Clinical trial • Phase I/II • Oncology

RGT-419B for Breast cancer | Estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer

Phase I/II trial of RGT-419B for Breast cancer | Estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Breast cancer | Estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer
Trial Stage
Phase I/II
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
05-08-2025
First CTIS Authorization Date
26-11-2025

Trial design

Randomised, open-label, abemaciclib (film-coated tablet) relabeled for clinical trial use; used in combination with giredestrant (dose and schedule not specified in provided record).-controlled, adaptive Phase I/II trial in France, Germany, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Abemaciclib (film-coated tablet) relabeled for clinical trial use; used in combination with giredestrant (dose and schedule not specified in provided record).
Adaptive
True, Phase Ib includes dose‑finding/dose‑escalation elements to evaluate DLTs and identify recommended dose for Phase II; Phase II compares two dose levels of GDC-4198 in combination with giredestrant.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
212

Eligibility

Recruits 212 paediatric patients.

Vulnerable Population
Vulnerable populations selected (isVulnerablePopulationSelected=true). Subject information and informed consent forms are available for Newborn, Infant and Pregnant participants (e.g. L1_GO46021_Newborn-ICF_FR, L1_GO46021_Infant_ICF_ES, L1_GO46021_Pregnant-Participant-ICF_FR), indicating consent/assent processes are addressed in the ICF documents.

Inclusion criteria

  • {"criterion_text":"- Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced (not amenable to surgical or radiation therapy with curative intent) or metastatic"}
  • {"criterion_text":"- Previously documented ER+ tumor according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP; Allison et al. 2020) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines"}
  • {"criterion_text":"- Previously documented HER2– tumor according to ASCO/CAP (Wolff et al. 2023) or ESMO guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines"}
  • {"criterion_text":"- Disease progression during or after treatment with an approved CDK4/6 inhibitor (e.g., abemaciclib, palbociclib, ribociclib, etc.) and endocrine therapy (ET) in the locally advanced or metastatic setting"}
  • {"criterion_text":"- Measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)"}
  • {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1"}

Exclusion criteria

  • {"criterion_text":"- Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term (including massive uncontrolled effusions [pleural, pericardial, peritoneal] or pulmonary lymphangitis) appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines"}
  • {"criterion_text":"- Have received more than one-line of therapy for locally advanced or metastatic disease"}
  • {"criterion_text":"- Have received prior chemotherapy for metastatic breast cancer"}
  • {"criterion_text":"- Treatment with anti-cancer therapies, including investigational therapies, within 28 days or 5 drug elimination half‑lives, whichever is shorter, prior to initiation of study drug"}
  • {"criterion_text":"- Poor peripheral venous access"}
  • {"criterion_text":"- Malabsorption condition (e.g., active inflammatory gastrointestinal (GI) disease, etc.) or other GI conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Incidence and severity of adverse events, with severity determined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE v5.0) grading scale","definition_or_measurement_approach":"Severity determined according to NCI CTCAE v5.0"}
  • {"endpoint_text":"- Change from baseline in selected vital signs","definition_or_measurement_approach":"Change from baseline"}
  • {"endpoint_text":"- Change from baseline in selected clinical laboratory test results","definition_or_measurement_approach":"Change from baseline"}
  • {"endpoint_text":"- Incidence and nature of dose-limiting toxicities (DLTs)","definition_or_measurement_approach":"Incidence and characterization of DLTs as recorded during dose‑limiting evaluation period (DLT definitions not detailed in provided record)"}
  • {"endpoint_text":"- Progression-free survival","definition_or_measurement_approach":"Not specified in the provided record"}

Secondary endpoints

  • {"endpoint_text":"- Phase Ib Stage: Overall Response Rate (ORR)","definition_or_measurement_approach":"ORR (definition/assessment method not further specified in record)"}
  • {"endpoint_text":"- Phase Ib Stage:Clinical Benefit Rate (CBR)","definition_or_measurement_approach":"CBR (definition/assessment method not further specified in record)"}
  • {"endpoint_text":"- Phase Ib Stage:Area under the concentration time-curve from Time 0 to last measurable concentration (AUC0-t), area under the concentration time-curve from Time 0 to infinity (AUCinf), and maximum serum Concentration (Cmax) following administration of a single dose of GDC-4198 under fasted and fed conditions","definition_or_measurement_approach":"Pharmacokinetic parameters AUC0-t, AUCinf, Cmax following single-dose under fed and fasted conditions"}
  • {"endpoint_text":"- Phase II Stage: Overall Response Rate (ORR)","definition_or_measurement_approach":"ORR (definition/assessment method not further specified in record)"}
  • {"endpoint_text":"- Phase II Stage:Duration of Response (DOR)","definition_or_measurement_approach":"DOR (definition/assessment method not further specified in record)"}
  • {"endpoint_text":"- Phase II Stage: Clinical Benefit Rate (CBR)","definition_or_measurement_approach":"CBR (definition/assessment method not further specified in record)"}
  • {"endpoint_text":"- Phase II Stage: Overall Survival (OS)","definition_or_measurement_approach":"OS (definition/assessment method not further specified in record)"}
  • {"endpoint_text":"- Phase II Stage: OS rate at 6 months and 12 months","definition_or_measurement_approach":"OS rate at specified timepoints (6 and 12 months)"}
  • {"endpoint_text":"- Phase II Stage: PFS rate at 6 months and 12 months","definition_or_measurement_approach":"PFS rate at specified timepoints (6 and 12 months)"}
  • {"endpoint_text":"- Phase II Stage:Incidence and severity of adverse events, with severity determined according to the CTCAE v5.0 grading scale","definition_or_measurement_approach":"Severity determined according to CTCAE v5.0"}
  • {"endpoint_text":"- Phase II Stage: Change from baseline in selected vital signs","definition_or_measurement_approach":"Change from baseline"}
  • {"endpoint_text":"- Phase II Stage: Change from baseline in selected clinical laboratory test results","definition_or_measurement_approach":"Change from baseline"}
  • {"endpoint_text":"- Phase II Stage:Plasma concentrations of GDC-4198 and its metabolites at specified timepoints","definition_or_measurement_approach":"Plasma concentration measurements at specified timepoints (PK sampling)"}
  • {"endpoint_text":"- Phase II Stage: Relationship between GDC-4198 dose and safety, pharmacokinetics, and efficacy","definition_or_measurement_approach":"Dose–response relationship assessments across safety, PK and efficacy endpoints"}

Recruitment

Planned Sample Size
212
Recruitment Window Months
32
Consent Approach
Subject information and informed consent forms are provided; ICFs available in multiple languages (French, German, Italian, Spanish) and include specific ICFs for newborn, infant and pregnant participants (e.g. L1_GO46021_Newborn-ICF_FR, L1_GO46021_Infant_ICF_ES, L1_GO46021_Pregnant-Participant-ICF_FR), indicating age-specific documents are prepared and consent processes are addressed in the ICFs.

Geography

Total Number Of Sites
23
Total Number Of Participants
73

France

Earliest CTIS Part Ii Submission Date
17-10-2025
Latest Decision Or Authorization Date
26-11-2025
Processing Time Days
40
Number Of Sites
5
Number Of Participants
16

Sites

Site Name
Institut Gustave Roussy
Department Name
Medical Oncology Department
Principal Investigator Name
Chayma Bousrih
Principal Investigator Email
Chayma.bousrih@gustaveroussy.fr
Contact Person Name
Chayma Bousrih
Site Name
Centre Oscar Lambret
Department Name
Medical Oncology Department
Principal Investigator Name
Sarra Lakhdar
Principal Investigator Email
s-lakhdar@o-lambret.fr
Contact Person Name
Sarra Lakhdar
Contact Person Email
s-lakhdar@o-lambret.fr
Site Name
Centre Francois Baclesse
Department Name
Medical Oncology Department
Principal Investigator Name
George Emile
Principal Investigator Email
g.emile@baclesse.unicancer.fr
Contact Person Name
George Emile
Contact Person Email
g.emile@baclesse.unicancer.fr
Site Name
Institut Godinot
Department Name
Medical Oncology Department
Principal Investigator Name
Pauline Soibinet
Principal Investigator Email
Pauline.soibinet@reims.unicancer.fr
Contact Person Name
Pauline Soibinet
Site Name
Centre De Lutte Contre Le Cancer Eugene Marquis
Department Name
Medical Oncology Department
Principal Investigator Name
Fanny Le Du
Principal Investigator Email
f.ledu@rennes.unicancer.fr
Contact Person Name
Fanny Le Du
Contact Person Email
f.ledu@rennes.unicancer.fr

Germany

Earliest CTIS Part Ii Submission Date
10-11-2025
Latest Decision Or Authorization Date
26-11-2025
Processing Time Days
16
Number Of Sites
6
Number Of Participants
17

Sites

Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Department für Frauengesundheit
Principal Investigator Name
Léa Louise Volmer
Principal Investigator Email
Lea-Louise.Volmer@med.uni-tuebingen.de
Contact Person Name
Léa Louise Volmer
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Universitäres Brustzentrum, Klinik und Poliklinik für Gynäkologie/ Klinische Studien
Principal Investigator Name
Volkmar Müller
Principal Investigator Email
v.mueller@uke.de
Contact Person Name
Volkmar Müller
Contact Person Email
v.mueller@uke.de
Site Name
Medizinische Hochschule Hannover
Department Name
Klinik für Frauenheilkunde und Geburtshilfe
Principal Investigator Name
Tjoung-Won Park-Simon
Principal Investigator Email
Park-Simon.Tjoung-Won@mh-hannover.de
Contact Person Name
Tjoung-Won Park-Simon
Site Name
KEM I Evang. Kliniken Essen-Mitte gGmbH
Department Name
Interdisziplinäres Brustzentrum
Principal Investigator Name
Sherko Kümmel
Principal Investigator Email
s.kuemmel@kem-med.com
Contact Person Name
Sherko Kümmel
Contact Person Email
s.kuemmel@kem-med.com
Site Name
National Center For Tumor Diseases (NCT) Heidelberg
Department Name
Gynäkologische Onkologie
Principal Investigator Name
Carlo Fremd
Principal Investigator Email
Carlo.Fremd@med.uni-heidelberg.de
Contact Person Name
Carlo Fremd
Site Name
Technische Universitaet Dresden
Department Name
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
Principal Investigator Name
Pauline Wimberger
Principal Investigator Email
pauline.wimberger@ukdd.de
Contact Person Name
Pauline Wimberger
Contact Person Email
pauline.wimberger@ukdd.de

Italy

Earliest CTIS Part Ii Submission Date
31-10-2025
Latest Decision Or Authorization Date
26-11-2025
Processing Time Days
26
Number Of Sites
5
Number Of Participants
19

Sites

Site Name
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
Department Name
Onco-Ematology, SC ONCOLOGY
Principal Investigator Name
Alberto Zambelli
Principal Investigator Email
azambelli@asst-pg23.it
Contact Person Name
Alberto Zambelli
Contact Person Email
azambelli@asst-pg23.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Oncologia Medica
Principal Investigator Name
Antonino Musolino
Principal Investigator Email
antonino.musolino@irst.emr.it
Contact Person Name
Antonino Musolino
Contact Person Email
antonino.musolino@irst.emr.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Medical Oncology and Haematology
Principal Investigator Name
Claudio Zamagni
Principal Investigator Email
claudio.zamagni@aosp.bo.it
Contact Person Name
Claudio Zamagni
Contact Person Email
claudio.zamagni@aosp.bo.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Medical Oncology Unit
Principal Investigator Name
Giampaolo Bianchini
Principal Investigator Email
bianchini.giampaolo@hsr.it
Contact Person Name
Giampaolo Bianchini
Contact Person Email
bianchini.giampaolo@hsr.it
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
U.O. di Oncologia Medica - Breast unit
Principal Investigator Name
Rebecca Pedersini
Principal Investigator Email
rebecca.pedersini@gmail.com
Contact Person Name
Rebecca Pedersini
Contact Person Email
rebecca.pedersini@gmail.com

Spain

Earliest CTIS Part Ii Submission Date
03-11-2025
Latest Decision Or Authorization Date
26-11-2025
Processing Time Days
23
Number Of Sites
7
Number Of Participants
21

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Medical Oncology
Principal Investigator Name
Eva María Ciruelos Gil
Principal Investigator Email
eva.ciruelos@gmail.com
Contact Person Name
Eva María Ciruelos Gil
Contact Person Email
eva.ciruelos@gmail.com
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Medical Oncology
Principal Investigator Name
Isabel Echavarria Diaz-Guardamino
Principal Investigator Email
isabel.echavarria@salud.madrid.org
Contact Person Name
Isabel Echavarria Diaz-Guardamino
Site Name
Institut Catala D'oncologia
Department Name
Medical Oncology
Principal Investigator Name
Rafael Villanueva Vazquez
Principal Investigator Email
ravillanueva@iconcologia.net
Contact Person Name
Rafael Villanueva Vazquez
Contact Person Email
ravillanueva@iconcologia.net
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Medical Oncology
Principal Investigator Name
Begoña Bermejo de las Heras
Principal Investigator Email
begobermejo@gmail.com
Contact Person Name
Begoña Bermejo de las Heras
Contact Person Email
begobermejo@gmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncology
Principal Investigator Name
Meritxell Bellet Ezquerra
Principal Investigator Email
mbellet@vhio.net
Contact Person Name
Meritxell Bellet Ezquerra
Contact Person Email
mbellet@vhio.net
Site Name
Hospital Beata Maria Ana
Department Name
Medical Oncology
Principal Investigator Name
Javier Cortes Castan
Principal Investigator Email
javier.cortes@maj3.health
Contact Person Name
Javier Cortes Castan
Contact Person Email
javier.cortes@maj3.health
Site Name
Hospital Beata Maria Ana (duplicate entry name in record)
Department Name
Medical Oncology
Principal Investigator Name
Javier Cortes Castan
Principal Investigator Email
javier.cortes@maj3.health
Contact Person Name
Javier Cortes Castan
Contact Person Email
javier.cortes@maj3.health

Sponsor

Primary sponsor

Full Name
Genentech Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
PPD Development LP
Responsibilities
Site management
Name
Eresearchtechnology Inc.
Responsibilities
Other Third Party Duty
Name
Bioclinica Inc.
Responsibilities
Other Third Party Duty
Name
4g Clinical LLC
Responsibilities
3

Third parties

  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Other Third Party Duty","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Other Third Party Duty","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Site management","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Other Third Party Duty","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
RO7840734
Active Substance
RGT-419B
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Investigational Product Name
RO7197597
Active Substance
GIREDESTRANT
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Investigational Product Name
ABEMACICLIB
Active Substance
ABEMACICLIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Combination Treatment
Yes

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