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None\n Biomarkers are redefining how oncology trials are designed, shifting from single-mutation targeting to comprehensive genomic profiling that enables more precise, patient-centric approaches. In this episode of The Top Line, Allucent’s Dr. Danielly Vicente explores how these advances are improving patient selection, accelerating trial efficiency, and increasing the likelihood of clinical success. From basket and umbrella trials to adaptive designs, biomarker-driven strategies are helping researchers match the right therapies to the right patients faster than ever before.  The conversation also dives into the operational realities behind these innovations. While genomic testing and biomarker screening offer powerful insights, they introduce challenges in data integration, trial logistics, and patient enrollment. Dr. Vicente shares how hybrid testing models, molecular tumor boards, and CRO expertise are helping organizations overcome these hurdles and streamline development. Looking ahead, emerging technologies like circulating tumor DNA (ctDNA) and multiomic profiling are poised to further transform oncology trials. These tools enable real-time monitoring, adaptive decision-making, and more personalized treatment strategies, bringing the industry closer to truly individualized cancer care. Listen to the full interview to understand what’s next for biomarker-driven development.Speaker 1:You\'re listening to a sponsored episode of The Top Line.Stephanie Butler:Welcome everyone. You are listening to The Top Line brought to you by Fierce Biotech. I\'m your host, Stephanie Butler. Today\'s episode is sponsored by Allucent, and our topic of conversation today is advanced biomarker strategies in oncology trials from patient selection to ongoing monitoring. I\'ll be joined by Danielly Vicente, who is the associate medical director of oncology and hematology at Allucent.So welcome, Danielly.Dr. Danielly Vicente:Hi, everyone. Hi, Stephanie. It\'s very nice to be here. I\'m glad to be here talking about this fantastic topic today. So I\'m Danielly Vicente. I\'m a hematologist and oncologist. I have over 15 years of clinical practice with oncology patients, and I\'m absolutely amazed by how precision medicine has evolved over the last years. I\'m currently medical director at Allucent, and I work closely with early phase trial design, which gives me a unique vantage point to bridge molecular science to real world clinical outcomes.Stephanie Butler:You\'re right. If I think back 20 years when we were talking about some of the development of some of these things in precision medicine, where it has come, especially in the past few years, it\'s kind of astronomical.So I kind of want to start. Thank you again, Dr. Vicente, for being here. I want to start with how has the role of biomarkers and oncology trial design evolved over this past decade?Dr. Danielly Vicente:Biomarkers in oncology trials have shifted from targeting single mutations like KRAS, EGFR, to comprehensive genomic profiling, identify multiple actionable alterations across tumor types. This evolution has supported targeted therapies such as BRAF inhibitors  explored in non-small cell lung cancer and therapies like checkpoint inhibitors.Also, trial designs have advanced. We have now basket trials that test therapies across cancer sharing biomarkers, while we also have umbrella trials that evaluate multiple therapies within one cancer type. I have a good example. This is HER2 low breast cancer. These patients represent about 50% of cases, and they were previously deemed HER2 negative and limited to chemotherapy or endocrine therapy with suboptimal outcomes.Now, trastuzumab, an antibody drug conjugate targets these low HER2 tumors. In the DESTINY-Breast04 trial, that was performed in 557 pretreated patients, it doubled the  median PFS to 10 months versus five with chemotherapy. The FDA also expanded approval to HER2 ultra low cases following DESTINY-Breast06 which showed PFS of 13 versus eight months with  these patients.Stephanie Butler:Wow, that\'s a great example. You\'re talking about the trial design, but we know that patient selection is still the cornerstone of any biomarker driven development. So when you\'re translating those biomarker strategies into practice, then how are they influencing patient identification and enrollment, especially if you\'re talking about early phase oncology trials?Dr. Danielly Vicente:Critical priority in early drug development is optimizing patient selection to accelerate efficacy signals while mitigating toxicity risks. So currently, less than 10% of oncology drugs entering phase one trials ultimately receive regulatory approval. This rate may be even lower for immunotherapies due to their biological and clinical complexities. The development of immunotherapy agents is a highly complex, time-intensive and costly process.Large scale genomic screening initiatives such as NCI-MATCH can identify patients with rare mutations enabling enrollment in biomarker-driven trials. They match patients to trials, increasing enrollment for those with rare mutations. We had this comprehensive analysis, which reviewed over 17,000 oncology drug development trajectories from 2000 to 2015, and they found that trials using biomarkers had also almost twice the overall possibility of success compared to trials without biomarkers, it was 10% versus around 5%.Stephanie Butler:That\'s a big difference.Dr. Danielly Vicente:Yeah, it\'s very different. So while the use of biomarkers in the stratification of patients improved the possibility of success in all phases, it\'s most significant in phases one and two. But however, despite advancements, many patients fail screening due to the absence of actionable biomarkers. This highlights the need for efficient screening processes. We have panels like FoundationOne that are being used to test multiple genes simultaneously, improving the efficiency of patient selection. Also, pre-screening tests via electronic medical records and cancer registries, they identify eligible patients early without full trial screening. So using biomarkers already in standard panels avoid new tissue biopsies and enables rapid assessment from archival samples or blood.A very interesting strategy is to have a molecular tumor board where physicians from many specialties, like oncologists, surgeons,  radiation oncologists, they can review and discuss the most common molecular abnormalities, the available tests, available research protocol in the institution, and also push the health  insurers for reimbursements.Stephanie Butler:That\'s a great idea, especially when patient selection is so critical. I think going a little bit beyond patient selection, how are biomarkers now shaping the design of the early stage oncology trials today?Dr. Danielly Vicente:Biomarkers are fundamentally shaping early stage oncology trial designs by enabling enriched cohorts, expansion on phases, adaptive reassignments, and data-driven decisions that accelerate development and improve efficiency. So expansion cohorts, for example, extend phase one safety data to efficacy testing in subgroups. We have, for example, BATTLE trial where 11 biomarkers guided adaptive randomization to four therapies in lung cancer, identifying biomarker specific responses.Adaptive trial strategies reassign progressed patients to new arms using dynamic endpoints like PFS ratios and ctDNA changes for intra-patient comparisons. Biomarkers also inform early go, no-go decisions through real-time  resistance metrics and transcriptomic shifts, for example. In adaptive trial strategies, they use this pre-specified interim analysis to modify parameters such as  sample size, treatment arms, or patient\'s populations. And this is all based on accumulating data. This enables what I talked about, the go, no-go decisions informed by biomarkers.We have another example in ER-positive HER2-negative breast cancer. Approximately 20% of cases have low NF1 expression, which is associated with endocrine therapy resistance, but elevated CDK4/6 activity. So preclinical studies demonstrated that NF1 low ER positive tumors are sensitive to palbociclib combined with fulvestrant, showing durable regressions in patient-derived xenograft models. So this biomarker could inform adaptive enrichment strategies to identify responsive patients early. And these approaches, they reduce the screen failures and support regulatory approvals. They also help find the most effective treatment with less side effects, or in other words, the right drug for the right patient.Stephanie Butler:It\'s so interesting that if you think about how to use them, they can actually change how you actually design your trials, and that will benefit everyone down the road. I kind of want to move on a little bit and look at it from the clinical development perspective. So from that perspective, what challenges arise when you\'re incorporating genomic testing and also the biomarker screenings into trials?Dr. Danielly Vicente:Incorporating genomic testing and biomarker screening into trials presents some challenges. The central debate is centralized versus local testing. Centralized NGS, for example, ensures standardization, but longer turnaround times and delays in obtaining genetic tests results,  and this genetic test results can impact trial timelines and patient enrollment. Local testing offers speed though with potential variability. So a hybrid approach mitigates these trade-offs using local labs for rapid eligibility screening and central labs for confirmatory validation, for example. So this balances speed with rigor, accelerating enrollment while maintaining endpoint verification.Also, beyond testing logistics, data integration and interpretation add complexity. Diagnostic coordination between labs, sites, and patients adds operational complexities, and incorporating biomarker screening requires robust infrastructure, trained personnel, and streamlined workflows, which can be resource intensive. Here, a dedicated CRO helps mitigate these challenges by providing centralized lab networks for hybrid testing,  vendor coordination,  build infrastructure such as biobanks, bioinformatics, and expertise in patient matching to reduce failures. This helps accelerate enrollment in these genetics-based trials while ensuring the regulatory compliance.Stephanie Butler:I think it\'s important to use these technologies, but there are definitely some challenges. So anyone who can help in that regard is always advantageous because we want to be able to get better treatments for the patients, better outcomes. And so I really appreciate what you guys are doing in this space.I want to kind of look a little bit toward the future, which is what biomarkers and which biomarker technologies or approaches are most likely to influence oncology trial design in the next few years from your perspective?Dr. Danielly Vicente:We have circulating tumor DNA analysis, minimal residual disease detection, real-time biomarker monitoring and multiomic strategies. These are biomarker technologies most likely to influence oncology trial design in the next few years by enabling non-invasive detection, dynamic response assessment, and personalized adjustment.ctDNA analysis provides a non-invasive window into tumor genetics, monitoring treatment response and identifying acquired resistance mechanisms. For example, ESR1 mutations emerge in ctDNA as a mechanism of endocrine therapy resistance in ER-positive breast cancer, reducing aromatase inhibitors\' efficacy. These patients now qualify for oral SERDs like elacestrant, FDA approved in 2023 for ESR1 mutant metastatic breast cancer post-endocrine therapy. Real-time ctDNA monitoring enables adaptive trial designs and MRD-based enrichment strategies, particularly in phase two studies to identify patients with emerging resistance or optimal response. MRD negativity is now recognized as a surrogate endpoint, reasonably likely to predict progression-free survival, supporting accelerated approval pathways and expediting drug availability.I was talking about multiomic strategies. They integrate genomics, proteomics, and tumor microenvironment factors for holistic profiling. Together, these approaches optimize endpoints, reduce screen failures, and support regulatory decisions, advancing what we call truly personalized cancer care, like delivering the right treatment to the right patient at the right time. This is what we want.Stephanie Butler:Of course. And I feel like we\'re starting to actually get there into that real personalized medicine. We maybe still have a few little ways to go, but just some really exciting developments.This has been great. Thank you so much to Allucent and to Dr. Vicente for such a fabulous conversation. Really looking forward to seeing what\'s going to happen in the next couple of years as we move forward with the science in this space.And thank you to all of you for joining us on this episode of The Top Line. I\'m your host, Stephanie Butler, and that\'s the bottom line from The Top Line.