Solid Tumors, KRAS MutationPhase 1NCT04835714
A Study to Find a Safe and Effective Dose of BI 1701963 Alone and in Combination With BI 3011441 in Patients With Advanced Cancer and a Certain Mutation (Kirsten Rat Sarcoma Viral Oncogene Homologue [KRAS])
A Phase 1 study testing BI 1701963 and BI 3011441 in people with Solid Tumors, KRAS Mutation, run by Boehringer Ingelheim at 4 sites in Japan.
Trial summary
This is a study in adults with advanced cancer (solid tumours including non-small cell lung cancer and colorectal cancer) in whom previous chemotherapy was not successful. People who have a tumour with a KRAS mutation can participate in the study. A KRAS mutation makes cancer grow faster. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, KRAS Mutation
- What is being tested?
- BI 1701963 and BI 3011441
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 4 sitesJapan
- Study dates
- 20 Apr 2021to 18 Jan 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Previously-identified activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation in tumour tissue or blood prior to screening. Activating mutations may include but are not limited to: KRAS mutations in expressed region (exon) 2 (G12, G13), exon 3 (A59, Q61) and exon 4 (K117, A146).
- Provision of archival tumour tissue, if available, to confirm retrospectively KRAS mutation status and for biomarker assessment
- At least one target lesion that can be measured per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. In patients who only have one target lesion, and a biopsy of the lesion is required, the baseline imaging must be performed at the earliest two weeks after the biopsy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
- Adequate organ function at screening as follows:
- Absolute neutrophil count (ANC) ≥1.5 x 109/L; hemoglobin ≥9.0 g/dL; platelets ≥100 x 109/L without the use of haematopoietic growth factors or recent transfusion
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- Total bilirubin ≤1.5 times the upper limit of normal (ULN), or ≤4 x ULN for patients who are known to have Gilbert's syndrome.
- Creatinine ≤1.5 x ULN. If creatinine is >1.5 x ULN, patient is eligible if concurrent glomerular filtration rate (GFR) ≥50 mL/min (measured or calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula).
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 x ULN if no demonstrable liver metastases, or ≤ 5 x ULN if transaminase elevation is attributable to liver metastases.
- Age ≥18 years of age, or over the legal age of consent as required by local legislation at informed consent.
- Recovery from any previous therapy related toxicity to Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤1 at Cycle 1 Day 1 (except for alopecia, stable sensory neuropathy must be CTCAE Grade ≤2 and except for amenorrhea/menstruation related disorders of any grade) before the first dose.
- Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to admission to the trial.
- Further inclusion criteria apply.
Who cannot join
- Previous anticancer chemotherapy or anticancer immunotherapy within 3 weeks of the first administration of trial drug. Previous anticancer hormonal treatment within 2 weeks of the first administration of trial drugs.
- Previous treatment with Rat sarcoma (RAS), Mitogen-activated protein kinase (MAPK) or Son of Sevenless 1 (SOS1) targeting agents
- Radiotherapy within 4 weeks prior to start of treatment except as follows
- Palliative radiotherapy to regions other than the chest is allowed up to 2 weeks prior to start of treatment
- Single dose palliative radiotherapy for symptomatic metastasis within 2 weeks prior to start of treatment may be allowed but must be discussed with the sponsor.
- Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to start of treatment or planned during the projected course of the trial, e.g. hip replacement.
Show all 10Show fewer
- Previous treatment with any investigational agent(s) or targeted treatment within 28 days prior to start of treatment.
- Known history of hypersensitivity to any of the excipients of BI 1701963 tablets
- History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New-York-Heart-Assocation (NYHA) classification of ≥3, unstable angina or poorly controlled arrhythmia which are considered clinically relevant by the investigator; myocardial infarction within 6 months prior to start of treatment. Uncontrolled hypertension is defined as: Blood pressure (BP) measured in a rested and relaxed condition, where systolic BP ≥140 mmHg, or diastolic BP ≥90 mmHg, with or without medication.
- Left ventricular ejection fraction (LVEF) <50 %. Further exclusion criteria apply.
Trial locations and contacts
4 sites in 1 country.
Japan4 sites
Aichi Cancer Center Hospital
Aichi, Nagoya, 464-8681
National Cancer Center Hospital East
Chiba, Kashiwa, 277-8577
National Cancer Center Hospital
Tokyo, Chuo-ku, 104-0045
Japanese Foundation for Cancer Research
Tokyo, Koto-ku, 135-8550
About this study
Official title: A Phase I Open-label Dose Escalation Trial of BI 1701963 as Monotherapy and in Combination With BI 3011441 in Patients With KRAS Mutated Advanced or Metastatic Solid Tumours
This is a study in adults with advanced cancer (solid tumours including non-small cell lung cancer and colorectal cancer) in whom previous chemotherapy was not successful. 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 BI 3011441. BI 1701963 and BI 3011441 prevent activation of KRAS.
Read more
The purpose of this study is to find out the highest dose of BI 1701963 alone and in combination with BI 3011441 the participants can tolerate. Another purpose is to check whether BI 1701963 in combination with BI 3011441 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 capsules of BI 3011441 once daily. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participants' health.
- Conditions
- Solid Tumors, KRAS Mutation
- Being tested
- BI 1701963, BI 3011441
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 1701963Drug
BI 1701963
BI 3011441Drug
BI 3011441
| Study group | Role | What they receive |
|---|---|---|
| Part A with Monotherapy dose escalation | Experimental | Not described Receives: Drug: BI 1701963 |
| Part B with Combination therapy dose escalation | Experimental | Not described Receives: Drug: BI 1701963; Drug: BI 3011441 |
| Part C with Combination therapy dose confirmation | Experimental | Not described Receives: Drug: BI 1701963; Drug: BI 3011441 |
| Part D with Combination therapy dose expansion | Experimental | Not described Receives: Drug: BI 1701963; Drug: BI 3011441 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with dose-limiting toxicities (DLTs) in the Maximum tolerated dose (MTD) evaluation period in monotherapy (Part A)
Measured: Up to 28 days
Number of patients with dose-limiting toxicities (DLTs) in the Maximum tolerated dose (MTD) evaluation period in combination therapy (Part B)
Measured: Up to 28 days
Objective response (OR) defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) in combination therapy dose confirmation (Part C)
Best overall response is defined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 as assessed by the investigator and will consider all tumour assessments from first administration until disease progression or death (whichever occurs first) or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent.
Measured: Up to 12 months
Objective response (OR) defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) in combination therapy dose expansion (Part D)
Best overall response is defined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 as assessed by the investigator and will consider all tumour assessments from first administration until disease progression or death (whichever occurs first) or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent.
Measured: Up to 12 months
Secondary outcomes (36)
Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in monotherapy (Part A)
Measured: Up to 24 hours
Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in combination therapy (Part B)
Measured: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in monotherapy (Part A)
Measured: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in combination therapy (Part B)
Measured: Up to 24 hours
Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in monotherapy (Part A)
Measured: Up to 12 weeks
Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in combination therapy (Part B)
Measured: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in monotherapy (Part A)
Measured: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in combination therapy (Part B)
Measured: Up to 12 weeks
Maximum plasma concentration (Cmax) of BI 3011441 after the first dose (Part B only)
Measured: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 3011441 after the first dose (Part B only)
Measured: Up to 24 hours
Maximum plasma concentration at steady state (Cmax,ss) of BI 3011441 after multiple doses (Part B only)
Measured: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 3011441 after multiple doses (Part B only)
Measured: Up to 12 weeks
Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 treatment-related adverse events observed during the on-treatment period in combination therapy dose confirmation (Part C)
Measured: Up to 12 months
Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 treatment-related adverse events observed during the on-treatment period in combination therapy dose expansion (Part D)
Measured: Up to 12 months
Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in combination therapy dose confirmation (Part C)
Measured: Up to 24 hours
Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in combination therapy dose expansion (Part D)
Measured: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in combination therapy dose confirmation (Part C)
Measured: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in combination therapy dose expansion (Part D)
Measured: Up to 24 hours
Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in combination therapy dose confirmation (Part C)
Measured: Up to 12 weeks
Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in combination therapy dose expansion (Part D)
Measured: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in combination therapy dose confirmation (Part C)
Measured: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in combination therapy dose expansion (Part D)
Measured: Up to 12 weeks
Maximum plasma concentration (Cmax) of BI 3011441 after the first dose in combination therapy dose confirmation (Part C)
Measured: Up to 24 hours
Maximum plasma concentration (Cmax) of BI 3011441 after the first dose in combination therapy dose expansion (Part D)
Measured: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 3011441 after the first dose in combination therapy dose confirmation (Part C)
Measured: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 3011441 after the first dose in combination therapy dose expansion (Part D)
Measured: Up to 24 hours
Maximum plasma concentration at steady state (Cmax,ss) of BI 3011441 after multiple doses in combination therapy dose confirmation (Part C)
Measured: Up to 12 weeks
Maximum plasma concentration at steady state (Cmax,ss) of BI 3011441 after multiple doses in combination therapy dose expansion (Part D)
Measured: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 3011441 after multiple doses in combination therapy dose confirmation (Part C)
Measured: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 3011441 after multiple doses in combination therapy dose expansion (Part D)
Measured: Up to 12 weeks
Duration of Objective Response (OR) in combination therapy dose confirmation (Part C)
Duration of OR is defined as the time from first documented CR or PR until disease progression or death (whichever occurs first) among patients with OR.
Measured: Up to 12 months
Duration of Objective Response (OR) in combination therapy dose expansion (Part D)
Duration of OR is defined as the time from first documented CR or PR until disease progression or death (whichever occurs first) among patients with OR.
Measured: Up to 12 months
Tumour shrinkage (in millimetres) in combination therapy dose confirmation (Part C)
Tumour shrinkage (in millimetres) is defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of longest diameters of the same set of target lesions.
Measured: Up to 12 months
Tumour shrinkage (in millimetres) in combination therapy dose expansion (Part D)
Tumour shrinkage (in millimetres) is defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of longest diameters of the same set of target lesions.
Measured: Up to 12 months
Progression-free survival (PFS) rate at 6 months in combination therapy dose confirmation (Part C)
Based on PFS defined as the time from first administration until tumour progression according to RECIST 1.1 or death from any cause, whichever occurs earlier
Measured: Up to 6 months
Progression-free survival (PFS) rate at 6 months in combination therapy dose expansion (Part D)
Based on PFS defined as the time from first administration until tumour progression according to RECIST 1.1 or death from any cause, whichever occurs earlier
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2021
- Study start20 Apr 2021
- Primary completion18 Jan 2022
- Study completion18 Jan 2022
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumors, KRAS MutationStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe 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
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04835714
- Sponsor's protocol ID
- 1432-0006
- Status last verified
- Jan 2023
- First submitted
- 6 Apr 2021
- Last updated
- 1 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing
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
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-label Dose Escalation Trial of BI 1701963 as Monotherapy and in Combination With BI 3011441 in Patients With KRAS Mutated Advanced or Metastatic Solid Tumours
- ClinicalTrials.gov ID
- NCT04835714
- Acronym / sponsor ID
- 1432-0006
- Conditions
- Solid Tumors, KRAS Mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 20 Apr 2021 (actual)
- Primary completion
- 18 Jan 2022 (actual)
- Study completion
- 18 Jan 2022 (actual)
- First posted
- 8 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study in adults with advanced cancer (solid tumours including non-small cell lung cancer and colorectal cancer) in whom previous chemotherapy was not successful. 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 BI 3011441. BI 1701963 and BI 3011441 prevent activation of KRAS.
The purpose of this study is to find out the highest dose of BI 1701963 alone and in combination with BI 3011441 the participants can tolerate. Another purpose is to check whether BI 1701963 in combination with BI 3011441 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 capsules of BI 3011441 once daily. The doctors regularly monitor the size of the tumour. Doctors also regularly record any unwanted effects and check participants' health.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A with Monotherapy dose escalation | Experimental | Drug: BI 1701963 |
| Part B with Combination therapy dose escalation | Experimental | Drug: BI 1701963, Drug: BI 3011441 |
| Part C with Combination therapy dose confirmation | Experimental | Drug: BI 1701963, Drug: BI 3011441 |
| Part D with Combination therapy dose expansion | Experimental | Drug: BI 1701963, Drug: BI 3011441 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Previously-identified activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation in tumour tissue or blood prior to screening. Activating mutations may include but are not limited to: KRAS mutations in expressed region (exon) 2 (G12, G13), exon 3 (A59, Q61) and exon 4 (K117, A146).
- Provision of archival tumour tissue, if available, to confirm retrospectively KRAS mutation status and for biomarker assessment
- At least one target lesion that can be measured per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. In patients who only have one target lesion, and a biopsy of the lesion is required, the baseline imaging must be performed at the earliest two weeks after the biopsy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
- Adequate organ function at screening as follows:
Key exclusion criteria (10 listed)
- Previous anticancer chemotherapy or anticancer immunotherapy within 3 weeks of the first administration of trial drug. Previous anticancer hormonal treatment within 2 weeks of the first administration of trial drugs.
- Previous treatment with Rat sarcoma (RAS), Mitogen-activated protein kinase (MAPK) or Son of Sevenless 1 (SOS1) targeting agents
- Radiotherapy within 4 weeks prior to start of treatment except as follows
- Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to start of treatment or planned during the projected course of the trial, e.g. hip replacement.
- Previous treatment with any investigational agent(s) or targeted treatment within 28 days prior to start of treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BI 1701963BI 1701963 | Drug | Part A with Monotherapy dose escalation, Part B with Combination therapy dose escalation, Part C with Combination therapy dose confirmation, Part D with Combination therapy dose expansion |
| BI 3011441BI 3011441 | Drug | Part B with Combination therapy dose escalation, Part C with Combination therapy dose confirmation, Part D with Combination therapy dose expansion |
Primary outcome
Number of patients with dose-limiting toxicities (DLTs) in the Maximum tolerated dose (MTD) evaluation period in monotherapy (Part A)
Time frame: Up to 28 days
Number of patients with dose-limiting toxicities (DLTs) in the Maximum tolerated dose (MTD) evaluation period in combination therapy (Part B)
Time frame: Up to 28 days
Objective response (OR) defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) in combination therapy dose confirmation (Part C)
Time frame: Up to 12 months
Best overall response is defined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 as assessed by the investigator and will consider all tumour assessments from first administration until disease progression or death (whichever occurs first) or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent.
Objective response (OR) defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) in combination therapy dose expansion (Part D)
Time frame: Up to 12 months
Best overall response is defined according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 as assessed by the investigator and will consider all tumour assessments from first administration until disease progression or death (whichever occurs first) or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent.
36 secondary outcomes
Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in monotherapy (Part A)
Time frame: Up to 24 hours
Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in combination therapy (Part B)
Time frame: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in monotherapy (Part A)
Time frame: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in combination therapy (Part B)
Time frame: Up to 24 hours
Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in monotherapy (Part A)
Time frame: Up to 12 weeks
Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in combination therapy (Part B)
Time frame: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in monotherapy (Part A)
Time frame: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in combination therapy (Part B)
Time frame: Up to 12 weeks
Maximum plasma concentration (Cmax) of BI 3011441 after the first dose (Part B only)
Time frame: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 3011441 after the first dose (Part B only)
Time frame: Up to 24 hours
Maximum plasma concentration at steady state (Cmax,ss) of BI 3011441 after multiple doses (Part B only)
Time frame: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 3011441 after multiple doses (Part B only)
Time frame: Up to 12 weeks
Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 treatment-related adverse events observed during the on-treatment period in combination therapy dose confirmation (Part C)
Time frame: Up to 12 months
Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 treatment-related adverse events observed during the on-treatment period in combination therapy dose expansion (Part D)
Time frame: Up to 12 months
Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in combination therapy dose confirmation (Part C)
Time frame: Up to 24 hours
Maximum plasma concentration (Cmax) of BI 1701963 after the first dose in combination therapy dose expansion (Part D)
Time frame: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in combination therapy dose confirmation (Part C)
Time frame: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 1701963 after the first dose in combination therapy dose expansion (Part D)
Time frame: Up to 24 hours
Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in combination therapy dose confirmation (Part C)
Time frame: Up to 12 weeks
Maximum plasma concentration at steady state (Cmax,ss) of BI 1701963 after multiple doses in combination therapy dose expansion (Part D)
Time frame: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in combination therapy dose confirmation (Part C)
Time frame: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 1701963 after multiple doses in combination therapy dose expansion (Part D)
Time frame: Up to 12 weeks
Maximum plasma concentration (Cmax) of BI 3011441 after the first dose in combination therapy dose confirmation (Part C)
Time frame: Up to 24 hours
Maximum plasma concentration (Cmax) of BI 3011441 after the first dose in combination therapy dose expansion (Part D)
Time frame: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 3011441 after the first dose in combination therapy dose confirmation (Part C)
Time frame: Up to 24 hours
Area under the plasma concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) of BI 3011441 after the first dose in combination therapy dose expansion (Part D)
Time frame: Up to 24 hours
Maximum plasma concentration at steady state (Cmax,ss) of BI 3011441 after multiple doses in combination therapy dose confirmation (Part C)
Time frame: Up to 12 weeks
Maximum plasma concentration at steady state (Cmax,ss) of BI 3011441 after multiple doses in combination therapy dose expansion (Part D)
Time frame: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 3011441 after multiple doses in combination therapy dose confirmation (Part C)
Time frame: Up to 12 weeks
Area under the concentration-time curve at steady state over the uniform dosing interval τ (AUCτ,ss) of BI 3011441 after multiple doses in combination therapy dose expansion (Part D)
Time frame: Up to 12 weeks
Duration of Objective Response (OR) in combination therapy dose confirmation (Part C)
Time frame: Up to 12 months
Duration of Objective Response (OR) in combination therapy dose expansion (Part D)
Time frame: Up to 12 months
Tumour shrinkage (in millimetres) in combination therapy dose confirmation (Part C)
Time frame: Up to 12 months
Tumour shrinkage (in millimetres) in combination therapy dose expansion (Part D)
Time frame: Up to 12 months
Progression-free survival (PFS) rate at 6 months in combination therapy dose confirmation (Part C)
Time frame: Up to 6 months
Progression-free survival (PFS) rate at 6 months in combination therapy dose expansion (Part D)
Time frame: Up to 6 months
Results and safety
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2023.
- Derived from this study: PubMed 42048384Janne 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 1701963 and BI 3011441 in people with Solid Tumors, KRAS Mutation, run by Boehringer Ingelheim at 4 sites in Japan.
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 13 inclusion and 10 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: stopped early, as of the sponsor's last update on 1 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Japan. 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?
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
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?
Number of patients with dose-limiting toxicities (DLTs) in the Maximum tolerated dose (MTD) evaluation period in monotherapy (Part A) (time frame: Up to 28 days). The study lists 4 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 NCT04835714, 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 1 Feb 2023.