UC San Diego trial shows tumor DNA-guided drug combinations can personalize care for advanced cancer patients

A trial built around individual tumor genetics

Researchers at the University of California San Diego School of Medicine reported results from a prospective clinical trial designed to individualize cancer treatment using the DNA profile of each patient’s tumor. The trial, called Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT), evaluated whether multi-drug regimens could be tailored to a person’s specific set of tumor alterations, rather than relying on a standardized approach.

The findings were published online on January 8, 2026 in the Journal of Clinical Oncology. The study evaluated patients with aggressive advanced or metastatic cancers who underwent next-generation sequencing of tumor tissue and/or circulating tumor DNA, followed by treatment planning informed by molecular findings.

What the study tested in practice

Unlike many precision oncology strategies that match a single drug to a single biomarker, I-PREDICT sought to co-target multiple pathogenic alterations within the same tumor using combinations of existing, FDA-approved therapies. Treatment selection was supported by a multidisciplinary molecular tumor board, while the final regimen and feasibility considerations reflected real-world clinical constraints such as comorbidities, toxicity risks, medication access and insurance coverage.

• Patient cohort: 210 evaluable patients with advanced cancers received at least one FDA-approved drug after molecular testing; 456 patients consented overall.

• Tumor diversity: Nearly 95% of patients had a unique molecular profile, underscoring the difficulty of applying a single template to many advanced cancers.

• Regimen variety: Clinicians administered 157 different treatment regimens, including 103 personalized drug combinations that did not have established safety or dosing data in that pairing.

Dosing strategy and safety signals

For combinations lacking established dosing guidance, the study used a cautious approach: reduced starting doses followed by intrapatient dose escalation to tolerance. Reported rates of severe (grade 3/4) drug-related toxicities were 6.5% among those receiving previously unstudied combinations, compared with 15.5% among patients receiving established regimens, as defined in the study’s analysis.

The trial’s core premise was that maximizing how closely drugs match an individual tumor’s actionable alterations can be operationalized in routine care settings, even when multiple agents are used.

How outcomes tracked with “matching” the therapy

The study quantified how extensively a patient’s regimen targeted the tumor’s identified pathogenic alterations using a matching score. Higher matching scores were associated with better disease control and longer progression-free and overall survival. The analysis reported that these associations were significant and did not simply reflect using more drugs or higher doses.

What this could mean for precision oncology

For clinicians and patients confronting advanced cancers with complex molecular drivers, the results add clinical trial evidence supporting an individualized, combination-based precision oncology strategy. The authors described the approach as a framework that warrants validation in additional prospective trials designed to confirm benefits, clarify which patients benefit most, and define how broadly such individualized regimens can be implemented across health systems.