Une étude visant à en apprendre davantage sur l'innocuité de BAY 3771249 et son efficacité chez les personnes atteintes d'un cancer colorectal avancé ou métastatique présentant une mutation KRAS G12D
Protocole principal : Étude en ouvert visant à évaluer la sécurité, la tolérance, la pharmacocinétique, la pharmacodynamique et l'efficacité du BAY 3771249 en monothérapie ou en association avec d'autres traitements anticancéreux chez des participants présentant des tumeurs solides porteuses d'une mutation KRAS G12D Sous-protocole : Étude en ouvert, multicohorte visant à évaluer la sécurité, la tolérance, la pharmacocinétique, la pharmacodynamique et l'activité antitumorale préliminaire du BAY 3771249 en monothérapie et en association avec le cétuximab chez des participants présentant un adénocarcinome colorectal avancé/métastatique porteur d'une mutation KRAS G12D
Researchers are looking for a better way to treat people who have advanced or metastatic colorectal cancer (CRC) with a specific mutation, the G12D mutation, in a protein called KRAS.
Colorectal cancer (CRC) is a common type of cancer that affects the large bowel (colon) or the rectum (the section at the end of the bowel). When CRC spreads to other parts of the body, it is called advanced or metastatic CRC. Some people with CRC have the G12D mutation in the KRAS protein. This mutation is linked to a poorer outlook and fewer treatment options. Currently, there are no approved treatments that specifically target this mutation.
KRAS is a protein that helps control how cells grow and divide. When it is mutated, it can cause cells to grow uncontrollably, leading to cancer. The study drug, BAY 3771249, is designed to block the activity of KRAS with G12D mutation, which may help slow or stop the growth of cancer cells. BAY 3771249 can be given alone or together with another drug called cetuximab.
The main purpose of this study is to learn how safe BAY 3771249 is, how well people tolerate it, how the body processes the drug, and whether it can help shrink or control tumors in people with advanced or metastatic CRC that has the KRAS G12D mutation. The study will also look at how BAY 3771249 works when given alone or with cetuximab, especially in people who have already tried other treatments for their cancer.
Researchers will measure, among others:
The number and seriousness of health problems (adverse events) after receiving BAY 3771249.
The number of participants who experience a dose-limiting side effect (DLT) at each dose level.
The number of participants whose tumors shrink or disappear (overall response rate, ORR) as measured by standard criteria.
How much of the drug is in the blood over time (AUC) and the highest amount in the blood (Cmax).
Some participants will receive BAY 3771249 alone (monotherapy), and others will receive BAY 3771249 with cetuximab (combination therapy).
The study will start with lower doses and gradually increase to find the highest safe dose (dosage escalation). After the safe dose is found, more participants may join the study to receive it (dosage expansion). In some parts of the study, participants may be randomly assigned to different groups or doses. The study is open-label, meaning both participants and doctors know which treatment is being given.
An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, even if they do not think it is related to the study treatment.
The study doctors and their team will contact participants to learn about their health until they complete the study.
If a participant benefits from the treatment, it might be possible to continue receiving BAY 3771249 after the end of the study. The findings from this study may help develop a new treatment option for people with advanced or metastatic CRC with a KRAS G12D mutation.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Estimé)
Phase
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Bayer Clinical Trials Contact
- Numéro de téléphone: 18888422937
- E-mail: clinical-trials-contact@bayer.com
Lieux d'étude
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New South Wales
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Albury, New South Wales, Australie, 2640
- Pas encore de recrutement
- Border Medical oncology - Albury Wodonga Regional Cancer Centre
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Waratah, New South Wales, Australie, 2298
- Recrutement
- Calvary Mater Hospital Newcastle - Oncology
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Victoria
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Malvern, Victoria, Australie, 3144
- Pas encore de recrutement
- Cabrini Health Oncology Research
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East Flanders
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Ghent, East Flanders, Belgique, 9000
- Pas encore de recrutement
- Ghent University Hospital | Drug Research Unit Department
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Capital Region / Region Hovedstaden
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Copenhagen, Capital Region / Region Hovedstaden, Danemark, 2100
- Pas encore de recrutement
- Rigshospitalet Copenhagen University Hospital | Oncology Department
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Region of Southern Denmark / Region Syddanmark
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Odense, Region of Southern Denmark / Region Syddanmark, Danemark, 5000
- Pas encore de recrutement
- Odense University Hospital | Svendborg Sygehus - Oncology Department
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Barcelona
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Barcelona, Barcelona, Espagne, 08035
- Pas encore de recrutement
- Hospital Universitari Vall D Hebron | Oncologia
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Madrid
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Madrid, Madrid, Espagne, 28050
- Pas encore de recrutement
- Hospital Universitario Hm Sanchinarro | Oncologia
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Uusimaa
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Helsinki, Uusimaa, Finlande, 00029
- Pas encore de recrutement
- HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Syöpäkeskus
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Roma, Italie, 00128
- Pas encore de recrutement
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase I
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North Holland
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Amsterdam, North Holland, Pays-Bas, 1066 CX
- Pas encore de recrutement
- Nederlands Kanker Instituut
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Singapore, Singapour, 119074
- Recrutement
- National University Hospital Medical Centre
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Singapore, Singapour, 168583
- Recrutement
- National Cancer Center Singapore - Oncology Department
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Stockholm County
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Stockholm, Stockholm County, Suède, 171 76
- Pas encore de recrutement
- Karolinska Universitetssjukhuset - Solna - Fas I-enheten Solna CKC
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Arizona
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Phoenix, Arizona, États-Unis, 85054
- Pas encore de recrutement
- Mayo Clinic - Cancer Center - Phoenix
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California
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Duarte, California, États-Unis, 91010
- Recrutement
- City of Hope - Duarte Cancer Center
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San Diego, California, États-Unis, 92037
- Pas encore de recrutement
- UC San Diego Health - Moores Cancer Center
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Colorado
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Denver, Colorado, États-Unis, 80218
- Retiré
- Sarah Cannon Research Institute at HCA HealthONE Presbyterian St. Luke's
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New York
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New York, New York, États-Unis, 10029
- Pas encore de recrutement
- Icahn School of Medicine at Mount Sinai - Oncology
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Texas
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Irving, Texas, États-Unis, 75039
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- NEXT Dallas - Oncology Department
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San Antonio, Texas, États-Unis, 78229
- Recrutement
- START | San Antonio
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- KRAS G12D mutated solid tumor
- Participant must be ≥18 years old or the legal age of consent in the jurisdiction in which the study is taking place when signing the screening ICF
- At least one measurable lesion as per RECIST v1.1. outside the CNS
- Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1
- Male or Female: Contraceptive use by participant or participant's partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Life expectancy of at least 3 months in the opinion of the Investigator
- Histologically/pathologically documented diagnosis of advanced/metastatic adenocarcinoma of the colon and rectum.
- Adequate hematologic and end-organ function
Exclusion Criteria:
- Leptomeningeal disease or carcinomatous meningiti
- Uncontrolled and/or active/symptomatic brain metastases.
- Significant traumatic injury or major surgical procedure within 4 weeks of first dose of study intervention
- Known hypersensitivity to any component of study intervention
- Previous (within 3 years) or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in the respective substudy.
- Active infection requiring systemic anti-infective therapy within 14 days of first dose of study intervention
- Known HIV infection
- Active Hepatitis B virus (HBV) infection
- Active Hepatitis C virus (HCV) infection
- Significant cardiac disorder
- History of risk factors for torsade de pointes (TdP) (e.g., heart failure, family history of long QT syndrome)
- Participants with inadequately managed diabetes as assessed by the Investigator
- Toxicities from prior anticancer therapy, defined as not having resolved to Grade ≤1 or as specified in the respective substudy protocol as per NCI CTCAE v.6.0 with the following exceptions: Alopecia of any grade, Peripheral neuropathy Grade ≤2, Autoimmune endocrine disorders Grade ≤2 managed with stable endocrine replacement therapy
- History of (non-infectious) pneumonitis/interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis (unless it has resolved without sequelae without use of steroids), or any evidence of clinically-active pneumonitis/ILD
- History of the following eye disorders: keratitis, ulcerative keratitis
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation séquentielle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Dosage escalation
In the dosage escalation part, different dose levels of BAY 3771249 administered as monotherapy and in combination with cetuximab are planned. |
Oral Intravenous (IV) infusion |
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Expérimental: Dosage expansion
In the dosage expansion part, participants will receive BAY 3771249 either as monotherapy or in combination with cetuximab until disease progression as defined by RECIST v1.1, the occurrence of unacceptable toxicity, or the fulfillment of any other withdrawal criteria. |
Oral Intravenous (IV) infusion |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Change from baseline in laboratory test results
Délai: Up to approximately 2 years
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Hematology, serum chemistry, urinalysis and coagulation tests. Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Blood pressure
Délai: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Body temperature
Délai: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Oxygen saturation
Délai: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Pulse rate
Délai: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Respiratory rate
Délai: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Number of participants experiencing a dose-limiting toxicity (DLT) at each dosage
Délai: Up to approximately 3 weeks
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Applicable in Dose escalation part |
Up to approximately 3 weeks
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Number of participants with Treatment-emergent adverse events (TEAEs)
Délai: Up to approximately 2 years.
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years.
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Objective response rate (ORR) as determined by the Investigator according to RECIST v1.1
Délai: Up to approximately 2 years
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Severity of TEAEs
Délai: Up to approximately 2 years.
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Applicable in Dosage escalation and expansion |
Up to approximately 2 years.
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Pharmacokinetics (PK) parameters such as area under the concentration vs time curve (AUC)
Délai: Up to approximately 2 years
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Applicable in Dosage escalation |
Up to approximately 2 years
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PK parameters such as maximum observed drug concentration (Cmax)
Délai: Up to approximately 2 years
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Applicable in Dosage escalation |
Up to approximately 2 years
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Collaborateurs et enquêteurs
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 23111-1
- 2025 (Subvention/contrat des NIH des États-Unis)
- 2025-523648-11-00 (Ctis)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Currently, there is no established plan for the sharing of Individual Patient Data (IPD) from this study. The availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA 'Principles for responsible clinical trial data sharing.' This pertains to the scope, timepoint, and process of data access. As such, Bayer commits to considering requests from qualified researchers for patient- / study-level clinical trial data, and documents from clinical trials involving medicines and indications approved in the US and EU. However, this commitment does not reflect an active IPD sharing plan. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Researchers can use www.vivli.org to request access to IPD and documents from clinical studies to conduct research. Information on Bayer's criteria for listing studies is provided in the member section of the portal.
Informations sur les médicaments et les dispositifs, documents d'étude
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