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OncoMatch/Clinical Trials/NCT05332561

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

Is NCT05332561 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments for early-stage breast cancer.

Phase 2RecruitingGerman Cancer Research CenterNCT05332561Data as of May 2026

Treatment: Atezolizumab 1200 mg in 20 ML · Inavolisib · Ipatasertib · Olaparib · Sacituzumab govitecan · Trastuzumab/pertuzumabIn 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.

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Extracted eligibility criteria

Cancer type

Breast Carcinoma

Biomarker criteria

Required: PD-L1 (CD274) positivity (IHC ≥1% on immune cells within the tumor) (IHC ≥1% on immune cells)

PD-L1 positivity measure by IHC (≥1% on immune cells within the tumor)

Required: PD-L1 (CD274) amplification

CD274 amplification

Required: PIK3CA known/reported oncogenic mutation

Known/reported oncogenic mutation in PIK3Ca

Required: AKT1 aberration predicting increased PI3K-AKT pathway activity except PI3K-mutations

Aberrations predicting increased PI3K-AKT pathway activity except PI3K-mutations

Required: BRCA1 inactivating somatic or germline mutation including homozygous deletions

Inactivating somatic or germline BRCA1/2 mutation including homozygous deletions

Required: BRCA2 inactivating somatic or germline mutation including homozygous deletions

Inactivating somatic or germline BRCA1/2 mutation including homozygous deletions

Required: PALB2 inactivating germline mutation

Inactivating germline PALB2 mutations

Required: TACSTD2 overexpression

Trop-2-overexpression (with IHC and except known/reported homozygous polymorphism in UGT1A1*28)

Required: HER2 (ERBB2) exon-20 insertion

HER2 exon-20 insertion

Required: HER2 (ERBB2) activating mutation

Activating HER2-mutation

Disease stage

Required: Stage I, II, III

Performance status

ECOG 0–1(Restricted strenuous activity)

Prior therapy

Must have received: neoadjuvant chemotherapy — neoadjuvant

Conducted neoadjuvant chemotherapy

Must have received: surgery — post-neoadjuvant

conducted neoadjuvant chemotherapy and surgery

Must have received: post-neoadjuvant treatment — post-neoadjuvant

conducted standard post-neoadjuvant treatment +/- radiotherapy (standard according to German guidelines except Abemaciclib and Olaparib)

Lab requirements

Blood counts

adequate bone marrow function defined by laboratory tests

Kidney function

adequate renal function defined by laboratory tests

Liver function

adequate hepatic function defined by laboratory tests

Structured fields extracted by AI. May contain errors — verify against the official protocol.

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