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Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT) N-of-1 Precision Oncology Study: Molecular Profiling to Match Individually Dosed, Personalized Drug Combinations

Year: 2026

Type: article

Abstract: PURPOSE Malignancies have complex and distinct molecular profiles that may not segregate by tumor type. However, most precision oncology treatments are matched to a single biomarker. We aimed to optimize therapy for advanced cancers using individually dosed drug regimens customized to cotarget multiple molecular alterations. METHODS Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT; NCT02534675 ) is a prospective, investigator-initiated, multidepartment/pan-cancer trial for aggressive advanced/metastatic malignancies. Patients had tissue and/or blood next-generation sequencing (NGS; Foundation Medicine). A molecular tumor board made suggestions. Degree of biomarker matching to drugs given was calculated by a matching score (MS; broadly, number of pathogenic alterations targeted divided by total pathogenic alterations). RESULTS Overall, 210 evaluable patients (n = 456 consented) received ≥1 US Food and Drug Administration–approved drug (mostly off label) after NGS. Median number of pathogenic alterations/tumor was five (range, 0-20); approximately 95% of patients had unique molecular landscapes. Consistent with I-PREDICT's objective to optimize/tailor treatment for each patient, we administered 157 different regimens (including 103 personalized combinations without established safety/dosing data). For previously unstudied combinations, starting doses were reduced and titrated to tolerance (intrapatient dose-finding); only 6.5% experienced Grade 3/4 drug-related toxicities ( v 15.5% of those receiving established regimens). Higher disease control rate (stable disease ≥6 months/objective response), and longer progression-free survival and overall survival correlated significantly/independently/linearly with greater degrees of drug matching to alterations (higher MS), but did not vary by drug number or dosages. CONCLUSION The I-PREDICT strategy of maximizing personalized biomarker matching with individually dosed customized drug combinations enabled safe and active N-of-1 matched treatment, including regimens previously unstudied in Phase I trials. I-PREDICT represents a blueprint for a new personalized precision oncology paradigm, which merits validation via additional prospective trials.

Source: Journal of Clinical Oncology

DOI: 10.1200/jco-25-01453