A Study to Learn More About How Safe BAY 3771249 is and How Well it Works in People With Advanced or Metastatic Colorectal Cancer That Has a KRAS G12D Mutation

NCT07535112
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
130
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Lead sponsor
Bayer
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Start date
2026-04-07
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Number of sites
21
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Summary
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.
clinicaltrials.gov
Short title
A Study to Learn More About How Safe BAY 3771249 is and How Well it Works in People With Advanced or Metastatic Colorectal Cancer That Has a KRAS G12D Mutation
clinicaltrials.gov
Official title
Master Protocol: An Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of BAY 3771249 as Monotherapy or Combination With Other Cancer Treatments in Participants With Solid Tumors Harboring a KRAS G12D Mutation. Substudy Protocol: An Open-label, Multi-cohort Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-tumor Activity of BAY 3771249 as Monotherapy and in Combination With Cetuximab in Participants With Advanced/Metastatic Colorectal Adenocarcinoma Harboring a KRAS G12D Mutation
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2030-07-09
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First posted
2026-04-16
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Registry last updated
2026-10-05
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Primary completion date
2029-07-27
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Start date
2026-04-07
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Participants
130
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Participant count basis
Estimated
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Planned participants
130
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Protocol amendments
3
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Number of sites
21
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Bayer
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07535112
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ClinicalTrials.gov ID
NCT07535112
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Registry record
Open registry record
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Allocation
Not applicable
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Change from baseline in laboratory test results

    Timeframe: Up to approximately 2 years

    Hematology, serum chemistry, urinalysis and coagulation tests. Applicable in Dosage escalation and expansion

  2. Change from baseline in vital signs: Blood pressure

    Timeframe: Up to approximately 2 years

    Applicable in Dosage escalation and expansion

  3. Change from baseline in vital signs: Body temperature

    Timeframe: Up to approximately 2 years

    Applicable in Dosage escalation and expansion

  4. Change from baseline in vital signs: Oxygen saturation

    Timeframe: Up to approximately 2 years

    Applicable in Dosage escalation and expansion

  5. Change from baseline in vital signs: Pulse rate

    Timeframe: Up to approximately 2 years

    Applicable in Dosage escalation and expansion

  6. Change from baseline in vital signs: Respiratory rate

    Timeframe: Up to approximately 2 years

    Applicable in Dosage escalation and expansion

  7. Number of participants experiencing a dose-limiting toxicity (DLT) at each dosage

    Timeframe: Up to approximately 3 weeks

    Applicable in Dose escalation part

  8. Number of participants with Treatment-emergent adverse events (TEAEs)

    Timeframe: Up to approximately 2 years.

    Applicable in Dosage escalation and expansion

  9. Objective response rate (ORR) as determined by the Investigator according to RECIST v1.1

    Timeframe: Up to approximately 2 years

    Applicable in Dosage escalation and expansion

  10. Severity of TEAEs

    Timeframe: Up to approximately 2 years.

    Applicable in Dosage escalation and expansion

  1. Pharmacokinetics (PK) parameters such as area under the concentration vs time curve (AUC)

    Timeframe: Up to approximately 2 years

    Applicable in Dosage escalation

  2. PK parameters such as maximum observed drug concentration (Cmax)

    Timeframe: Up to approximately 2 years

    Applicable in Dosage escalation

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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
Sources for eligibility
clinicaltrials.gov

  • Mayo Clinic - Cancer Center - PhoenixPhoenix, United StatesNot yet recruiting
  • City of Hope - Duarte Cancer CenterDuarte, United StatesRecruiting
  • UC San Diego Health - Moores Cancer CenterSan Diego, United StatesNot yet recruiting
  • Sarah Cannon Research Institute at HCA HealthONE Presbyterian St. Luke'sDenver, United StatesWithdrawn
  • Icahn School of Medicine at Mount Sinai - OncologyNew York, United StatesNot yet recruiting
  • NEXT Dallas - Oncology DepartmentIrving, United StatesRecruiting
  • START | San AntonioSan Antonio, United StatesRecruiting
  • Border Medical oncology - Albury Wodonga Regional Cancer CentreAlbury, AustraliaNot yet recruiting
  • Calvary Mater Hospital Newcastle - OncologyWaratah, AustraliaRecruiting
  • Cabrini Health Oncology ResearchMalvern, AustraliaNot yet recruiting
  • Ghent University Hospital | Drug Research Unit DepartmentGhent, BelgiumNot yet recruiting
  • Rigshospitalet Copenhagen University Hospital | Oncology DepartmentCopenhagen, DenmarkNot yet recruiting
  • Odense University Hospital | Svendborg Sygehus - Oncology DepartmentOdense, DenmarkNot yet recruiting
  • HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - SyöpäkeskusHelsinki, FinlandNot yet recruiting
  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase IRoma, ItalyNot yet recruiting
  • Nederlands Kanker InstituutAmsterdam, NetherlandsNot yet recruiting
  • National University Hospital Medical CentreSingapore, SingaporeRecruiting
  • National Cancer Center Singapore - Oncology DepartmentSingapore, SingaporeRecruiting
  • Hospital Universitari Vall D Hebron | OncologiaBarcelona, SpainNot yet recruiting
  • Hospital Universitario Hm Sanchinarro | OncologiaMadrid, SpainNot yet recruiting
  • Karolinska Universitetssjukhuset - Solna - Fas I-enheten Solna CKCStockholm, SwedenNot yet recruiting
Sources for sites
clinicaltrials.gov

  • 2025
  • 2025-523648-11-00
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Targets (1)