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Updated: Jun 9, 2026

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies
13:24

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Comprehensive Molecular and Genomic Analysis of NCI-MATCH Subprotocol Y: Capivasertib in Patients With an AKT1

Carolyn K McCourt1, Jacob Gross2, Kevin Kalinsky3

  • 1Department of Obstetrics & Gynecology, Washington University School of Medicine, St Louis, MO.

JCO Precision Oncology
|March 28, 2025
PubMed
Abstract

Insights

Capivasertib showed a 36% objective response rate in advanced tumors with AKT1 E17K mutations. TP53 mutations may predict response, while PI3K/AKT/mTOR pathway alterations and EGFR overexpression suggest resistance.

Area of Science:

  • Oncology
  • Genomics
  • Precision Medicine

Background:

  • NCI-MATCH (EAY131) is a precision medicine trial matching advanced cancer patients to targeted therapies.
  • Arm Y investigated capivasertib, a pan AKT inhibitor, for tumors with AKT1 E17K mutations.

Purpose of the Study:

  • To conduct a molecular and genomic analysis of patient specimens.
  • To identify potential biomarkers for response or resistance to capivasertib.

Main Methods:

  • Whole-exome and RNA sequencing of 25 pretreatment tumor samples.
  • Analysis of gene set and pathway enrichment in responders versus nonresponders.
  • Evaluation of objective response rate (ORR) as the primary endpoint.

Main Results:

  • Capivasertib demonstrated a 36% ORR in the translational cohort (9/25 patients).
  • TP53 mutations were more frequent in responders.
  • PI3K/AKT/mTOR pathway genes (TYRO3, SYNJ1, CDIPT) and EGFR overexpression were associated with nonresponse.

Conclusions:

  • Capivasertib achieved a clinically significant ORR in AKT1 E17K-mutated tumors.
  • TP53 mutations may predict response to capivasertib.
  • Further research into predictive biomarkers for capivasertib is necessary.

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