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

Condition(s) studied

Investigational drug(s) / intervention(s)

BAY 3771249: Oral

Cetuximab: Intravenous (IV) infusion

Study 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.

Eligibility

Primary outcome measure(s)

• Number of participants with Treatment-emergent adverse events (TEAEs) — Up to approximately 2 years.
  Applicable in Dosage escalation and expansion
• Severity of TEAEs — Up to approximately 2 years.
  Applicable in Dosage escalation and expansion
• Change from baseline in vital signs: Pulse rate — Up to approximately 2 years
  Applicable in Dosage escalation and expansion
• Change from baseline in vital signs: Oxygen saturation — Up to approximately 2 years
  Applicable in Dosage escalation and expansion
• Change from baseline in vital signs: Respiratory rate — Up to approximately 2 years
  Applicable in Dosage escalation and expansion
• Change from baseline in vital signs: Blood pressure — Up to approximately 2 years
  Applicable in Dosage escalation and expansion
• Change from baseline in vital signs: Body temperature — Up to approximately 2 years
  Applicable in Dosage escalation and expansion
• Change from baseline in laboratory test results — Up to approximately 2 years
  Hematology, serum chemistry, urinalysis and coagulation tests. Applicable in Dosage escalation and expansion
• Number of participants experiencing a dose-limiting toxicity (DLT) at each dosage — Up to approximately 3 weeks
  Applicable in Dose escalation part
• Objective response rate (ORR) as determined by the Investigator according to RECIST v1.1 — Up to approximately 2 years
  Applicable in Dosage escalation and expansion

Trial sites (21)

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