specializes in managing GLP. That’s why we don’t necessarily need to monitor them so closely during radiation.

From a radiation standpoint, I don’t expect a whole lot more in terms of toxicity, partly because nausea is quite rare in terms of radiation-related [adverse] effects for prostate cancer; it happens in less than 5% to 10% of the patients we see, on average. More [often] than not, GLP tends to slow down bowel function; during radiation, we see more things like diarrhea and loose stools. They’re probably counteracting each other, if we were to guess. We haven’t seen anything so far in terms of patients I’ve treated; I’ve treated probably a dozen patients on GLP before, during, or after radiation as part of their standard of care. They’re getting GLP from their primary [provider] or from their endocrinologist, and those patients have not experienced [unexpected] toxicities.

Metabolic interventions (time-restricted eating, GLP1 Receptor Agonist, and heart healthy diet) to improve cardiometabolic health in prostate cancer patients during androgen deprivation therapy, IMPACT-ADT trial. ClinicalTrials.gov. Updated February 4, 2026. Accessed February 5, 2026. https://tinyurl.com/juvxzzbu

Articles

Based on the prevalence of GLP-1 agonists employed in standard medical practice, Li’s team will assess their impact on radiotherapy for prostate cancer.

Exploring The Impact of ADTs on Cardiac Risk in Prostate Cancer Treatment

Loaiza-Bonilla anticipates that AI-assisted EKG models could be cleared for use in risk stratification for receipt of surgery or drug use.

Examining EKGs in Foundational Models for Cardio-Oncology

In a conversation with CancerNetwork®, Arturo Loaiza-Bonilla, MD, MSEd, FACP, the systemwide chief of Hematology and Oncology at Saint Luke’s University, discussed the application of electrocardiograms (EKGs) in foundational models to help facilitate cardio-oncology processes.

First, he highlighted the importance of foundational models, which could include millions of tests that are generalizable to specific use cases. Regarding EKGs, he suggested that tests could be used to detect cardiovascular abnormalities and emerging adverse effects with certain agents, especially for patients with cardiovascular comorbidities.

Loaiza-Bonilla further explained that due to the ubiquity of EKGs, the FDA would likely afford clearances to their use in foundational models to risk-stratify patients for surgery or drug use. He concluded by stating that the integration of EKG models into electronic medical records (EMRs), in addition to other data-driven algorithms, would help “move the needle” in terms of delivering better care.

[These topics] are about foundational models. Foundational models mean very large data sets that include hundreds or hundreds of thousands, sometimes millions, of tests, all labeled and being built for [generalizability] to a specific use case. In this case, it could be the detection of arrhythmias or risk factors such as QT prolongation in patients taking [tyrosine kinase inhibitors] or [adverse] effects that are emerging, particularly for patients who may have predispositions such as cardiovascular disease.

The use of EKGs in foundational models is becoming a new trend. There are several companies doing so at this moment, trying to show the FDA the validity of those tests and those foundational models. What I anticipate is, because these EKGs are so easy to use now—they’re ubiquitous—we hopefully can help to do some clearances for either potential surgeries the patients may have, or if they are on treatment, predicting the risk of having complications from the drugs that we use. It’s a combination of the EKG models plus other algorithms that are more data-driven in terms of integration with the EMR, which are going to be helpful to really move the needle. More to follow on that; we are going to probably be hearing more in the next year or so.

Analyzing Theranostics in Radiation Oncology at the 2026 ACRO Summit

2026 Annual American College of Radiation Oncologists (ACRO) Summit

, experts in radiation oncology across a multitude of disease states gathered to discuss the hottest and latest topics in the field. Among them, CancerNetwork® spoke with Brandon Mancini, MD, MBA, FACRO, about the importance of theranostics in the wake of a discussion he delivered titled, “Theranostics in radiation oncology: Building programs, empowering teams, shaping the future”.

Theranostics, by definition, is a personalized medical approach that combines targeted therapy with diagnostic molecular imaging. Mancini, the medical director for BAMF Health, as well as the editor at large for the RadOnc Review and host of the 

 podcast, stated that it is currently advancing in radiation oncology, and that the platform of ACRO provides a voice to help expand it even further.

On top of focusing on what theranostics is, the discussion touched upon the data that has led to many FDA approvals across many disease states, including the important role radiation oncology has to play with regards to theranostics. He ended by stating that, hopefully, the talk would serve as a call to action to motivate more radiation oncologists to use theranostics daily in their own practice.

Why is theranostics an important topic in radiation oncology right now?

Theranostics in general is this escalating field within radiation oncology, nuclear medicine, and oncology and beyond. This is a neat opportunity, with ACRO being one of the salient meetings in radiation oncology to continue the conversation, get more in depth to theranostics, and to excite or motivate people to consider this as part of their practice each and every day.

What are some of the key takeaways from your discussion on theranostics at ACRO?

It’s going to be reviewing exactly what theranostics is, for those who may not be aware, reviewing the data that has led to the FDA approval of the agents we use each and every day, reviewing why radiation oncology plays an important role within this space, and a call to action to motivate people to be interested, involved, and consider incorporating this into their cancer care every day.

Videos

Theranostics is an escalating field within radiation oncology and clinicians should be utilizing it every day, according to Brandon Mancini, MD, MBA, FACRO.

J. Isabelle Choi, MD, outlined evidence-based strategies for radiation dose escalation in locoregionally advanced breast cancer.

, J. Isabelle Choi, MD, presented a comprehensive overview of strategies to improve outcomes in locoregionally advanced or recurrent breast cancer.

 As advances in early detection and multimodality therapy improve overall survival, clinicians are increasingly encountering the challenge of managing isolated locoregional recurrences (iLRR) and high-risk nodal involvement. Choi’s presentation offered actionable guidance for radiation oncologists on dose escalation for internal mammary nodes (IMN) and supraclavicular (SCV) nodes, as well as technical and clinical considerations for safe breast reirradiation. Here are the top 5 takeaways for radiation oncologists based on her presentation.

Choi is an associate attending radiation oncologist at Memorial Sloane Kettering Cancer Center.

1. Implement Selective Boosting for Clinically Involved Nodal Basins

For patients with locoregionally advanced disease, undissected and clinically involved nodal basins—specifically the IMN and supraclavicular SCV fossa—should receive a radiation boost during adjuvant therapy.

Complete Response (CR) to Neoadjuvant Chemotherapy:

 A 10 Gy boost is recommended for patients who achieve a radiographic or clinical CR.

 For residual disease after neoadjuvant chemotherapy, the boost dose should be escalated to 14 Gy to 20 Gy.

 Data from MD Anderson show that implementing these boosts (10 Gy for CR; 16 Gy for residual disease) resulted in a 5-year local-regional recurrence-free survival of 89%, with only approximately 2% IMN failures.

2. Delineate Nodal Targets Using Pre-Treatment Imaging

Precise treatment planning requires the localization and delineation of involved nodes using all available clinical data, including pre-neoadjuvant chemotherapy CT, MRI, and PET scans.

 Coverage should include the involved interspace plus 1 interspace above and below. Standard coverage typically involves the first 3 intercostal spaces, but more inferior coverage up to the 5th interspace is necessary if lower nodes were involved.

3. Prioritize Comprehensive Fields for High-Risk Recurrences

When treating breast cancer recurrence, particularly in the chest wall (CW) or regional lymph nodes, a comprehensive treatment approach is more favorable rather than limited "involved field" reirradiation.

 This approach typically includes the breast or chest wall plus the regional lymph nodes.

 Recurrences are often treatment-refractory and associated with high-risk features like lymphovascular invasion or dermal lymphatic invasion.

 MSK data on comprehensive photon reirradiation showed a local recurrence rate of 5.6%, a regional recurrence rate of 8.9%, a distant recurrence rate of 27.0%, and overall survival rate of 82% at a median follow-up of 63 months.

4. Respect Cumulative Dose Constraints for Critical Organs

Reirradiation is a high-risk procedure where cumulative doses often exceed standard constraints. Clinicians must meticulously track dose-volume histograms (DVH) from both treatment courses.

 The cumulative maximum dose should ideally be kept below 75 Gy to 85 Gy to minimize the risk of plexopathy.

 Strong consideration should be given to highly conformal techniques, such as IMRT/VMAT or proton therapy, to spare the heart and lungs.

 Patients must be counseled on risks such as rib fractures (late grade 2 events were observed in approximately 6.1% of MSK photon cases), chest wall pain, and reconstruction failure in patients with implants.

5. Adopt an Individualized, Multidisciplinary Approach

There is currently a lack of standardization in reirradiation, making individualized treatment plans essential.

 Use caution if the interval between radiation courses is less than 1 year.

 Management should include a discussion of maximal surgical resection and systemic therapy alongside radiation.

For limited in-breast recurrence, repeat breast cancer therapy should be considered.

For high in-breast recurrence, CW/isolated lymph node recurrence should be considered.

: Clinicians should be prepared to manage and follow acute long-term toxicities. These may include long-term skin care, daily massages, or vitamin E.

Choi I. Improving outcomes in locoregionally advanced or recurrent breast cancer. Presented at ACRO 2026 Radiation Oncology Summit, Orlando, FL; February 5, 2026.

Andring LM, Diao K, Sun S, et al. Locoregional management and prognostic factors in breast cancer with ipsilateral internal mammary and axillary lymph node involvement. 

. 2022;113(3):552-560. doi:10.1016/j.ijrobp.2022.02.037

Chakraborty MA, White C, Zhang Z, et al. 1082 - Curative-intent photon reirradiation for local-regional breast cancer recurrence. 

2025;123(1):S214. doi:10.1016/j.ijrobp.2025.07.1320

Maximizing Control Via Radiation in High-Risk and Recurrent Breast Cancer

Five patients experienced grade 2 to 4 acute graft-versus-host disease (GVHD), with grade 2 events occurring in 2 patients, 1 patient, and 1 patient at dose levels 1, 3, and 4, respectively, as well as 1 patient in dose level 3 experiencing a grade 4 acute GVHD event.

Treatment with TRX103, an allogenic Tr1 cell product, exhibited manageable safety and dose-dependent exposure, expansion, and persistence in a small cohort of patients with hematologic malignancies undergoing HLA-mismatched hematopoietic cell transplantation (HCT), according to findings from a presentation given at the 

Specifically, among 12 patients who underwent TRX103 infusion, no dose-limiting toxicities (DLTs) were observed by day 28 of treatment. Moreover, no serious adverse effects (SAEs) were observed related to TRX103 infusion in this population, with 2 patients experiencing a grade 1 infusion reaction and transient rash, respectively. Hematopoietic stem cell transplantation (HSCT) engraftment was initiated in all patients, with a median time to neutrophil engraftment of 17 days (range, 14-31) and 100% donor chimerism at a median of 32 days (range, 28-36).

Moreover, 5 patients experienced grade 2 to 4 acute graft-versus-host disease (GVHD), with grade 2 events occurring in 2 patients, 1 patient, and 1 patient at dose levels 1, 3, and 4, respectively, as well as 1 patient in dose level 3 experiencing a grade 4 acute GVHD event. Regarding severity, 2 patients experienced mild chronic GVHD at dose levels 1 and 3, 1 patient experienced moderate chronic GVHD at dose level 3, and 1 patient experienced severe chronic GVHD at dose level 1.

Preliminary clinical data revealed that complications due to underlying disease were the most prominent at the lowest dose levels. A total of 3 patients experienced disease relapse, including 2 patients with acute myeloid leukemia (AML) in the first and second dose levels, respectively, at day +120 and +210. One patient treated at dose level 4 with B-cell acute lymphoblastic leukemia (B-ALL) experienced a relapse at day +85. Additionally, 1 death was observed at day +72 due to respiratory failure, but it was deemed unattributable to TRX103.

“[There was] no DLT at day 28 after using the [TRX] cells. Engraftment was confirmed in all patients with no issue,” Monzr Al Malki, MD, director of the Unrelated Donor Bone Marrow Transplant and Haploidentical Transplant Programs and associate professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, said in his presentation of the study data. “No SAEs related to the cells themselves [were observed]. There was one [infusion-related reaction] at the [225 x 10

Patients selected for enrollment on the study had B- or T-cell ALL, AML, myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML). They were also undergoing HLA-mismatched related or unrelated hematopoietic peripheral blood stem cell transplantation (PBSCT).

Screening occurred 35 to 8 days before study treatment, wherein cohort dose level assignments for TRX were determined. Patients underwent conditioning on days –7 to –1, and HSCT infusion was given on day 0 of study treatment. GVHD prophylaxis was provided on days 3 and 4 of study treatment, TRX103 was infused on day 6 of study treatment, and a DLT evaluation window was conducted from day 6 to 34 of study treatment.

In addition, patients received mycophenolate mofetil (MMF) or sirolimus (Rapamune). Sirolimus was given starting on day 5 of study treatment at a loading dose of 4 to 6 mg, followed by 1 to 2 mg daily, which tapered from day 60 to 90 and was discontinued between days 100 and 150. MMF was initiated day 5 at a dose of 3 g or less daily, with patients discontinuing the agent between days 28 and 35 of study treatment.

The study followed a modified 3+3+3 design, and the respective dose levels in each cohort for the escalation portion of the trial were 25 x 10

 DRX cells. Patients in the expansion cohort will be treated at recommended dose levels determined by a safety review committee (SRC) evaluation.

The trial included 1 patient with CMML, 3 with MDS, 4 with B-ALL, and 4 with AML. Two patients received myeloablative conditioning, and 10 received reduced-intensity conditioning. The median age at the time of PBSCT was 66 years (range, 37-73).

Moreover, there was a total of 8 haploidentical and 4 HLA-mismatched unrelated donor transplants in this patient group. The median number of infused CD34-positive cells was 5.02 x 10

 cells/kg (range, 4.05-8.06), and the median nucleated cell total was 4.84 x 10

The primary end points of the trial were the safety and tolerability of TRX103. Secondary end points included incidence of grade 2 to 4 acute GVHD, incidence and severity of chronic GVHD, and 1-year overall survival. Exploratory objectives included pharmacokinetics and pharmacodynamics, time to immune reconstitution, and incidence of 1-year GVHD-free relapse-free survival.

Disclosures: Al Malki disclosed having received research funding from Miltenyi Biotec, Orca Bio, Stemline Therapeutics, Takada, and Incyte; serving in advisory committees for Hasna Biopharma, Gilead, Gamida Cell, and Incyte; and serving in a consultancy role for Tscan, TrX1 Inc., Ossium Health, Cellkure, MaaT, and CareDx.

Al Malki MM, Juckett M, Perales MA, et al. Off-the-shelf engineered Tr1 cells (TRX103) in patients with hematological malignancies undergoing HLA-mismatched hematopoietic cell transplantation (HCT) show safety and dose dependent effects. Presented at: 2026 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 4-7, 2026; Salt Lake City, UT. Abstract 8

No serious adverse effects were observed with TRX103 in patients with hematologic malignancies undergoing HLA-mismatched HCT.

Off-the-Shelf TRX103 Exhibits Early Tolerability in Select HCT Populations

Supporting data for the designation came from the phase 1 REO 022 trial (NCT01274624) evaluating the novel therapeutic combination among those with KRAS-mutant metastatic CRC.

Pelareorep (Reolysin) in combination with bevacizumab (Avastin) and leucovorin, fluorouracil, and irinotecan (FOLFIRI) has earned fast track designation from the FDA as a treatment for patients with microsatellite stable (MSS) metastatic colorectal cancer (CRC) harboring 

mutations, according to a press release from the developer, Oncolytics Biotech® Inc.

Supporting data for the designation came from the 

 evaluating the novel therapeutic combination among those with 

-mutant metastatic CRC. Previous findings showed that the pelareorep combination yielded an overall response rate (ORR) of 33%, which exceeded a historical rate of 10% with standard-of-care therapy in this population.

According to additional findings from the REO 022 trial, the median progression-free survival (PFS) was 16.6 months with pelareorep-based therapy vs 5.7 months with standard second-line therapy.

 Furthermore, the median overall survival (OS) was 27.0 months with the experimental regimen and 11.2 months with standard second-line treatment.

“This designation is an important validation of our focus on pelareorep’s potential as a platform immunotherapy for gastrointestinal cancers like [CRC]. Adding pelareorep to the standard of care in this underserved segment of [patients with CRC] results in a doubling or tripling of critical clinical endpoints, including [OS], [PFS], and [ORR],” Jared Kelly, chief executive officer at Oncolytics, stated in the press release.

 “Pelareorep offers the potential to help a meaningful number of patients, and I look forward to continuing to collaborate with the FDA to address this treatment gap as expeditiously as possible.”

Developers designed pelareorep as a naturally occurring non-enveloped human reovirus.

 According to the investigators of the REO 022 trial, the specificity of the reovirus for targeting RAS-transformed cells and its relatively nonpathogenic nature in humans may make it a viable anti-cancer therapy candidate.

In the dose-escalation phase 1 study, 36 patients were assigned to receive pelareorep as a 1-hour intravenous infusion on days 1, 2, 3, 4, and 5 every 4 weeks. Investigators also administered irinotecan as a 90-minute intravenous infusion on day 1 every 2 weeks at dose levels ranging from 125 to 180 mg/m

, leucovorin as a 2-hour infusion at 400 mg/m

 on day 1 every 2 weeks, fluorouracil at 400 mg/m

 as a continuous intravenous infusion over 46 hours on day 1 every 2 weeks, and bevacizumab at 5 mg/kg on day 1 every 2 weeks.

The trial’s primary end points included dose-limiting toxicities and pharmacokinetic parameters. Secondary end points included ORR, PFS, OS, clinical benefit rate, and safety and tolerability.

Patients 18 years and older with histologically confirmed cancers of the colon or rectum with radiologically documented and measurable metastases, no prior receipt of FOLFIRI or irinotecan in the metastatic setting, and 

-mutated disease were eligible for enrollment on the trial. Other eligibility criteria included having no lasting acute toxicities related to any prior radiotherapy, an ECOG performance status of 0 to 2, and a life expectancy of at least 3 months.

Those with brain metastases; known HIV infection or active hepatitis B or C; receipt of more than 20 Gy of radiation to the pelvis; or receipt of chemotherapy, immunotherapy, hormonal therapy, or major surgery within 28 days of beginning study treatment were ineligible for enrollment. Patients were also unable to enroll on the trial if they had clinically significant cardiac disease, dementia or altered mental status affecting the ability to provide informed consent, or uncontrolled hypertension.

Oncolytics Biotech® receives FDA fast track designation for pelareorep in 2L KRAS-mutant MSS metastatic colorectal cancer. News release. Oncolytics Biotech Inc. February 4, 2026. Accessed February 5, 2026. https://tinyurl.com/7br4n9m5

Oncolytics Biotech highlights strong efficacy and translational data in metastatic colorectal cancer; will advance regulatory pathway discussions. News release. Oncolytics Biotech Inc. September 8, 2025. Accessed February 5, 2026. https://tinyurl.com/yc839wpx

Study of REOLYSIN in combination with FOLFIRI and bevacizumab in FOLFIRI naive patients with KRAS mutant metastatic colorectal cancer. ClinicalTrials.gov. Updated December 19, 2018. Accessed February 5, 2026. https://tinyurl.com/bdekvwbp

Prior phase 1 data support the fast track designation for pelareorep as a treatment for those with KRAS-mutated microsatellite stable colorectal cancer.