A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1)

NCT03988036 | Completed Phase 2 DMC

• 2 other identifiers: WSG-AM092018-003996-37
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 12

Brief Summary

Keyriched-1 is a multicenter, interventional, prospective, single arm, open label, neoadjuvant phase II trial evaluating the pathological complete response (pCR) rate induced by pembrolizumab in combination with the dual anti-HER2 blockade consisting of trastuzumab biosimilar ABP 980 and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype tested by PAM50.

Conditions

Breast Cancer

Keywords

HR positive; HER2 negative; Early breast cancer; Neoadjuvant; Anti-HER2 therapy; Pertuzumab; Trastuzumab; Pembrolizumab; Immune checkpoint inhibitor; PD-1; PDL-1; PAM50; Phase 2

Outcome Measures

Primary Outcomes (1)

• Evaluation of the pCR rate of the combination therapy consisting of pembrolizumab in combination with the dual anti-HER2 blockade trastuzumab biosimilar ABP 980 and pertuzumab in patients with HER2-enriched early breast cancer assessed by PAM50 testing

  pCR defined as no invasive tumor in breast and lymph nodes (ypT0/is, ypN0) at surgery after study treatment

  After neoadjuvant treatment (planned duration of treatment is 12 weeks)

Secondary Outcomes (9)

• Number and percentage of fatal adverse events as assessed by CTCAE 5.0

  9 months for individual participants

• Number and percentage of serious treatment-emergent adverse events as assessed by CTCAE 5.0

  9 months for individual participants

• Number and percentage of treatment-related adverse events as assessed by CTCAE 5.0

  9 months for individual participants

• Number and percentage of treatment-emergent adverse events of interest as assessed by CTCAE 5.0

  9 months for individual participants

• Number and percentage of adverse events leading to investigational product discontinuation

  9 months for individual participants

Study Arms (1)

HER2-enriched

EXPERIMENTAL

Trial treatment is defined as neoadjuvant therapy only. The Investigational Medicinal Products (IMPs) are pembrolizumab, trastuzumab biosimilar and pertuzumab. * Trastuzumab Biosimilar (Trazimera®) - Investigational Medicinal Product * Loading dose: 8 mg/kg bodyweight at initial administration infusion over 90 min; monitor patient for at least 6 h afterwards. * Maintenance dose: 6 mg/kg bodyweight, over 30-90 min; monitor patient for 2 h afterwards. * Route: Intravenous infusion. * Schedule: Every 3 weeks during the neoadjuvant phase. * Pertuzumab (Perjeta®) - Investigational Medicinal Product * Loading dose: 840 mg, initial administration. * Maintenance dose: 420 mg. * Route: Intravenous infusion. * Schedule: Every 3 weeks during the neoadjuvant phase. * Pembrolizumab (Keytruda®) - Investigational Medicinal Product * Dose: 200 mg. * Route: Intravenous infusion. * Schedule: Every 3 weeks during the neoadjuvant phase.

Drug: Pembrolizumab; Drug: Trastuzumab Biosimilar ABP 980; Drug: Pertuzumab

Interventions

Pembrolizumab DRUG

Intravenous infusion; 200 mg; every 3 weeks

Also known as: Keytruda®

HER2-enriched

Trastuzumab Biosimilar ABP 980 DRUG

Intravenous infusion; 8 mg/kg loading dose, thereafter 6 mg/kg; every 3 weeks

Also known as: Trazimera®

HER2-enriched

Pertuzumab DRUG

Intravenous infusion; 840 mg/kg loading dose, thereafter 420 mg/kg; every 3 weeks

Also known as: Perjeta®

HER2-enriched

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participants, who are at least 18 years of age on the day of signing informed consent with newly histologically locally confirmed diagnosis of HER2neu 2+ or 3+ breast cancer.
• Have previously untreated, non-metastatic (M0) HER2-enriched breast cancer defined as the following combined primary tumor (T) and regional lymph node (N) staging per American Joint Committee on Cancer (AJCC) for breast cancer staging criteria version 7 as assessed by the Investigator based on radiological and/or clinical assessment:
• T1c, N0-N2; T2, N0-N2; T3, N0-N2
• Patients with HER2-enriched, estrogen and/ or progesterone receptor positive or negative breast cancer defined by American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines can be included.
• Availability of tumor imaging performed within three months prior to start of screening phase: breast ultrasound and computed tomography (CT) thorax/abdomen or chest X-ray/liver ultrasound, bone scan, mammography or breast magnetic resonance imaging (MRI) (according to local standard).
• Ability to provide archived tumor tissue sample or at least two newly obtained separate tumor cores from the primary tumor or excisional biopsy of a tumor lesion not previously irradiated at screening to the central laboratory. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred over slides. Newly obtained biopsies are preferred over archived tissue.
• Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
• Patients are eligible to be included in the trial only if all of the following criteria apply \[items 1-6 must be met by the patient to be enrolled into the trial and before the start of the screening phase\]:
• Female patients, who are at least 18 years of age on the day of signing informed consent, with newly histologically locally confirmed diagnosis of HER2neu 2+ or 3+ breast cancer.
• Previously untreated, non-metastatic (M0) HER2-enriched breast cancer defined as the following combined primary tumor (T) and regional lymph node (N) staging per AJCC for breast cancer staging criteria version 7 as assessed by the investigator based on radiological and/or clinical assessment:
• T1c, N0-N2;
• T2, N0-N2;
• T3, N0-N2.
• Patients with HER2-enriched, estrogen and/or progesterone receptor-positive or -negative breast cancer defined by ASCO/CAP guidelines.
• Availability of tumor imaging performed within three months prior to start of screening phase: breast ultrasound and CT thorax/abdomen or chest X-ray/liver ultrasound, bone scan, mammography or breast MRI (according to local standard).

You may not qualify if:

• Patients are excluded from the trial if any of the following criteria apply:
• Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g. CTLA-4, OX 40, CD137) or has participated in MK-3475 clinical trials.
• Patient has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to first dose of study medication.
• Note: Patients must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Patients with ≤Grade 2 neuropathy may be eligible.
• Note: If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Patient has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
• Patient is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Patients who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. Patient should be excluded if she received an investigational agent with anti-cancer or anti-proliferative intent within the last 12 months.
• Patient has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Prior malignancy with a disease-free survival of ≤5 years before signing informed consent.
• Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Patient has a known hypersensitivity to the components of the study therapy, its analogs, murine proteins or any of the excipients.
• Patient has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Patient has a significant cardiovascular disease, such as:
• LVEF \<55%

Sponsors & Collaborators

• West German Study Group: lead
• Merck Sharp & Dohme LLC: collaborator
• NanoString Technologies, Inc.: collaborator

Study Sites (12)

Universitätsklinikum Tübingen Frauenklinik

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Breast Center of the University of Munich (LMU) Universitätsfrauenklinik Großhadern

Munich, Bavaria, 80377, Germany

Location

Rotkreuzklinikum München GmbH Frauenklinik

Munich, Bavaria, 80637, Germany

Location

Niels-Stensen-Kliniken Franziskus-Hospital Harderberg Zentrum für Frauenheilkunde und Abteilung für Senologie

Georgsmarienhütte, Lower Saxony, 49124, Germany

Location

Diakoniekrankenhaus Henriettenstiftung GmbH

Hanover, Lower Saxony, 30559, Germany

Location

Onkologische Praxis

Bielefeld, North Rhine-Westphalia, 33604, Germany

Location

St. Elisabeth Krankenhaus GmbH Brustzentrum

Cologne, North Rhine-Westphalia, 50935, Germany

Location

Onkodok GmbH

Gütersloh, North Rhine-Westphalia, 33332, Germany

Location

Ev. Krankenhaus Bethesda Brustzentrum Niederrhein

Mönchengladbach, North Rhine-Westphalia, 41061, Germany

Location

Praxisnetzwerk

Troisdorf, North Rhine-Westphalia, 53840, Germany

Location

Charité Campus Mitte Klinik für Gynäkologie

Berlin, 10117, Germany

Location

Mammazentrum Hamburg

Hamburg, 20357, Germany

Location

Related Publications (1)

• Kuemmel S, Graeser M, Schmid P, Reinisch M, Feuerhake F, Volk V, Armeanu-Ebinger S, Schutz L, Kelemen O, Schroeder C, Ossowski S, Jozwiak K, Kostara A, Scheffen I, Ludtke-Heckenkamp K, Hilpert F, Kentsch A, Ziske C, Depenbusch R, Braun M, Blohmer JU, Zu Eulenburg C, Christgen M, Bartels S, Kreipe HH, Wuerstlein R, Biehl C, Pelz E, Hartkopf A, Harbeck N, Gluz O; West German Study Group investigators. Chemotherapy-free neoadjuvant pembrolizumab combined with trastuzumab and pertuzumab in HER2-enriched early breast cancer (WSG-KEYRICHED-1): a single-arm, phase 2 trial. Lancet Oncol. 2025 May;26(5):629-640. doi: 10.1016/S1470-2045(25)00097-X.

  PMID: 40318646 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• s.kuemmel@kem-med.com Kuemmel, Professor

  Clinics Essen-Mitte, Breast Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A multicenter, interventional, prospective, single arm, open label, neoadjuvant phase II trial evaluating the pathological complete response (pCR) rate induced by pembrolizumab in combination with the dual anti-HER2 blockade consisting of trastuzumab biosimilar and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype tested by PAM50.

Study Record Dates

• First Submitted: March 7, 2019
• First Posted: June 17, 2019
• Study Start: August 18, 2020
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: May 15, 2023

Record last verified: 2023-05

Locations

DE (12)