Studie zaměřená na získání dalších informací o bezpečnosti přípravku BAY 3771249 a jeho účinnosti u pacientů s pokročilým nebo metastatickým kolorektálním karcinomem s mutací KRAS G12D
Hlavní protokol: Otevřená studie pro vyhodnocení bezpečnosti, snášenlivosti, farmakokinetiky, farmakodynamiky a účinnosti přípravku BAY 3771249 jako monoterapie nebo v kombinaci s dalšími léčbami nádorů u účastníků s pevnými nádory s mutací KRAS G12D Podstudijní protokol: Otevřená, vícekohortní studie pro vyhodnocení bezpečnosti, snášenlivosti, farmakokinetiky, farmakodynamiky a předběžné protinádorové aktivity přípravku BAY 3771249 jako monoterapie a v kombinaci s cetuximabem u účastníků s pokročilým/metastatickým kolorektálním adenokarcinomem s mutací 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.
Přehled studie
Postavení
Intervence / Léčba
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: Bayer Clinical Trials Contact
- Telefonní číslo: 18888422937
- E-mail: clinical-trials-contact@bayer.com
Studijní místa
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New South Wales
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Albury, New South Wales, Austrálie, 2640
- Zatím nenabíráme
- Border Medical oncology - Albury Wodonga Regional Cancer Centre
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Waratah, New South Wales, Austrálie, 2298
- Nábor
- Calvary Mater Hospital Newcastle - Oncology
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Victoria
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Malvern, Victoria, Austrálie, 3144
- Zatím nenabíráme
- Cabrini Health Oncology Research
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East Flanders
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Ghent, East Flanders, Belgie, 9000
- Zatím nenabíráme
- Ghent University Hospital | Drug Research Unit Department
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Capital Region / Region Hovedstaden
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Copenhagen, Capital Region / Region Hovedstaden, Dánsko, 2100
- Zatím nenabíráme
- 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, Dánsko, 5000
- Zatím nenabíráme
- Odense University Hospital | Svendborg Sygehus - Oncology Department
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Uusimaa
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Helsinki, Uusimaa, Finsko, 00029
- Zatím nenabíráme
- HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Syöpäkeskus
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North Holland
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Amsterdam, North Holland, Holandsko, 1066 CX
- Zatím nenabíráme
- Nederlands Kanker Instituut
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Roma, Itálie, 00128
- Zatím nenabíráme
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase I
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Singapore, Singapur, 119074
- Nábor
- National University Hospital Medical Centre
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Singapore, Singapur, 168583
- Nábor
- National Cancer Center Singapore - Oncology Department
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Arizona
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Phoenix, Arizona, Spojené státy, 85054
- Zatím nenabíráme
- Mayo Clinic - Cancer Center - Phoenix
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California
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Duarte, California, Spojené státy, 91010
- Nábor
- City of Hope - Duarte Cancer Center
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San Diego, California, Spojené státy, 92037
- Zatím nenabíráme
- UC San Diego Health - Moores Cancer Center
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Colorado
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Denver, Colorado, Spojené státy, 80218
- Staženo
- 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, Spojené státy, 10029
- Zatím nenabíráme
- Icahn School of Medicine at Mount Sinai - Oncology
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Texas
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Irving, Texas, Spojené státy, 75039
- Nábor
- NEXT Dallas - Oncology Department
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San Antonio, Texas, Spojené státy, 78229
- Nábor
- START | San Antonio
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Barcelona
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Barcelona, Barcelona, Španělsko, 08035
- Zatím nenabíráme
- Hospital Universitari Vall D Hebron | Oncologia
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Madrid
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Madrid, Madrid, Španělsko, 28050
- Zatím nenabíráme
- Hospital Universitario Hm Sanchinarro | Oncologia
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Stockholm County
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Stockholm, Stockholm County, Švédsko, 171 76
- Zatím nenabíráme
- Karolinska Universitetssjukhuset - Solna - Fas I-enheten Solna CKC
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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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Experimentální: 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 |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change from baseline in laboratory test results
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: Up to approximately 2 years
|
Applicable in Dosage escalation and expansion |
Up to approximately 2 years
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Change from baseline in vital signs: Respiratory rate
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: Up to approximately 2 years.
|
Applicable in Dosage escalation and expansion |
Up to approximately 2 years.
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Pharmacokinetics (PK) parameters such as area under the concentration vs time curve (AUC)
Časové okno: 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)
Časové okno: Up to approximately 2 years
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Applicable in Dosage escalation |
Up to approximately 2 years
|
Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 23111-1
- 2025 (Grant/smlouva NIH USA)
- 2025-523648-11-00 (Ctis)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu 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.
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