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RecruitingPhase 1

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

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests how safe BAY 3771249 is and whether it can shrink or control cancer, alone or with cetuximab. It is for adults with advanced colon or rectal cancer that has a change called KRAS G12D. Researchers will also study how the body handles the drug.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be at least 18 years old or the legal age to consent where the study takes place.
  • Have a solid tumor with the KRAS G12D change.
  • Have advanced or spreading adenocarcinoma, a type of colon or rectal cancer, confirmed by a tissue test.
  • Have at least one tumor that can be measured outside the brain and spinal cord.
  • Be fully active or able to do light work despite some limits on hard physical activity.
  • Follow local study rules for birth control, including rules for partners.
  • Be expected by the study doctor to live at least 3 months.
  • Have blood test results and organ function that meet study requirements.

Who can't join

  • Cancer in the tissues around the brain or spinal cord, or cancer spread to the brain that is uncontrolled, active, or causing symptoms.
  • A serious injury or major surgery within 4 weeks before treatment, or a known allergy to any part of the study treatment.
  • A different cancer now or within the past 3 years.
  • An active infection needing medicine that treats the whole body within 14 days before treatment; known HIV; or active hepatitis B or C.
  • A serious heart problem, risk factors for a dangerous heart rhythm called torsade de pointes, or diabetes that is not well controlled.
  • Side effects from past cancer treatment that have not improved to mild levels or met study rules. Exceptions include hair loss, some nerve damage, and some immune-related hormone problems controlled with stable hormone treatment.
  • Current lung inflammation or a history of certain lung inflammation or scarring. Past radiation-related lung inflammation may be allowed if it cleared without steroids or lasting problems.
  • A history of inflammation or sores in the clear front layer of the eye.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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 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

Study sites (7)

AZ

CA

CO

  • Sarah Cannon Research Institute at HCA HealthONE Presbyterian St. Luke's · Denver, CO 80218More trials in Denver

NY

TX