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Solid Tumors, KRAS Mutation; SOS1Phase 1NCT04111458

A Study to Test Different Doses of BI 1701963 Alone and Combined With Trametinib in Patients With Different Types of Advanced Cancer (Solid Tumours With KRAS Mutation)

A Phase 1 study testing BI 1701963 and Trametinib in people with Solid Tumors, KRAS Mutation; SOS1, run by Boehringer Ingelheim at 8 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a study in adults with advanced cancer (solid tumours) in whom previous chemotherapy was not successful. Only people who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes cancer grow faster. The study tests 2 medicines called BI 1701963 and trametinib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors, KRAS Mutation; SOS1
What is being tested?
BI 1701963 and Trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
8 sitesin 3 countries
Study dates
4 Nov 2019to 30 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • All parts
  • Previously-identified activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation in tumour tissue or blood prior to screening
  • At least one target lesion that can be measured per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate organ function
  • Age ≥18 years of age, or over the legal age of consent as required by local legislation.
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  • Signed and dated written informed consent in accordance with GCP and local legislation prior to admission to the trial.
  • Women of childbearing potential who are not surgically sterilized must have a negative serum pregnancy test completed during the Screening period
  • Further inclusion criteria apply
  • Monotherapy and combination therapy dose escalation and monotherapy dose confirmation part
  • Documented disease progression despite appropriate prior standard therapies or for whom no standard therapy exists for their tumour type and disease stage
  • Combination dose confirmation and expansion cohort
  • Pathologically confirmed diagnosis of adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
  • Locally advanced stage IIIb or metastatic stage IV Non-small cell lung cancer (NSCLC)
  • Patients must have received both chemotherapy and immunotherapy

Who cannot join

  • All parts
  • Previous anticancer chemotherapy within 3 weeks of the first administration of trial drug.
  • Previous treatment with RAS, Mitogen-activated protein kinase (MAPK) or Son of sevenless 1 (SOS1) targeting agents
  • Major surgery performed within 4 weeks prior to start of treatment
  • Uncontrolled hypertension, congestive heart failure NYHA classification of ≥3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to start of treatment
  • Left ventricular ejection fraction (LVEF) <50 %
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  • Congenital long QT prolongation syndrome
  • Mean resting corrected QT interval (QTcF) >470 msec
  • Leptomeningeal carcinomatosis
  • Presence or history of uncontrolled or symptomatic brain metastases
  • Known pre-existing interstitial lung disease
  • Known active hepatitis B infection (defined as presence of Hep B sAg and/or Hep B Deoxyribonucleic acid (DNA)), active hepatitis C infection (defined as presence of Hep C Ribonucleic acid (RNA))
  • Active infectious disease
  • Any history or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of the trial drug
  • History of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED)
  • Further exclusion criteria apply
  • Combination part
  • Hypersensitivity to any of the excipients listed in the current Summary of Product Characteristics (SmPC)/Package insert (PI) of trametinib

Trial locations and contacts

8 sites in 3 countries.

8 sites in 3 countries

United States4 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Sarah Cannon Research Institute-Nashville-48456

    Nashville, Tennessee, 37203

Other trials in United States

Germany2 sites

  • Universitätsklinikum Köln (AöR)

    Cologne, 50937

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, 60590

Other trials in Germany

Netherlands2 sites

  • Erasmus Medisch Centrum-ROTTERDAM-50697

    Rotterdam, 3015 GD

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

About this study

Official title: A Phase I Open-label Dose Escalation Trial of BI 1701963 as Monotherapy and in Combination With Trametinib in Patients With KRAS Mutated Advanced or Metastatic Solid Tumours

This is a study in adults with advanced cancer (solid tumours) in whom previous chemotherapy was not successful. Only people who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes cancer grow faster.

The study tests 2 medicines called BI 1701963 and trametinib. BI 1701963 prevents reactivation of KRAS. In this study, BI 1701963 is given to humans for the first time. Trametinib is an approved medicine (MEK inhibitor).

Read more

The purpose of this study is to find out the highest dose of BI 1701963 alone and in combination with trametinib the participants can tolerate. Another purpose is to check whether BI 1701963 in combination with trametinib is able to make tumours shrink.

Participants can stay in the study as long as they benefit from treatment and can tolerate it.

During this time, they get tablets of BI 1701963 and trametinib once daily. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participants' health.

Being tested
BI 1701963, Trametinib
Keywords
SOS1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04111458
Study groupRoleWhat they receive
BI 1701963 monotherapyExperimentalNot described
Receives: Drug: BI 1701963
BI 1701963 + TrametinibExperimentalNot described
Receives: Drug: BI 1701963; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose escalation (Part A) - Maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs)

    Measured: 4 weeks

  2. Dose confirmation (Part B) - Number of patients with DLTs during the on-treatment period

    Measured: Up to 3 years

  3. Dose confirmation (Part B) and expansion (Part C) - Objective response

    Measured: Up to 3 years

Secondary outcomes (13)

  1. Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)

    Measured: Up to 5 weeks

  2. Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)

    Measured: Up to 5 weeks

  3. Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: Cmax (maximum measured concentration of the analyte in plasma)

    Measured: Up to 5 weeks

  4. Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: AUCτ (area under the concentration-time curve over a uniform dosing interval τ)

    Measured: Up to 5 weeks

  5. Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma)

    Measured: Up to 5 weeks

  6. Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)

    Measured: Up to 5 weeks

  7. Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: Cmax (maximum measured concentration of the analyte in plasma)

    Measured: Up to 5 weeks

  8. Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)

    Measured: Up to 5 weeks

  9. Dose confirmation (Part B) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period

    Measured: Up to 3 years

  10. Dose confirmation (Part B) and expansion (Part C) - Duration of Objective response (OR)

    Measured: Up to 3 years

  11. Dose confirmation (Part B) and expansion (Part C) - Tumour shrinkage (in millimetres)

    Measured: Up to 3 years

  12. Dose confirmation (Part B) and expansion (Part C) - Progression-free survival

    Measured: 6 months

  13. Dose confirmation (Part B) and expansion (Part C) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2019
  2. Study start4 Nov 2019
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

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
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04111458
Sponsor's protocol ID
1432-0001
Other IDs
2018-004757-24, 2018
Status last verified
Sep 2026
First submitted
27 Sep 2019
Last updated
29 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

Publications

  • Janne PA, Johnson ML, Li J, Pant S, Dunzinger U, Ilia L, Moldner K, Soh JE, Yamamoto N. The SOS1 Inhibitor BI 1701963 as Monotherapy or in Combination with Trametinib in Patients with KRAS Mutation-Positive Solid Tumors. Clin Cancer Res. 2026 Aug 3;32(15):3135-3145. doi: 10.1158/1078-0432.CCR-25-3725.

    PubMed 42048384

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI 1701963 and Trametinib in people with Solid Tumors, KRAS Mutation; SOS1, run by Boehringer Ingelheim at 8 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose escalation (Part A) - Maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs) (time frame: 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04111458, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.

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