Adjuvant Therapy With Abemaciclib + SOC ET vs. SOC ET in Clinical or Genomic High Risk, HR+/HER2- EBC

Phase 3

Recruiting

• Conditions: Breast Cancer Female
• Interventions: Drug: Abemaciclib 50 MG; 150mg 1-0-1 per os

• Registration Number: NCT04565054
• Lead Sponsor: West German Study Group

Brief Summary

Patients with breast cancer, who have completed first line therapy (e.g., radiotherapy, chemotherapy, surgery), and who have to be identified with having a high risk of recurrence of cancer, will be eligible for the study. This patient group is currently offered a standard of care chemotherapy plus endocrine therapy (ET). The study investigates whether the patient group with high-risk early breast cancer benefits from treatment with the medication abemaciclib in combination with ET compared to ET alone.

Detailed Description

The WSG ADAPT trial program is one of the first new generation trials addressing the issue of individualization of (neo)-adjuvant decision-making in early breast cancer (EBC) in a subtype-specific manner. The first WSG ADAPT umbrella trial (NCT01779206) aimed to establish early predictive molecular surrogate markers for response after a short 3-week induction treatment.

The goals of the WSG ADAPT trial program - early response assessment and subtype-specific therapy tailoring to those patients who are most likely to benefit - have contributed to the positive national and international feedback regarding the ADAPT-concept as a whole.

The aim of this ADAPTlate phase-III-trial is to gain further knowledge of the group of patients at intermediate to high risk for disease recurrence, who have completed definite locoregional therapy (with or without neoadjuvant or adjuvant chemotherapy). With ADAPTlate it is planned to investigate if the intermediate to high-risk patient group identified during the screening phase derives additional benefit from treatment with abemaciclib in combination with ET compared to ET alone.

Study Timeline

• Study First Submitted: 2020-07-07
• Study Start: 2020-09-02
• Study First Submitted QC: 2020-09-24
• Study First Posted: 2020-09-25
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-10
• Primary Completion: 2028-06
• Study Completion: 2029-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 1260

Inclusion Criteria

A. Prior to REGISTRATION

1. Written informed consent prior to any study procedures (outcomes of standard-of-care procedures performed before signing of informed consent by the patient but within allowed screening period can be used for screening of patient). 2. Female. 3. ≥ 18 years of age. 4a. EITHER: (Post)menopausal status at the time of initiation of adjuvant study medication

• patient underwent bilateral oophorectomy, or

• age ≥ 60, or

• age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, or ovarian suppression) and/or FSH and estradiol in the postmenopausal range per local normal range.

  4b. OR: Pre-/perimenopausal patients:

• confirmed negative serum or urine pregnancy test (β-hCG) before starting study treatment, or

• patient has had a hysterectomy. 5. Histologically confirmed diagnosis(by local laboratory ) of estrogen-receptor positive and/or progesterone-receptor positive (>1% ) primary early breast cancer or local relapse. In case the receptor status from local pathology is unclear a central pathology review is obligatory. Results must be known prior to randomization.

  6. Patient has HER2-negative breast cancer defined as

• a negative in-situ hybridization test or an IHC status of 0, 1+, or 2+,

• if IHC is 2+, a negative in-situ hybridization (FISH, CISH, or SISH) test is required (based on the analyzed tissue sample at initial diagnosis by a local laboratory).

  7. Patients are eligible

• with completed (i.e., 5 years according to SoC), planned or ongoing adjuvant endocrine therapy, without any signs of distant relapse or secondary malignancy AND

• if primary diagnosis was 6 years or less before enrollment 8a. Intermediate to high clinical or genomic risk, defined as either one of the following criteria:

• c or p or ypN 2-3 with/without (neo)adjuvant chemotherapy;

• in patients with c/ypN0-1:

• non-pCR in patients with G3 or c/ypN1

• high biological risk defined as G3 with Ki-67 ≥40%

• or high genomic risk (RS>25 (known or Oncotype Dx® in screening phase) or another test)

• high CTS5 score or UICC stage IIb (clinical if neoadjuvant chemotherapy or pathological)

OR, if patients do not fulfill above criteria:

• patients ≤50 years old or pre-/perimenopausal and c or (y)pN1 disease (in particular if ET-non-response or no chemotherapy)
• patients >50 years old and postmenopausal and c or (y)pN1 with intermediate genomic risk (RS≥18) or non-low risk by another test

ET non-response definition:

Ki-67 post-treatment > 10% (central or local pathology value) OR 8b. Patients after isolated locoregional relapse with high-risk patterns (e.g., rpT2-3 or rpN1-3 or G3 or Ki-67 pre-treatment ≥20%), once surgery with free margins was completed Note: Inclusion is only possible for the first locoregional relapse removed by surgery (free margins) OR 8c. Patients with any high clinical risk at Investigator´s assessment but not fulfilling above criteria: consultation with sponsor required

B. Prior to RANDOMIZATION in the study 9. Completed primary therapy of breast cancer according to current guidelines, i.e., after (neo)adjuvant treatment, definite surgery and radiotherapy, if applicable.

10. No clinical evidence of distant metastasis (confirmation recommended prior to randomization by either combination of or either one of the following examinations: CT thorax / abdomen, chest X-ray, liver ultrasound, bone scan, PET-CT). 11. Patient has available tumor tissue from primary diagnostic biopsy. 12. No contraindication for adjuvant ET. 13. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 14. Patient has adequate bone marrow and organ function as defined by the following laboratory values:

• absolute neutrophil count ≥ 1.5 × 109/L,

• platelets ≥ 100 × 109/L,

• hemoglobin ≥ 8.0 g/dL,

• total bilirubin ≤ 1.5 ULN, except for patients with Gilbert's Syndrome who may only be included if the total bilirubin is ≤ 2.0 × ULN or direct bilirubin within normal ranges,

• aspartate transaminase (AST) ≤ 3 × ULN,

• alanine transaminase (ALT) ≤ 3 × ULN,

• serum creatinine ≤ 1.5 x ULN. 15. Ability to swallow abemaciclib tablets or to administer other study medication, respectively.

  16. Ability to communicate with the investigator and comply with study procedures.

  17. Willing to receive therapy by clinical site, as required by the protocol.

Exclusion Criteria

Patients eligible for inclusion in this study must not meet any of the following criteria:

1. Patient with distant metastases of breast cancer beyond regional lymph nodes.

2. Previously received CDK 4/6 inhibitor.

3. Patient with a known hypersensitivity to any of the excipients of abemaciclib or standard-of-care endocrine therapy.

4. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.

5. Patient has not recovered from clinical and laboratory acute toxicities related to prior anticancer therapies to NCI CTCAE version 5.0 Grade ≤ 1 (polyneuropathy ≤ 2 is allowed).

6. Patient has a concurrent malignancy or non-breast malignancy within 5 years prior to randomization.

7. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small-bowel resection).

8. Patient has any active systemic bacterial infection (requiring intravenous antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.

9. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator´s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study, or compromise compliance with the protocol (e.g., interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea, etc.).

10. Patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

11. Patient is currently receiving any of the following substances, which cannot be discontinued 7 days prior to day 1 of study treatment:

    o concomitant medications and herbal supplements, that are strong inducers or inhibitors of CYP3A4.

12. Participation in a prior investigational study within 30 days prior to enrollment.

13. Not able to understand and to comply with study instructions and requirements.

14. Pregnant or nursing (lactating) woman.

15. Woman of child-bearing potential defined as woman physiologically capable of becoming pregnant, unless she is using highly effective methods of contraception during the study treatment and for 21 days after stopping the treatment:

    1. total abstinence (when this is in line with the preferred and usual lifestyle of the patient).
    2. female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment.
    3. male partner sterilization (at least 6 months prior to study screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.
    4. placement of an intrauterine device (IUD).
    5. use of condom + spermicide.

16. Use of oral (estrogen and progesterone), transdermal, injected, or implanted hormonal methods of contraception as well as hormonal replacement therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Abemaciclib plus ET	Abemaciclib 50 MG; 150mg 1-0-1 per os	Abemaciclib 150 mg, 2 x daily, resulting in 300 mg/day, oral, 24 months plus endocrine treatment of physician´s choice

Primary Outcome Measures

Name	Time	Method
invasive disease-free survival (iDFS)	at end of study, 3-6 years after start of study treatment	superiority in invasive disease-free survival (iDFS) of abemaciclib + endocrine therapy vs. standard-of-care endocrine therapy in patients with HR+/HER2- high risk breast cancer.

Secondary Outcome Measures

Name	Time	Method
differences in overall survival (OS) and dDFS	at end of study, 3-6 years after start of study treatment	differences in overall survival (OS) and dDFS between arms
subgroup and multivariable survival analyses	at end of study, 3-6 years after start of study treatment	subgroup and multivariable survival analyses
EQ-5D-5L	at end of study, on average 3-6 years after start of treatment	quality of life (QoL)
EORTC QLQ-C30	at end of study, on average 3-6 years after start of treatment	quality of life (QoL)
CNS metastases	at end of study, 3-6 years after start of study treatment	occurrence of CNS metastases
overall survival (OS)	at end of study, 3-6 years after start of treatment	assessment of overall survival (OS) and distant DFS (dDFS) in both arms
EORTC QLQ-BR23	at end of study, on average 3-6 years after start of treatment	quality of life (QoL)

Trial Locations

Locations (67)

Praxis für interdisziplinäre Onkologie & Hämatologie; 🇩🇪 Freiburg, Baden-Württemberg, Germany

SLK Kliniken Heilbronn Klinik für Gynäkologie und Geburtshilfe; 🇩🇪 Heilbronn, Baden-Württemberg, Germany

Studienzentrum Onkologie Ravensburg Prof. Dr. Dechow, Prof. Dr. Decker, Dr. Nonnenbroich GbR; 🇩🇪 Ravensburg, Baden-Württemberg, Germany

Universitätsklinikum Ulm Frauenheilkunde, Geburtshilfe; 🇩🇪 Ulm, Baden-Württemberg, Germany

GRN-Klinik Weinheim Gynäkologie und Geburtshilfe; 🇩🇪 Weinheim, Baden-Württemberg, Germany

Universitätsklinikum Tübingen Department für Frauengesundheit, Brustzentrum; 🇩🇪 Tübingen, Baden-Wüttenburg, Germany

Gemeinschaftspraxis Dr. Heinrich, Prof. Dr. Bangerter; 🇩🇪 Augsburg, Bavaria, Germany

Medizinisches Zentrum für Hämatologie und Onkologie München MVZ GmbH; 🇩🇪 Munich, Bavaria, Germany

Hämatologisch-Onkologische Schwerpunktpraxis Würzburg GbR Dr. Schöttker/ Dr. Pretscher; 🇩🇪 Würzburg, Bavaria, Germany

Klinikum der Universität München Campus Großhadern Frauenheilunde und Geburtsklinik; 🇩🇪 Muenchen, Bayern, Germany

Rotkreuzkliniken München, Interdisziplinbäres Brustzentrum; 🇩🇪 München, Bayern, Germany

Medizinische Universität Lausitz - Carl-Thiem Frauenklinik; 🇩🇪 Cottbus, Brandenburg, Germany

Klinikum Ernst von Bergmann gGmbH Brustzentrum; 🇩🇪 Potsdam, Brandenburg, Germany

St. Josefs-Hospital Wiesbaden GmbH Ambulanz der Frauenklinik, Brustzentrum; 🇩🇪 Wiesbaden, Hessen, Germany

Onco Medical Consult GmbH; 🇩🇪 Frankfurt a.M., Hesse, Germany

Gemeinschaftspraxis für Hämatologie und Onkologie; 🇩🇪 Langen, Hesse, Germany

Studien GbR Braunschweig Dr. Lorenz/Dr. Kreiss-Sender; 🇩🇪 Braunschweig, Lower Saxony, Germany

ÜBAG MVZ Onkologische Kooperation Harz; 🇩🇪 Goslar, Lower Saxony, Germany

Medizinische Hochschule Hannover Frauenheilkunde; 🇩🇪 Hannover, Lower Saxony, Germany

Onkologie UnterEms Leer-Emden-Papenburg Dr. L. Müller; 🇩🇪 Leer, Lower Saxony, Germany

Pius-Hospital Oldenburg Hämatologie, Onkologie; 🇩🇪 Oldenburg, Lower Saxony, Germany

Klinikum Südstadt Rostock Frauenklinik; 🇩🇪 Rostock, Mecklenburg-Vorpommern, Germany

MVZ II der Niels Stensen Kliniken Onkologie u. Hämatologie; 🇩🇪 Georgsmarienhütte, Niedersachsen, Germany

Diakovere Henriettenstift Frauenklinik; 🇩🇪 Hannover, Niedersachsen, Germany

Kliniken der Stadt Köln Krankenhaus Köln-Holweide Medizinische Klinik Brustzentrum; 🇩🇪 Köln, Nordrhein-Westfalen, Germany

Marienhospital GmbH Studienzentrale Brustcentrum Aachen-Kreis Heinsberg; 🇩🇪 Aachen, NRW, Germany

Uniklinik RWTH Aachen Gynäkologie und Geburtsmedizin; 🇩🇪 Aachen, NRW, Germany

Evangelisches Krankenhaus Bergisch Gladbach gGmbH Brustzentrum,; 🇩🇪 Bergisch Gladbach, NRW, Germany

Universitätsklinikum Düsseldorf Frauenheilkunde und Geburtshilfe; 🇩🇪 Düsseldorf, NRW, Germany

Luisenkrankenhaus Brustzentrum; 🇩🇪 Düsseldorf, NRW, Germany

Zentrum für ambulante gynäkologisch Onkologie - ZAGO Haus 03; 🇩🇪 Krefeld, NRW, Germany

Christliches Klinikum Unna Mitte Gynäkologie und Geburtshilfe; 🇩🇪 Unna, NRW, Germany

Marien Hospital Witten Brustzentrum; 🇩🇪 Witten, NRW, Germany

Helios Klinikum Wuppertal Landesfrauenklinik; 🇩🇪 Wuppertal, NRW, Germany

Onkologische Schwerpunktpraxis Bielefeld; 🇩🇪 Bielefeld, NRW, Germany

St.-Antonius-Hospital Eschweiler Hämatologie/Onkologie; 🇩🇪 Eschweiler, NRW, Germany

Universitätsklinikum Essen Frauenheilkunde und Geburtshilfe; 🇩🇪 Essen, NRW, Germany

Gynäkologisches Zentrum Bonn PD Dr. med. Christian Kurbacher; 🇩🇪 Bonn, NRW, Germany

GYNONOVA GbR Schwerpunktpraxis für gynäkologische Onkologie; 🇩🇪 Cologne, NRW, Germany

Onkologische Schwerpunktpraxis; 🇩🇪 Gütersloh, NRW, Germany

St. Elisabeth-Krankenhaus GmbH, Brustzentrum - Senologie; 🇩🇪 Köln, NRW, Germany

Städtisches Klinikum Lüneburg Frauenklinik; 🇩🇪 Lüneburg, NRW, Germany

Johannes Wesling Klinikum Minden Innere Medizin, Hämatologie, Onkologie; 🇩🇪 Minden, NRW, Germany

Brustzentrum Niederrhein, im ev. Krankenhaus Bethesda; 🇩🇪 Moenchengladbach, NRW, Germany

Universitätsklinikum Münster Brustzentrum; 🇩🇪 Münster, NRW, Germany

Marien Krankenhaus Schwerte MKS St. Paulus GmbH; 🇩🇪 Schwerte, NRW, Germany

Kliniken Essen-Mitte, Klinik für Senologie/Interdisziplinäres Brustzentrum; 🇩🇪 Essen, NRW, Germany

Praxisgemeinschaft Gynäkologische Onkologie & Spezielle Operative Gynäkologie; 🇩🇪 Hildesheim, NRW, Germany

Klinikum Mutterhaus der Borromäerinnen Innere Medizin 1; 🇩🇪 Trier, Rheinland-Pfalz, Germany

Praxisklinik für Hämatologie und Onkologie Koblenz; 🇩🇪 Koblenz, Rhineland-Palatinate, Germany

Universitätsklinikum des Saarlandes Klinik für Frauenheilkunde; 🇩🇪 Homburg (Saar), Saarland, Germany

Klinikum Obergöltzsch Brustzentrum Vogtland; 🇩🇪 Rodewisch, Sachsen, Germany

Universitätsklinikum Halle (UKH), Universitätsklinik und Poliklinik für Gynäkologie; 🇩🇪 Halle (Saale), Saxony Anhalt, Germany

Klinikum Magdeburg Frauenheilkunde und Geburtshilfe; 🇩🇪 Magdeburg, Saxony-Anhalt, Germany

Johanniter Krankenhaus Frauenklinik; 🇩🇪 Stendal, Saxony-Anhalt, Germany

Klinikum Chemnitz Frauenheilkunde und Geburtshilfe; 🇩🇪 Chemnitz, Saxony, Germany

Onkozentrum Dresden/Freiberg; 🇩🇪 Dresden, Saxony, Germany

Onkologische Gemeinschaftspraxis; 🇩🇪 Dresden, Saxony, Germany

Klinikum St. Georg Gynäkologie und Geburtshilfe; 🇩🇪 Leipzig, Saxony, Germany

MediOnko-Institut GbR; 🇩🇪 Berlin, Germany

Praxis für gynäkologische Onkologie im Brustzentrum City am Sankt Gertrauden KH; 🇩🇪 Berlin, Germany

DRK Kliniken Berlin Köpenick Brustzentrum im Onkozentrum; 🇩🇪 Berlin, Germany

Onkologisch-Hämatologische Schwerpunktpraxis; 🇩🇪 Bremen, Germany

AGAPLESION Diakonie-Klinikum Hamburg Gyn. Studienambulanz; 🇩🇪 Hamburg, Germany

Mammazentrum Hamburg MVZ GbR; 🇩🇪 Hamburg, Germany

Brustzentrum, Elisabeth-Krankenhaus gGmbH; 🇩🇪 Kassel, Germany

Caritas Traegergesellschaft Saarbruecken mbH (CTS) Frauenklinik; 🇩🇪 Saarbrücken, Germany