Advanced Solid Tumors Harboring KRAS G12C MutationPhase 1NCT06659341
A Phase I Study of BAY3498264 Given Together With Sotorasib in Participants Who Have Advanced Solid Cancers With Specific Genetic Changes Called KRASG12C Mutation
A Phase 1 study testing BAY3498264 in people with Advanced Solid Tumors Harboring KRAS G12C Mutation, run by Bayer at 11 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors Harboring KRAS G12C Mutation
- What is being tested?
- BAY3498264
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 11 sitesin 5 countries
- Study dates
- 8 Nov 2024to 6 Sep 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Active central nervous system (CNS) tumors including metastatic brain disease, at the time of screening.
- 'Active' is defined as untreated brain lesions (new or progressing) or symptomatic brain lesions (as determined by the investigator).
- 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:
- 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.
- 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:
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- Grade ≥2 ILD,
- Drug-induced ILD,
- 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.
Trial locations and contacts
11 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
11 sites in 5 countries
Australia4 sites, 3 recruiting
- Recruiting
Border Medical oncology - Albury Wodonga Regional Cancer Centre
Albury, New South Wales, 2640
- Recruiting
Peninsula and Southeast Oncology
Frankston, Victoria, 3199
- Recruiting
Macquarie University Hospital - Oncology Department
Macquarie Park, New South Wales, 2109
- Withdrawn
Cabrini Health Oncology Research
Malvern, Victoria, 3144
Italy2 sites, 2 recruiting
- Recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
Rome, Lazio, 00168
- Recruiting
Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia
Rozzano, Lombardy, 20089
Spain2 sites, 2 recruiting
- Recruiting
Hospital Universitari Vall D Hebron | Oncologia
Barcelona, 08035
- Recruiting
Institut Catala D'oncologia | Hospitalet | Oncologia
Barcelona, 8907
United Kingdom2 sites, 2 recruiting
- Recruiting
The Christie Hospital | Oncology
Manchester, Greater Manchester, M20 4BX
- Recruiting
The Royal Marsden (Surrey) | Oak Foundation Drug Development Unit
Sutton, Surrey, SM2 5PT
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet Copenhagen University Hospital | Oncology Department
Copenhagen, Capital Region / Region Hovedstaden, 2100
About this study
Official title: Phase 1 Study of a SOS1 Inhibitor, BAY 3498264, in Combination in Participants With Advanced KRASG12C-mutated Solid Tumors
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.
Read more
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.
- Being tested
- BAY3498264
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY3498264Drug
Oral
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | During dose escalation, at each dose level BAY3498264 monotherapy will be administered for 7 days as a safety run-in, prior to introduction of a combination agent (sotorasib) for 21-day treatment cycles. Intra-participant dose escalation will be implemented: participants will be able to move to a cohort offering a higher dose level of BAY3498264 provided protocol-specified criteria are met. Receives: Drug: BAY3498264 |
| Backfill cohorts | Experimental | Backfill cohorts may be initiated concurrently with dose escalation cohorts to generate additional safety, PK, and PD data to facilitate the selection of the optimal doses for use in further development. Receives: Drug: BAY3498264 |
| Exploratory expansion cohorts | Experimental | Exploratory expansion cohorts may be recruited to provide additional safety, PK/PD, and efficacy data. Receives: Drug: BAY3498264 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) categorized by severity.
Measured: 30-35 days after the last dose
Maximum tolerated dose (MTD) or Maximum administered dose (MAD) of BAY 3498264 in combination with sotorasib.
Measured: Approximate 3 years
Number of participants with Dose-limiting toxicity (DLTs) during the DLT observation period categorized by severity.
Measured: DLT evaluation period (Cycle 1) includes 28 days
Maximum observed drug concentration in plasma (Cmax) of the respective dosing interval of BAY3498264 after single dose and multiple dose administrations.
Measured: Multiple time points: Cycle 1 28-day cycle followed by 21-day treatment cycles
Area under the concentration vs. time curve (AUC) of the respective dosing interval of BAY3498264 after single dose and multiple dose administrations.
Measured: Multiple time points: Cycle 1 28-day cycle followed by 21-day treatment cycles
Secondary outcomes (2)
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by investigator assessment.
Measured: Every 6 weeks (±7 days) for the first 36 weeks and every 9 weeks (± 7 days) thereafter until radiological disease progression (PD) occurs
Recommended dose(s) and schedule(s) of BAY 3498264 to be used in combination with sotorasib for further development stages.
Measured: Approximate 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2024
- Study start8 Nov 2024
- Primary completion26 Apr 2027 (estimated)
- Study completion6 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid Tumors Harboring KRAS G12C MutationStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06659341
- Sponsor's protocol ID
- 22676
- Other IDs
- 2024-513300-34-00
- Status last verified
- 19 Oct 2026
- First submitted
- 15 Oct 2024
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.