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])

NCT ID: NCT04835714

Last Updated: 2023-02-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-20
• Study Completion Date: 2022-01-18

Brief 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.

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.

Conditions

Solid Tumors, KRAS Mutation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A with Monotherapy dose escalation

Group Type: EXPERIMENTAL

BI 1701963

Intervention Type: DRUG

BI 1701963

Part B with Combination therapy dose escalation

Group Type: EXPERIMENTAL

BI 1701963

Intervention Type: DRUG

BI 1701963

BI 3011441

Intervention Type: DRUG

BI 3011441

Part C with Combination therapy dose confirmation

Group Type: EXPERIMENTAL

BI 1701963

Intervention Type: DRUG

BI 1701963

BI 3011441

Intervention Type: DRUG

BI 3011441

Part D with Combination therapy dose expansion

Group Type: EXPERIMENTAL

BI 1701963

Intervention Type: DRUG

BI 1701963

BI 3011441

Intervention Type: DRUG

BI 3011441

Interventions

BI 1701963

BI 1701963

Intervention Type: DRUG

BI 3011441

BI 3011441

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Aichi Cancer Center Hospital

Aichi, Nagoya, , Japan

National Cancer Center Hospital East

Chiba, Kashiwa, , Japan

National Cancer Center Hospital

Tokyo, Chuo-ku, , Japan

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, , Japan

Countries

Japan

Related Links

https://www.mystudywindow.com/

Related Info

Other Identifiers

1432-0006

Identifier Type: -

Identifier Source: org_study_id