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BAY 3771249 for advanced colorectal cancer with KRAS G12D mutation

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

Phase 1 Interventional Bayer · NCT07535112

This trial will test whether BAY 3771249, alone or with cetuximab, helps people with advanced or metastatic colorectal cancer that has a KRAS G12D mutation.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment130 (estimated)
Ages18 Years and up
SexAll
SponsorBayer Industry-sponsored
Drugs / interventionsradiation, cetuximab
Locations21 sites (Phoenix, Arizona and 20 other locations)
Trial IDNCT07535112 on ClinicalTrials.gov

What this trial studies

This is a phase 1, interventional trial enrolling adults with advanced or metastatic colorectal adenocarcinoma harboring the KRAS G12D mutation. Participants must have measurable disease, ECOG performance status ≤1, and adequate organ function, and they will receive BAY 3771249 either as monotherapy or combined with cetuximab. The study focuses on safety, tolerability, dose finding, and early signals of anti-tumor activity. Sites include three US cancer centers and treatment involves on-site visits for dosing and monitoring.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed advanced or metastatic colorectal adenocarcinoma carrying a KRAS G12D mutation, at least one measurable lesion outside the CNS, ECOG ≤1, and adequate hematologic and organ function are ideal candidates.

Not a fit: Patients without the KRAS G12D mutation, those with uncontrolled or symptomatic brain metastases or leptomeningeal disease, recent major surgery or significant traumatic injury within the protocol window, or inadequate organ function are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this could provide a targeted treatment option that slows tumor growth for people with KRAS G12D–mutant metastatic colorectal cancer.

How similar studies have performed: While KRAS G12C inhibitors have shown clinical success, targeted therapies for KRAS G12D remain largely early-stage and this approach is relatively novel in the clinic.

Eligibility criteria

Show full inclusion / exclusion criteria 
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 meningitis
* 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

Where this trial is running

Phoenix, Arizona and 20 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced/Metastatic Colorectal Adenocarcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.