Advanced/Metastatic Colorectal AdenocarcinomaPhase 1NCT07535112
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
A Phase 1 study testing BAY 3771249 and Cetuximab in people with Advanced/Metastatic Colorectal Adenocarcinoma, run by Bayer at 21 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced/Metastatic Colorectal Adenocarcinoma
- What is being tested?
- BAY 3771249 and Cetuximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 21 sitesin 10 countries
- Study dates
- 7 Apr 2026to 9 Jul 2030
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
21 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 10 countries
United States7 sites, 6 recruiting
- Withdrawn
Sarah Cannon Research Institute at HCA HealthONE Presbyterian St. Luke's
Denver, Colorado, 80218
- Recruiting
City of Hope - Duarte Cancer Center
Duarte, California, 91010
- Recruiting
NEXT Dallas - Oncology Department
Irving, Texas, 75039
- Not yet recruiting
Icahn School of Medicine at Mount Sinai - Oncology
New York, New York, 10029
- Not yet recruiting
Mayo Clinic - Cancer Center - Phoenix
Phoenix, Arizona, 85054
- Recruiting
START | San Antonio
San Antonio, Texas, 78229
- Not yet recruiting
UC San Diego Health - Moores Cancer Center
San Diego, California, 92037
Australia3 sites, 3 recruiting
- Not yet recruiting
Border Medical oncology - Albury Wodonga Regional Cancer Centre
Albury, New South Wales, 2640
- Not yet recruiting
Cabrini Health Oncology Research
Malvern, Victoria, 3144
- Recruiting
Calvary Mater Hospital Newcastle - Oncology
Waratah, New South Wales, 2298
Denmark2 sites, 2 recruiting
- Not yet recruiting
Rigshospitalet Copenhagen University Hospital | Oncology Department
Copenhagen, Capital Region / Region Hovedstaden, 2100
- Not yet recruiting
Odense University Hospital | Svendborg Sygehus - Oncology Department
Odense, Region of Southern Denmark / Region Syddanmark, 5000
Singapore2 sites, 2 recruiting
- Recruiting
National University Hospital Medical Centre
Singapore, 119074
- Recruiting
National Cancer Center Singapore - Oncology Department
Singapore, 168583
Spain2 sites, 2 recruiting
- Not yet recruiting
Hospital Universitari Vall D Hebron | Oncologia
Barcelona, Barcelona, 08035
- Not yet recruiting
Hospital Universitario Hm Sanchinarro | Oncologia
Madrid, Madrid, 28050
Belgium1 site, 1 recruiting
- Not yet recruiting
Ghent University Hospital | Drug Research Unit Department
Ghent, East Flanders, 9000
Finland1 site, 1 recruiting
- Not yet recruiting
HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Syöpäkeskus
Helsinki, Uusimaa, 00029
Italy1 site, 1 recruiting
- Not yet recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase I
Roma, 00128
Netherlands1 site, 1 recruiting
- Not yet recruiting
Nederlands Kanker Instituut
Amsterdam, North Holland, 1066 CX
Sweden1 site, 1 recruiting
- Not yet recruiting
Karolinska Universitetssjukhuset - Solna - Fas I-enheten Solna CKC
Stockholm, Stockholm County, 171 76
About this study
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
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.
Read more
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.
- Being tested
- BAY 3771249, Cetuximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY 3771249Drug
Oral
CetuximabDrug
Intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| Dosage escalation | Experimental | In the dosage escalation part, different dose levels of BAY 3771249 administered as monotherapy and in combination with cetuximab are planned. Receives: Drug: BAY 3771249; Drug: Cetuximab |
| Dosage expansion | Experimental | 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. Receives: Drug: BAY 3771249; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in laboratory test results
Hematology, serum chemistry, urinalysis and coagulation tests. Applicable in Dosage escalation and expansion
Measured: Up to approximately 2 years
Change from baseline in vital signs: Blood pressure
Applicable in Dosage escalation and expansion
Measured: Up to approximately 2 years
Change from baseline in vital signs: Body temperature
Applicable in Dosage escalation and expansion
Measured: Up to approximately 2 years
Change from baseline in vital signs: Oxygen saturation
Applicable in Dosage escalation and expansion
Measured: Up to approximately 2 years
Change from baseline in vital signs: Pulse rate
Applicable in Dosage escalation and expansion
Measured: Up to approximately 2 years
Change from baseline in vital signs: Respiratory rate
Applicable in Dosage escalation and expansion
Measured: Up to approximately 2 years
Number of participants experiencing a dose-limiting toxicity (DLT) at each dosage
Applicable in Dose escalation part
Measured: Up to approximately 3 weeks
Number of participants with Treatment-emergent adverse events (TEAEs)
Applicable in Dosage escalation and expansion
Measured: Up to approximately 2 years.
Objective response rate (ORR) as determined by the Investigator according to RECIST v1.1
Applicable in Dosage escalation and expansion
Measured: Up to approximately 2 years
Severity of TEAEs
Applicable in Dosage escalation and expansion
Measured: Up to approximately 2 years.
Secondary outcomes (2)
Pharmacokinetics (PK) parameters such as area under the concentration vs time curve (AUC)
Applicable in Dosage escalation
Measured: Up to approximately 2 years
PK parameters such as maximum observed drug concentration (Cmax)
Applicable in Dosage escalation
Measured: Up to approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2026
- Study start7 Apr 2026
- Primary completion27 Jul 2029 (estimated)
- Study completion9 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced/Metastatic Colorectal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07535112
- Sponsor's protocol ID
- 23111-1
- Other IDs
- 2025-523648-11-00, 2025
- Status last verified
- 1 Oct 2026
- First submitted
- 1 Apr 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.