Researchers are looking for a better way to treat people who have advanced solid cancers with a KRASG12C mutation.
Sotorasib is a drug that targets cancer cells which contain mutated KRASG12C protein; it can stop the cancer cells from growing and can lead to their death. Sotorasib is already approved to be used by doctors. However, when sotorasib works, it normally only works for a period of time, after which the cancer starts to grow again, and the patient may need a different treatment.
BAY3498264 is a drug that is currently under development. It is expected to prevent the activity of a protein called son of sevenless 1 (SOS1). The SOS1 protein works together with KRAS; by blocking the activity of SOS1 with BAY3498264, it is hoped that the benefit offered by treatment with sotorasib may be increased - for example, resulting in a longer or deeper response.
The main purpose of this first-in-human study is to learn how safe BAY3498264 is when given together with sotorasib and what is the maximum dose of BAY3498264 that can be safely given to participants together with sotorasib.
During the study, participants will receive the following treatments:
* BAY3498264: participants will first receive BAY3498264 alone for seven days and then BAY3498264 in combination with sotorasib. These combination treatments will be given in cycles, each lasting 21 days. * Sotorasib: participants will receive a standard, approved dose of Sotorasib once every day with BAY3498264.
The treatment will continue for as long as participants benefit from it without any severe medical problems or until they or their doctor decide to stop the treatment, or until their cancer starts to grow again despite the treatment (also called 'progression').
This study has 3 parts, the dose escalation part, the backfill part and the expansion part.
During the study, researchers will collect blood, urine, and take imaging scans like CT, PET, MRI, and X-rays, and examine the participants' heart health using an electrocardiogram (ECG). Participants' health is monitored throughout the study.
Histologically confirmed solid tumor malignancy with documented KRAS^G12C mutation as assessed by an appropriately accredited laboratory.
Documented disease progression after treatment with at least 1 prior standard of care (SoC) systemic therapy other than a G12C inhibitor for locally advanced or metastatic disease, and with no further standard treatment options available, or when standard treatment options are not acceptable and this study is a reasonable option.
Participants whose access to SoC therapies is limited due to regional access, refusal, intolerance, or eligibility may participate.
Prior G12C inhibitor treatment is permitted. Participants receiving prior G12C inhibitor therapy must have documented disease progression after treatment, or have discontinued that treatment due to intolerance.
'Active' is defined as untreated brain lesions (new or progressing) or symptomatic brain lesions (as determined by the investigator).
Grade ≥2 ILD,
Drug-induced ILD,
Radiation pneumonitis that required steroid treatment within the last 12 months.
Sequential
BAY3498264
DrugOral
Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) categorized by severity.
Maximum tolerated dose (MTD) or Maximum administered dose (MAD) of BAY 3498264 in combination with sotorasib.
Number of participants with Dose-limiting toxicity (DLTs) during the DLT observation period categorized by severity.
Maximum observed drug concentration in plasma (Cmax) of the respective dosing interval of BAY3498264 after single dose and multiple dose administrations.
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by investigator assessment.
Recommended dose(s) and schedule(s) of BAY 3498264 to be used in combination with sotorasib for further development stages.
