A Phase I Study of BAY3498264 Given Together With Sotorasib in Participants Who Have Advanced Solid Cancers With Specific Genetic Changes Called KRASG12C Mutation

Trial Title: A Phase I Study of BAY3498264 Given Together With Sotorasib in Participants Who Have Advanced Solid Cancers With Specific Genetic Changes Called KRASG12C Mutation

NCT ID: NCT06659341

Condition: Advanced Solid Tumors Harboring KRAS G12C Mutation

Study type: Interventional

Study phase: Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: BAY3498264
Description: Oral
Arm group label: Backfill cohorts
Arm group label: Dose escalation
Arm group label: Exploratory expansion cohorts

Summary: 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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Histologically confirmed solid tumor malignancy with documented KRASG12C 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. - Adequate archival formalin-fixed paraffin-embedded tumor tissue available (preferably no older than 6 months, obtained after the last targeted therapy). If archival material is not available, a fresh tumor biopsy should ideally be obtained if safe and feasible. - Eastern Cooperative Oncology Group (ECOG) of 0 to 2 and life expectancy of at least 12 weeks. Exclusion Criteria: - Active central nervous system (CNS) tumors including metastatic brain disease, at the time of screening. 1. 'Active' is defined as untreated brain lesions (new or progressing) or symptomatic brain lesions (as determined by the investigator) 2. Participants who have received treatment (e.g. surgery or radiotherapy) for brain metastases ending at least 4 weeks before cycle 1 day 1 (C1D1) may be eligible if, at the point of study entry: i. their condition is considered stable by the investigator ii. they have no residual neurological symptoms (Grade >2) iii. a follow-up Magnetic resonance imaging (MRI) scan during the screening period shows no progression or new lesions iv. they do not need systemic corticosteroids to treat symptoms of brain metastasis - Any grade active pneumonitis or interstitial lung disease (ILD), or past medical history of: 1. Grade ≥2 ILD, 2. Drug-induced ILD 3. Radiation pneumonitis that required steroid treatment within the last 12 months - Additional malignancy within the past 3 years, except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder tumors, localized prostate cancer or other tumors that in the opinion of the investigator, in agreement with the Sponsor, are considered cured or not immediately life-threatening, and will not interfere with the scientific goals of this study. - Any positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating the presence of virus. - Active HBV (chronic or acute; defined as having a known positive HBsAg test at the time of screening) except for participants on antiviral therapy for HBV with an undetectable or low viral load. - Participants with past HBV infection or resolved HBV infection (defined as the presence of HBcAb and absence of HBsAg) are eligible if HBV DNA is negative. - Participants positive for HCV antibody unless polymerase chain reaction is negative for HCV RNA. Any prior antiviral therapy must be completed at least 28 days before the first dose of study intervention.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Macquarie University Hospital

Address:
City: Macquarie Park
Zip: 2109
Country: Australia

Facility:
Name: Peninsula and Southeast Oncology

Address:
City: Frankston
Zip: 3199
Country: Australia

Facility:
Name: Rigshospitalet - Kræftbehandling

Address:
City: Copenhagen OE
Zip: 2100
Country: Denmark

Facility:
Name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica

Address:
City: Roma
Zip: 00168
Country: Italy

Facility:
Name: Gruppo Humanitas - Humanitas Research Hospital - Cancer Center

Address:
City: Rozzano
Zip: 20089
Country: Italy

Facility:
Name: Institut Català d'Oncologia Hospitalet

Address:
City: L Hospitalet De Llobregat
Zip: 8907
Country: Spain

Facility:
Name: Hospital Universitari Vall d'Hebron - Vall d'Hebron Institut d'Oncologia (VHIO)

Address:
City: Barcelona
Zip: 8035
Country: Spain

Facility:
Name: The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) - Sutton

Address:
City: Sutton
Zip: SM2 5PT
Country: United Kingdom

Facility:
Name: The Christie NHS Foundation Trust - Christie Hospital

Address:
City: Manchester
Zip: M20 4BX
Country: United Kingdom

Start date: November 7, 2024

Completion date: November 5, 2027

Lead sponsor:
Agency: Bayer
Agency class: Industry

Source: Bayer

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06659341