Early-stage Breast CancerPhase 2NCT05332561
Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE)
A Phase 2 study testing Atezolizumab 1200 mg in 20 ML Injection, Inavolisib and Ipatasertib in people with Early-stage Breast Cancer, run by German Cancer Research Center at 9 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Early-stage Breast Cancer
- What is being tested?
- Atezolizumab 1200 mg in 20 ML Injection, Inavolisib and Ipatasertib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 9 sitesGermany
- Study dates
- 29 Jun 2023to Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written informed consent
- Female and male patients with non-metastatic early (stage I-III) breast cancer aged ≥ 18 years
- Conducted neoadjuvant chemotherapy and surgery as well as conducted standard post-neoadjuvant treatment +/- radiotherapy (standard according to German guidelines except Abemaciclib and Olaparib)
- For patients with initially triple negative (TNBC) or HER2-positive breast cancer:
- Non-pCR defined as other than ypT0/is ypN0
- For patients with initially hormone receptor positive and HER2-negative breast cancer: Non-pCR and CPS-EG score
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- ≥ 3 and ypN0, or
- ≥ 2 and ypN+
- ECOG Performance Status ≤ 1
- Acute effects of any prior therapy resolved to baseline severity or National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade ≤ 1 except for adverse effects not constituting a safety risk by investigator judgement
- Postmenopausal or evidence of non-childbearing status. For women of childbearing potential negative urine pregnancy test at post-operative screening and baseline as well as highly effective forms of contraception have to be in place thereafter
- Evidence of childbearing potential is defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile
- Postmenopausal or evidence of non-childbearing status is defined as:
- Amenorrhea for 1 year or more without an alternative medical cause following cessation of exogenous hormonal treatments plus follicle stimulating hormone (FSH) levels in the postmenopausal range in women not using hormonal contraception or hormonal replacement therapy
- Chemotherapy-induced menopause
- Surgical sterilisation (bilateral oophorectomy, bilateral salpingectomy, total hysterectomy or tubal ligation at least 6 weeks before IMP treatment)
- Female patients with age ≥ 60 years
- A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy
- Female patients of childbearing potential and male patients with partners of childbearing potential who are sexually active must agree to the use of two forms of contraception in combination (male condom and one highly effective method). These should be started immediately after signing the informed consent form and continued throughout the period of study treatment plus a substance-depending time period (see respective sub-protocol) for female patients and a substance-depending time period for male patients. Details on contraception and pregnancy testing for male and female patients (and if indicated their partners) under IMP treatment are described within the respective sub-protocol
- Ability of patient to understand and comply with the protocol for the duration of the study, including treatment and scheduled visits and examinations
- Adequate bone marrow, renal, and hepatic function defined by laboratory tests*
- The biomarker-guided eligibility for the respective study arm is evaluated and determined exclusively by the NCT molecular tumor board on the basis of results of the COGNITION molecular diagnostic registry platform. Biomarkers that allow inclusion in the respective arm are:
- Arm 1 (Atezolizumab, Immune Evasion ): PD-L1 positivity measure by IHC (≥1% on immune cells within the tumor), MSI-high status (validated by PCR), TMB-H (≥10mut/MB), CD274 amplification
- Arm 2 (Inavolisib, PI3K): Known/reported oncogenic mutation in PIK3Ca
- Arm 3 (Ipatasertib, AKT): Aberrations predicting increased PI3K-AKT pathway activity except PI3K-mutations, HR positive histology
- Arm 4 (Olaparib, PARP, DNA-Repair): Inactivating somatic or germline BRCA1/2 mutation including homozygous deletions, Inactivating germline PALB2 mutations
- Arm 5 (Sacituzumab Govitecan, TROP-2): Trop-2-overexpression (with IHC and except known/reported homozygous polymorphism in UGT1A1*28)
- Arm 6 (Trastuzumab / Pertuzumab, ERBBB): HER2 exon-20 insertion, Activating HER2-mutation
Who cannot join
- Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 year
- Concurrent severe, uncontrolled systemic disease that would place patient at undue risk or interfere with planned treatment
- Concurrent participation or previous treatment within 30 days in another interventional clinical trial
- Persistent toxicity (≥ Grade 2 according to NCI CTCAE v5.0 caused by previous cancer therapy, excluding alopecia
- Clinical signs of active infection (> Grade 2 according NCI CTCAE v5.0)
- History of or newly diagnosed human immunodeficiency virus (HIV) infection and immunocompromised patients
Show all 21Show fewer
- Active Hepatitis A virus infection
- Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B surface antigen (HBsAg) test. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening, are eligible for the study if active HBV infection is ruled out on the basis of HBV DNA viral load per local guidelines
- Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test at screening confirmed by a polymerase chain reaction (PCR) positive for HCV RNA
- Dementia or significant impairment of cognitive state
- Epilepsy requiring pharmacologic treatment
- Pregnancy and breast feeding
- Inability to take oral medication and gastrointestinal disorders likely to interfere with absorption of study medication
- Major surgery (any invasive operative procedure in which a more extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered) within four weeks before screening and baseline excluding breast-tumor resection after neoadjuvant chemotherapy. Patients must have recovered from any effects of any major surgery
- Systemic chemotherapy or radiotherapy within four weeks or a longer period depending on the characteristics of the agents used
- Heart failure classified as New York Heart Association (NYHA) II/III/IV
- Severe obstructive or restrictive ventilation disorder
- Patients with clinically active tuberculosis
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug
- Is taking or requiring the continued use of any of the prohibited concomitant medications listed in the respective subprotocols at baseline
- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder or non-malignant systemic disease. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression or, superior vena cava syndrome.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Andreas Schneeweiss, Prof. Dr. contact
Richard Schlenk, Prof. Dr. contact
9 sites in 1 country
Germany9 sites, 9 recruiting
- Recruiting
Universitätsklinikum Augsburg
Augsburg, Bavaria, 86156
NIna Ditsch, Prof. Dr., +49 (0)821 400 165809, nina.ditsch@uk-augsburg.de
- Recruiting
Charité - Universitätsmedizin Berlin
Berlin
Jens Blohmer, Prof. Dr., +49 (0)30 450 564 ext. 172, jens.blohmer@charite.de
- Recruiting
Universitätsklinikum Carl-Gustav-Carus
Dresden, Saxony, 01397
Pauline Wimberger, Prof. Dr., +49 (0)351 458 ext. 6728, Pauline.Wimberger@uniklinikum-dresden.de
- Recruiting
Universitätsklinikum Erlangen
Erlangen, Bavaria, 91054
Peter Fasching, Prof. Dr., +49 (0)9131 85 ext. 33553, peter.fasching@uk-erlangen.de
- Not yet recruiting
Universitätsklinikum Essen
Essen, 45147
Ann-Kathrin Bittner, PD Dr., +49 (0)201 723 2575, ann-kathrin.bittner@uk-essen.de
- Recruiting
National Center for Tumor Diseases
Heidelberg, Baden-Wurttemberg, 69120
Andreas Schneeweiss, Prof. Dr., andreas.schneeweiss@med.uni-heidelberg.de
- Recruiting
Universitätsklinikum Tübingen
Tübingen, Baden-Wurttemberg, 72076
Andreas Hartkopf, Prof. Dr., +49 (0)7071 29-82211, Andreas.Hartkopf@med.uni-tuebingen.de
- Recruiting
Universitätsklinikum Ulm
Ulm, Bavaria, 89075
Wolfgang Janni, Prof. Dr., +49 (0)731 500 ext. 58501, Janni_Studien.UKF@uniklinik-ulm.de
- Not yet recruiting
Universitätsklinikum Würzburg
Würzburg, Bavaria, 97080
Achim Wöckel, Prof. Dr., +49 (0)931 201 25250, woeckel_a@ukw.de
About this study
Official title: Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer - a Multicenter, Open-label, Umbrella Phase-II Study - COGNITION-GUIDE
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.
Read more
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.
Read the 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
- Being tested
- Atezolizumab 1200 mg in 20 ML Injection, Inavolisib, Ipatasertib, Olaparib, Sacituzumab govitecan
- Keywords
- Breast Cancer, Post-neoadjuvant therapy, genomics-guided, molecular diagnostic, targeted therapy, high risk
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atezolizumab 1200 mg in 20 ML InjectionDrug
Also called Tecentriq
Arm 1
InavolisibDrug
Arm 2
IpatasertibDrug
Arm 3
OlaparibDrug
Also called Lynparza
Arm 4
Sacituzumab govitecanDrug
Also called Trodelvy
Arm 5
Trastuzumab/pertuzumabDrug
Also called Phesgo
Arm 6
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 Atezolizumab (Immune Evasion) | Experimental | Atezolizumab Dosage: 1200 mg, intravenous, on d1, q21d Receives: Drug: Atezolizumab 1200 mg in 20 ML Injection |
| Arm 2 Inavolisib (PI3K) | Experimental | Inavolisib Dosage: 9 mg, oral, on d1-d28, q28d Receives: Drug: Inavolisib |
| Arm 3 Ipatasertib (AKT) | Experimental | Ipatasertib Dosage: 400 mg, oral, on d1-d21, q28d Receives: Drug: Ipatasertib |
| Arm 4 Olaparib (PARP, DNA-Repair) | Experimental | Olaparib Dosage: 300 mg, oral, bid d1-d28, q28d Receives: Drug: Olaparib |
| Arm 5 Sacituzumab Govitecan (TROP-2) | Experimental | Sacituzumab Govitecan Dosage: 10 mg/kg BW, intravenous, on d1 and d8, q21d Receives: Drug: Sacituzumab govitecan |
| Arm 6 Trastuzumab/Pertuzumab (ERBBB) | Experimental | Trastuzumab/Pertuzumab Administration: subcutaneous; Initial dose: Trastuzumab 600 mg, Pertuzumab 1200 mg, 30 000 units hyaluronidase; Maintainance dose: Trastuzumab 600 mg, Pertuzumab 600 mg, 20 000 units hyaluronidase; Frequency: on d1, q21d Receives: Drug: Trastuzumab/pertuzumab |
| Arm 7 Observation | No intervention | Observation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Invasive Disease-free Survival (IDFS) as defined by Hudis et al in the entire study population four years after surgery
Primary objective is to improve clinical outcome in early high-risk breast cancer by biomarker-guided post-neoadjuvant therapy (systemic treatment in the adjuvant setting following neoadjuvant therapy, surgery and post-neoadjuvant standard therapy)
Measured: Four years after surgery
Secondary outcomes (4)
Invasive Disease-free Survival (IDFS) as defined by Hudis et al
in each study arm separately
Measured: Four years after surgery
Distant Disease-free Survival (DDFS) as defined by Hudis et al
in each study arm separately and overall
Measured: Four years after surgery
Overall Survival
in each study arm separately and overall
Measured: When the last patient has completed four years after surgery
Incidence of Treatment-Emergent Adverse Events (safety and tolerability)
in each study arm separately and overall
Measured: Through treatment period of the study, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2022
- Study start29 Jun 2023
- Primary completionMar 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early-stage Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Umbrella
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- German Cancer Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andreas Schneeweiss, Prof. Dr., Principal investigator, National Center for Tumor Diseases (NCT)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05332561
- Sponsor's protocol ID
- DKFZ-2019-008
- Other IDs
- 2020-002606-22, 01EK2202A, 2024-514022-23-00
- Status last verified
- Feb 2025
- First submitted
- 22 Mar 2022
- Last updated
- 20 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer - a Multicenter, Open-label, Umbrella Phase-II Study - COGNITION-GUIDE
- ClinicalTrials.gov ID
- NCT05332561
- Acronym / sponsor ID
- DKFZ-2019-008
- Conditions
- Early-stage Breast Cancer
- Keywords
- Breast Cancer, Post-neoadjuvant therapy, genomics-guided, molecular diagnostic, targeted therapy, high risk
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- German Cancer Research CenterUniversity, hospital or other
- Study start
- 29 Jun 2023 (actual)
- Primary completion
- Mar 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 18 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
- Model description
- Umbrella
| Arm | Type | Receives |
|---|---|---|
| Arm 1 Atezolizumab (Immune Evasion) | Experimental | Drug: Atezolizumab 1200 mg in 20 ML InjectionAtezolizumab Dosage: 1200 mg, intravenous, on d1, q21d |
| Arm 2 Inavolisib (PI3K) | Experimental | Drug: InavolisibInavolisib Dosage: 9 mg, oral, on d1-d28, q28d |
| Arm 3 Ipatasertib (AKT) | Experimental | Drug: IpatasertibIpatasertib Dosage: 400 mg, oral, on d1-d21, q28d |
| Arm 4 Olaparib (PARP, DNA-Repair) | Experimental | Drug: OlaparibOlaparib Dosage: 300 mg, oral, bid d1-d28, q28d |
| Arm 5 Sacituzumab Govitecan (TROP-2) | Experimental | Drug: Sacituzumab govitecanSacituzumab Govitecan Dosage: 10 mg/kg BW, intravenous, on d1 and d8, q21d |
| Arm 6 Trastuzumab/Pertuzumab (ERBBB) | Experimental | Drug: Trastuzumab/pertuzumabTrastuzumab/Pertuzumab Administration: subcutaneous; Initial dose: Trastuzumab 600 mg, Pertuzumab 1200 mg, 30 000 units hyaluronidase; Maintainance dose: Trastuzumab 600 mg, Pertuzumab 600 mg, 20 000 units hyaluronidase; Frequency: on d1, q21d |
| Arm 7 Observation | No intervention | –Observation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Provision of written informed consent
- Female and male patients with non-metastatic early (stage I-III) breast cancer aged ≥ 18 years
- Conducted neoadjuvant chemotherapy and surgery as well as conducted standard post-neoadjuvant treatment +/- radiotherapy (standard according to German guidelines except Abemaciclib and Olaparib)
- For patients with initially triple negative (TNBC) or HER2-positive breast cancer:
- For patients with initially hormone receptor positive and HER2-negative breast cancer: Non-pCR and CPS-EG score
Key exclusion criteria (21 listed)
- Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 year
- Concurrent severe, uncontrolled systemic disease that would place patient at undue risk or interfere with planned treatment
- Concurrent participation or previous treatment within 30 days in another interventional clinical trial
- Persistent toxicity (≥ Grade 2 according to NCI CTCAE v5.0 caused by previous cancer therapy, excluding alopecia
- Clinical signs of active infection (> Grade 2 according NCI CTCAE v5.0)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atezolizumab 1200 mg in 20 ML InjectionAlso: TecentriqArm 1 | Drug | Arm 1 Atezolizumab (Immune Evasion) |
| InavolisibArm 2 | Drug | Arm 2 Inavolisib (PI3K) |
| IpatasertibArm 3 | Drug | Arm 3 Ipatasertib (AKT) |
| OlaparibAlso: LynparzaArm 4 | Drug | Arm 4 Olaparib (PARP, DNA-Repair) |
| Sacituzumab govitecanAlso: TrodelvyArm 5 | Drug | Arm 5 Sacituzumab Govitecan (TROP-2) |
| Trastuzumab/pertuzumabAlso: PhesgoArm 6 | Drug | Arm 6 Trastuzumab/Pertuzumab (ERBBB) |
Primary outcome
Invasive Disease-free Survival (IDFS) as defined by Hudis et al in the entire study population four years after surgery
Time frame: Four years after surgery
Primary objective is to improve clinical outcome in early high-risk breast cancer by biomarker-guided post-neoadjuvant therapy (systemic treatment in the adjuvant setting following neoadjuvant therapy, surgery and post-neoadjuvant standard therapy)
4 secondary outcomes
Invasive Disease-free Survival (IDFS) as defined by Hudis et al
Time frame: Four years after surgery
Distant Disease-free Survival (DDFS) as defined by Hudis et al
Time frame: Four years after surgery
Overall Survival
Time frame: When the last patient has completed four years after surgery
Incidence of Treatment-Emergent Adverse Events (safety and tolerability)
Time frame: Through treatment period of the study, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andreas Schneeweiss, Prof. Dr. contact
Richard Schlenk, Prof. Dr. contact
Andreas Schneeweiss, Prof. Dr. principal investigator
National Center for Tumor Diseases (NCT)
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atezolizumab 1200 mg in 20 ML Injection, Inavolisib and Ipatasertib in people with Early-stage Breast Cancer, run by German Cancer Research Center at 9 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andreas Schneeweiss, Prof. Dr. (+49(0)622156 ext. 36051, andreas.schneeweiss@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Invasive Disease-free Survival (IDFS) as defined by Hudis et al in the entire study population four years after surgery (time frame: Four years after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025.