NCT05332561

Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE)

Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer - a Multicenter, Open-label, Umbrella Phase-II Study - COGNITION-GUIDE

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: German Cancer Research Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In early breast cancer (eBC), pathological complete response (pCR) after neoadjuvant therapy acts as surrogate marker for metastasis and overall survival. Therapy intensification by adding an adjuvant therapy line (post-neoadjuvant treatment) substantially lowers the risk of relapse in high-risk breast cancer patients with residual disease after neoadjuvant treatment (non-pCR). While this approach was exemplified in two phase III trials without biomarker-stratification (CREATE-X, KATHERINE), even higher efficiency might be achieved by individualized genomic-guided post-neoadjuvant therapies. Within the seven-arm umbrella phase-II clinical trial COGNITION-GUIDE, we aim to deliver molecularly-tailored cancer care by implementing an additional response- and genomics-guided post-neoadjuvant therapy after finishing the guideline-compliant post-neoadjuvant treatment in high-risk breast cancer patients with residual cancer burden after neoadjuvant therapy to reduce the substantial risk of local and distant relapse. The trial evaluates not a single drug but rather a general strategy of precision oncology in the curative setting and provides the basis for future confirmatory biomarker-driven trials. Allocation to the therapy-arms is conducted by in depth molecular characterization of tumors within the COGNITION registry program. The study aims to show an overall benefit of the precision medicine approach in high-risk eBC patients and to allow for secondary exploratory evaluation of each study-arm. The primary endpoint of the study is invasive Disease-Free Survival (IDFS) after 4 years measured from surgery to local or distant relapse or death. The sample size of the entire trial is 240 eligible patients.

Detailed description

In early breast cancer (eBC), pathological complete response (pCR) after neoadjuvant therapy acts as surrogate marker for metastasis and overall survival. Therapy intensification by adding an adjuvant therapy line (post-neoadjuvant treatment) substantially lowers the risk of relapse in high-risk breast cancer patients with residual disease after neoadjuvant treatment (non-pCR). While this approach was exemplified in two phase III trials without biomarker-stratification (CREATE-X, KATHERINE), even higher efficiency might be achieved by individualized genomic-guided post-neoadjuvant therapies. To date, prospective whole genomic and transcriptomic sequencing in the framework of precision oncology concepts is predominantly conducted in advanced-stage cancer, limiting the overall benefit mainly to prolongation of progression-free survival rather than cure. In contrast, the implementation of precision oncology in an early disease stage may empower targeted intervention based on high throughput sequencing at a time point with low tumor burden and limited clonal complexity, harbouring the prospect to substantially improve cure rates by prohibition of incurable metastasis. Whole-genome (WGS), whole exome (WES), gene panel and transcriptome sequencing in the molecular diagnostic registry platform COGNITION (neoadjuvant-treated eBC patients) revealed relevant diagnostic information on molecular-druggable alterations in a substantial proportion of patients in different molecular pathways (e.g. phosphatidylinositol 3-kinase (PI3K)/ serine/threonine kinase (AKT), Mitogen-activated protein kinase (MAPK), apoptosis, DNA-repair, immune escape etc.). Within the seven-arm umbrella phase-II clinical trial COGNITION-GUIDE, we aim to deliver molecularly-tailored cancer care by implementing an additional response- and genomics-guided post-neoadjuvant therapy after finishing the guideline-compliant post-neoadjuvant treatment in high-risk breast cancer patients with residual cancer burden after neoadjuvant therapy to reduce the substantial risk of local and distant relapse. The trial evaluates not a single drug but rather a general strategy of precision oncology in the curative setting and provides the basis for future confirmatory biomarker-driven trials. Eligible patients are identified considering pCR-status and clinical stage estrogen receptor status grade (CPS-EG)-score following surgery after neoadjuvant therapy. Allocation to the therapy-arms is conducted by in depth molecular characterization of tumors within the COGNITION registry program. Recruitment of adequate patient numbers in well-defined molecular subgroups is achieved in a multicenter approach. The study aims to show an overall benefit of the precision medicine approach in high-risk eBC patients and to allow for secondary exploratory evaluation of each study-arm. The primary endpoint of the study is invasive Disease-Free Survival (IDFS) after 4 years measured from surgery to local or distant relapse or death. The sample size of the entire trial is 240 eligible patients.

Conditions

• Early-stage Breast Cancer

Interventions

Type	Name	Description
DRUG	Atezolizumab 1200 mg in 20 ML Injection	Arm 1
DRUG	Inavolisib	Arm 2
DRUG	Ipatasertib	Arm 3
DRUG	Olaparib	Arm 4
DRUG	Sacituzumab govitecan	Arm 5
DRUG	Trastuzumab/pertuzumab	Arm 6

Timeline

• Start date: 2023-06-29
• Primary completion: 2030-03-01
• Completion: 2030-12-01
• First posted: 2022-04-18
• Last updated: 2025-03-20

Locations

9 sites across 1 country: Germany