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

Sep 22, 2026

Advanced cancers show complex molecular profiles that often cannot be categorized by tumor type, and most precision oncology approaches match treatment to a single biomarker. The study optimized individualized therapy by using individually dosed drug regimens that co-target multiple molecular alterations, guided by an evidence-based matching score. The trial tested a pan-cancer, N-of-1 strategy and evaluated safety, biomarker matching, disease control, and survival outcomes, linking better matching with improved clinical performance.

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Original Reports | Genomics/Proteomics 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 Jason K. Sicklick, MD1,2,3 ; Daisuke Nishizaki, MD3,4 ; Hirotaka Miyashita, MD5 ; Ryosuke Okamura, MD6 ; Michael E. Hahn, MD7; Mina Nikanjam, MD, PhD3,4 ; Paul T. Fanta, MD3,4; David E. Piccioni, MD3,8; Hitendra Patel, MD3,4 ; Ramez N. Eskander, MD3,9 ; Rana R. McKay, MD3,4 ; Jeffrey S. Ross, MD10,11 ; J. Jack Lee, PhD, MS, DDS12 ; Scott M. Lippman, MD3,4 ; Shumei Kato, MD3,4 ; and Razelle Kurzrock, MD13 DOI [https://doi.org/10.1200/JCO-25-01453](https://doi.org/10.1200/JCO-25-01453) | 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 5 456 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 ordosages. | | 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. | ACCOMPANYING CONTENT Editorial, p. 515 Data Sharing Statement Data Supplement Protocol Accepted October 28, 2025 Published January 8, 2026 J Clin Oncol 44:540-552 © 2026 by American Society of Clinical Oncology View Online Article Creative Commons Attribution Non-Commercial No Derivatives 4.0 License INTRODUCTION Personalized oncology is deﬁned as customizing treatments to individual patients. This is a natural extension of precision oncology, which is based upon molecular proﬁling to precisely identify pharmacologically tractable tumor alterations. Signiﬁcant initial headway has been made in precision oncology by targeting speciﬁc molecular disease subsets (eg, ALK inhibitors for ALK fusion-positive lung cancer) .1 Notably, however, many molecular driver events 540 | Volume 44, [Issue 7 |](Issue 7 | ascopubs.org/journal/jco)[ ascopubs.org/journal/jco](Issue 7 | ascopubs.org/jour

FAQs

What problem does I-PREDICT address in precision oncology?

Many cancers have molecular profiles that do not align neatly with a single tumor type, and most precision oncology treatments match only one biomarker. I-PREDICT aims to improve treatment by targeting multiple molecular alterations for each patient.

How were patients assigned to individualized treatments in the study?

Patients underwent tissue and/or blood next-generation sequencing, and a molecular tumor board suggested regimens. A matching score quantified how well targeted alterations matched the administered drugs.

What relationships did the study find between matching and clinical outcomes?

Higher degrees of drug matching to molecular alterations correlated with better disease control and longer progression-free and overall survival. These outcomes did not vary by the number of drugs or starting doses.

Sep 22, 2026

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