Clinical trial enrollment in oncology can be complex, and the challenge becomes even greater in heavily pretreated patient populations.
For individuals with platinum-resistant or platinum-refractory ovarian cancer, trial participation often comes after several prior therapies, disease recurrence and repeated cycles of uncertainty.
President and CEO
Genelux
Xtalks spoke with Tom Zindrick, President and Chief Executive Officer of Genelux, about how clinical trials can better engage patients and investigators in difficult-to-treat cancers, particularly in late-line ovarian cancer.
For Zindrick, one of the most important enrollment lessons is that sponsors must recognize what patients have already been through before they arrive at a trial site.
Zindrick explained that the cancer journey can be a roller coaster, receiving a diagnosis, starting therapy, potentially seeing a response which offers hope and then facing the disappointment of recurrence before moving on to the next treatment.
According to a 2024 Journal of Clinical Oncology analysis, only an estimated 7.1% of adult cancer patients participate in cancer treatment trials. In oncology, the patients most in need of new treatment options are often the ones facing the greatest barriers to clinical trial participation. This is especially true in ovarian cancer, where 54% of cases in the US are diagnosed after the disease has metastasized. The five-year relative survival for ovarian cancer is 52%, which drops to just 31.5% for distant-stage disease. As patients move through multiple lines of therapy, it becomes important to consider whether studies are feasible for this cohort of patients.
Genelux is developing Olvi-Vec, an investigational oncolytic immunotherapy being evaluated in platinum-resistant/refractory ovarian cancer. In the company’s ongoing Phase III OnPrime/GOG-3076 trial, Olvi-Vec, followed by platinum-doublet chemotherapy and bevacizumab, is being compared with physician’s choice chemotherapy and bevacizumab. The trial remains on track for topline data in the second half of 2026.
In Genelux’s Phase II VIRO-15 study, patients had a median of four prior lines of therapy, ranging from two to nine. The nonrandomized study, published in JAMA Oncology, evaluated intraperitoneal Olvi-Vec followed by platinum-doublet chemotherapy with or without bevacizumab in 27 patients with platinum-resistant or platinum-refractory ovarian cancer. Results showed a 54% objective response rate by RECIST 1.1, median progression-free survival (PFS) of 11 months and median overall survival of 15.7 months.
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Reducing Friction for Patients and Sites
In late-line oncology trials, logistical complexity can become a barrier to participation. Frequent visits, travel, long appointments, testing requirements and uncertainty around randomization can all weigh heavily on patients and caregivers.
Zindrick said that in addressing patient burden, “The first part is reducing friction, starting with the clinical trial design.” This means evaluating whether the questions being asked not only satisfy regulators, but also account for the burden placed on patients.
That can include simplifying visits, considering telehealth where appropriate, exploring whether some labs can be done outside the clinic and providing clearer patient-facing materials.
Zindrick said Genelux developed a patient journey document to help participants understand what to expect from the first clinic visit through long-term follow-up. Support may also include transportation, meals, lodging and caregiver engagement.
The same philosophy applies to clinical trial sites. Oncology sites are under pressure from competing studies, staffing constraints and the operational demands of increasingly complex protocols. Zindrick said sponsors need to make the rationale for participation clear while also making trial execution manageable.
“For both patients and clinicians, you start with ‘the why.’ With all that’s out there, why should they do this study?” he said. “But equally important is the ‘how.’ How do we make this a study that is not overly burdensome?”
Designing Oncology Trials Around Patients Who Are Often Excluded
Many oncology trials limit the number of prior therapies patients can have received, partly to reduce clinical heterogeneity and safety risk. But those criteria can also exclude patients with few remaining options.
Zindrick highlighted Genelux’s approach as a key differentiator, noting that the OnPrime study does not require a biomarker and does not cap the number of prior lines of therapy.
The trial’s patient-facing materials similarly note that there is no cap on the number of prior therapy lines, no requirement for a specific tumor receptor or ligand and no limitation based on BRCA, homologous recombination or mismatch repair status.
For late-line ovarian cancer, this broader approach reflects both a clinical challenge and a development strategy. Tumors in heavily pretreated patients are often heterogeneous because patients have received different therapies, responded for different durations and accumulated different resistance mechanisms. That heterogeneity can complicate trial interpretation, but it also makes controlled evidence especially important to demonstrate substantial evidence of effectiveness.
Genelux has said the OnPrime trial is intended to generate controlled clinical evidence to support a potential regulatory filing if successful. The OnPrime trial is designed with 2:1 randomization, meaning two out of every three participants are assigned to the experimental arm, Zindrick explained. He said site teams play a major role in preparing patients for the possibility of being randomized to the comparator arm, especially when they may already feel they have exhausted standard options.
That makes communication central to trial conduct. Patients need to understand not only the scientific rationale, but also the purpose of randomization and the contribution their participation may make for future patients.
“It Starts With Hope”
In Zindrick’s view, trial awareness and education in advanced cancer begin with a simple but powerful concept.
“It starts with hope. When patients have hope, they’re going to be more open-minded, where they might otherwise be at a point where they are saying, ‘I’m kind of done. I can’t go through this roller coaster anymore.’”
For sponsors, translating hope into participation requires more than promotional outreach. Zindrick pointed to work with advocacy groups, cooperative groups, trial sites and targeted awareness campaigns, all conducted within institutional review boards and regulatory guardrails.
The goal is to explain why a trial is different, why it matters and how participation will be supported. This is particularly relevant for modalities that may not fit neatly into established categories.
Endpoints, Evidence and Regulatory Expectations
The discussion around late-line oncology trials is also changing at the regulatory level. Overall survival remains the gold standard in oncology, but trials increasingly rely on endpoints such as PFS when they are clinically meaningful, measurable earlier and supported by a strong evidentiary package.
The FDA has also issued draft guidance describing how one adequate and well-controlled clinical investigation, combined with confirmatory evidence, can be used to meet the substantial evidence requirement for drug and biologic approvals.
More recently, FDA leaders described one robust pivotal trial plus confirmatory evidence as a new default option for approval, with confirmatory evidence potentially including mechanistic science, related-indication data, animal models, real-world evidence or a second adequate and well-controlled study.
For smaller biotech companies, this evolving framework could be meaningful if it allows a rigorous randomized trial to carry more regulatory weight, particularly in high-unmet-need settings. But it also raises the bar for study design, trial execution and endpoint credibility.
Zindrick said Genelux has been careful to protect trial integrity, noting that the company is blinded to its ongoing Phase III results and focused on maintaining high fidelity in execution.
Innovation Must Serve the Trial Question
Clinical trial innovation is often associated with hybrid models, telehealth, digital tools, adaptive designs, Bayesian statistics and now AI. Zindrick sees potential in several of these areas, particularly approaches that can help sponsors reach clear answers faster and avoid exposing patients to ineffective therapies.
Adaptive design and Bayesian methods may help clinical researchers use data more efficiently in certain settings, provided the historical or external evidence is appropriate and aligned with the study question. But Zindrick also cautioned against overpromising, particularly with AI in clinical development.
“On the clinical side, I think it’s still very much to be determined,” he said, adding that AI may already have clearer use cases in early drug discovery, including structure-activity relationship work, and in facilitating regulatory reviews.
His takeaway is pragmatic: “It’s the right tool for the right job.”
Trial innovation is not valuable simply because it is technologically advanced. It is valuable when it reduces burden, improves access, strengthens endpoint interpretation, accelerates decision-making or makes a study more feasible without compromising scientific rigor.
A More Patient-Centered Model for Difficult-to-Treat Cancers
The future of clinical trials in advanced ovarian cancer and other difficult-to-treat tumors will likely depend on the balance between rigor and realism.
Sponsors must generate evidence that regulators can trust, while designing studies that patients can realistically participate in and sites can operationalize.
For heavily pretreated patients, that means building protocols around the reality of fatigue, travel burden, caregiver needs, emotional strain and limited treatment windows. For investigators, it means clearly articulating why a trial matters and making execution as efficient as possible. For regulators and sponsors, it means aligning on endpoints and evidence standards early enough to avoid unnecessary duplication while still producing interpretable results.
As Zindrick’s perspectives suggest, the most effective trial designs in late-line oncology may be those that begin not with technology or protocol complexity, but with a more basic question: how do we give patients and investigators a credible reason to keep going?
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