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)

NCT04111458 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 1432-00012018-004757-24
• Study Type: interventional
• Target: 71
• Locations: 3 countries
• Sites: 8

Brief 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. 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). 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.

Conditions

Solid Tumors, KRAS Mutation; SOS1

Keywords

SOS1

Outcome Measures

Primary Outcomes (3)

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

  4 weeks

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

  Up to 3 years

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

  Up to 3 years

Secondary Outcomes (13)

• 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)

  Up to 5 weeks

• 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)

  Up to 5 weeks

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

  Up to 5 weeks

• 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)

  Up to 5 weeks

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

  Up to 5 weeks

Study Arms (2)

BI 1701963 monotherapy

EXPERIMENTAL

Drug: BI 1701963

BI 1701963 + Trametinib

EXPERIMENTAL

Drug: BI 1701963; Drug: Trametinib

Interventions

Trametinib DRUG

Tablet

BI 1701963 + Trametinib

BI 1701963 DRUG

Tablet

BI 1701963 + Trametinib; BI 1701963 monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• 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

You may not qualify if:

• 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 %
• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (8)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Sarah Cannon Research Institute-Nashville-48456

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Universitätsklinikum Köln (AöR)

Cologne, 50937, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, 60590, Germany

Location

Erasmus Medisch Centrum-ROTTERDAM-50697

Rotterdam, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Links

• Related Info

MeSH Terms

Interventions

trametinib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: October 1, 2019
• Study Start: November 4, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor'

Locations

DE (2); US (4); NL (2)