Combining BAY3498264 with Sotorasib for Advanced Solid Cancers with KRAS G12C Mutation

Phase 1 Study of a SOS1 Inhibitor, BAY 3498264, in Combination in Participants With Advanced KRASG12C-mutated Solid Tumors

This study is testing a new drug called BAY3498264 combined with Sotorasib to see if it can help people with advanced solid cancers that have a specific KRAS G12C mutation.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 104 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Bayer (Industry-sponsored)
• Drugs / interventions: Radiation
• Locations: 10 sites (Albury, New South Wales and 9 other locations)
• Trial ID: NCT06659341 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of BAY3498264 when administered alongside Sotorasib in patients with advanced solid tumors harboring the KRAS G12C mutation. Sotorasib is an approved treatment that targets cancer cells with this specific mutation, but its effectiveness can diminish over time. BAY3498264, currently in development, aims to enhance the effects of Sotorasib by inhibiting the SOS1 protein, potentially leading to improved treatment outcomes. The study will assess how well these two drugs work together in this patient population.

Who should consider this trial

Good fit: Ideal candidates include individuals with advanced solid tumors confirmed to have the KRAS G12C mutation who have experienced disease progression after prior treatments.

Not a fit: Patients without the KRAS G12C mutation or those who have not progressed after standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a more effective treatment option for patients with advanced solid tumors that have the KRAS G12C mutation.

How similar studies have performed: While this approach is novel, similar studies targeting KRAS mutations have shown promise, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* 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.
* 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 the start of study intervention 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.

Where this trial is running

Albury, New South Wales and 9 other locations

• Border Medical oncology - Albury Wodonga Regional Cancer Centre — Albury, New South Wales, Australia (Recruiting)
• Macquarie University Hospital - Oncology Department — Macquarie Park, New South Wales, Australia (Recruiting)
• Peninsula and Southeast Oncology — Frankston, Victoria, Australia (Recruiting)
• Rigshospitalet - Kræftbehandling — Copenhagen, Capital Region, Denmark (Recruiting)
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica — Rome, Lazio, Italy (Recruiting)
• Gruppo Humanitas - Humanitas Research Hospital - Cancer Center — Rozzano, Italy (Recruiting)
• Institut Catala D'oncologia | Hospitalet | Oncologia — L'Hospitalet de Llobregat, Barcelona, Spain (Recruiting)
• Hospital Universitari Vall D Hebron | Oncologia — Barcelona, Spain (Not_yet_recruiting)
• The Christie NHS Foundation Trust - Christie Hospital — Manchester, Greater Manchester, United Kingdom (Recruiting)
• The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) - Sutton — Sutton, Surrey, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Bayer Clinical Trials Contact

Conditions Advanced Solid Tumors Harboring KRAS G12C Mutation