A Study of LNP3794 in Subjects With NRAS/KRAS Mutated Advanced or Metastatic Refractory Solid Tumors

March 16, 2023 updated by: Lupin Ltd.

A Phase I Open-Label Study of LNP3794 (BI3011441) in Subjects With NRAS/KRAS Mutated Advanced or Metastatic Refractory Solid Tumors

This is a Phase I, open-label, dose escalation study of LNP3794 (BI3011441) in subjects with NRAS/KRAS mutated advanced or metastatic refractory solid tumors. The purpose of this study is to evaluate the safety/tolerability, pharmacokinetic and pharmacodynamic profile of the orally administered LNP3794 (BI3011441) as monotherapy at selected dose levels.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1200 Bruxelles
        • Cliniques universitaires Saint-Luc
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Amsterdam UMC
  • United Kingdom
      • London, United Kingdom, W1G 6AD
        • Sarah Cannon Research Institute
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Subjects ≥18 years of age
  2. Pathologically documented, locally-advanced or metastatic solid malignancy with NRAS or KRAS mutation
  3. At least one target lesion that can be measured per RECIST version 1.1
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
  6. Documented disease progression despite appropriate prior standard therapies or subjects for whom no standard therapy exists for their tumor type and disease stage
  7. Reproductive criteria (as defined in the protocol)

Exclusion Criteria:

  1. Subjects with symptomatic central nervous system (CNS) metastases
  2. History of another primary malignancy, with the exception of locally excised nonmelanoma skin cancer and carcinoma in situ of uterine cervix
  3. Known active hepatitis B infection or hepatitis C infection
  4. Known pre-existing interstitial lung disease
  5. Known diagnosis of human immunodeficiency virus (HIV) infection
  6. History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy; or known risk factors for RVO or central serous retinopathy
  7. Any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the Investigator, Sponsor, or contract research organization, could affect the subject's participation in the study
  8. Impaired cardiac function or clinically significant cardiac diseases
  9. Previous treatment with RAS or MEK targeting agents
  10. Chemotherapy, biologic therapy, immunotherapy, radiotherapy, or investigational agents within 5 half-lives or within 4 weeks (whichever is longer) prior to administration of the first dose of study treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LNP3794
Participants will receive LNP3794 orally once daily at different doses in 28 day cycles on a continuous basis
Drug: LNP3794
LNP3794 capsules administered orally once daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of subjects with dose limiting toxicities (DLTs) at each dose level during the first cycle
Time Frame: up to Day 28
Dose limiting toxicities will be evaluated through the first cycle (each cycle is 28 days)
up to Day 28

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of subjects with DLTs during the entire on-treatment period
Time Frame: up to 2 years
Dose limiting toxicities will be evaluated through the entire on-treatment period
up to 2 years
Number of subjects with Grade ≥3 treatment-related adverse events (AEs)
Time Frame: up to 2 years
Grade ≥3 treatment-related adverse events will be evaluated through the entire on-treatment period
up to 2 years
Number of subjects with treatment-related AEs at each dose level
Time Frame: up to 2 years
Treatment-related AEs at each dose level will be evaluated through the entire on-treatment period
up to 2 years
Maximum Plasma Concentration (Cmax) of LNP3794
Time Frame: Cycle 1 (each cycle is 28 days) Day 1 and Day 14
Cmax is the maximum observed plasma concentration.
Cycle 1 (each cycle is 28 days) Day 1 and Day 14
Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last])
Time Frame: Cycle 1 (each cycle is 28 days) Day 1 and Day 14
AUC[0-last] is the measure of plasma drug concentration from time zero to the time of last quantifiable concentration.
Cycle 1 (each cycle is 28 days) Day 1 and Day 14
Area under the concentration-time curve from time zero to the end of dosing interval (AUC[0-tau])
Time Frame: Cycle 1 (each cycle is 28 days) Day 1 to 2 and Day 14 to 15
AUC[0-tau] is the measure of plasma drug concentration from time zero to the end of dosing interval.
Cycle 1 (each cycle is 28 days) Day 1 to 2 and Day 14 to 15
Time to maximum concentration (Tmax)
Time Frame: Cycle 1 (each cycle is 28 days) Day 1 and Day 14
Tmax is the time to reach maximum plasma concentration.
Cycle 1 (each cycle is 28 days) Day 1 and Day 14

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline in pERK levels
Time Frame: Baseline and Cycle 1 (each cycle is 28 days) Day 14
Change from baseline in pERK levels will be evaluated
Baseline and Cycle 1 (each cycle is 28 days) Day 14
Objective response rate (ORR) and disease control rate (DCR)
Time Frame: up to 2 years
Objective response rate (ORR) and disease control rate (DCR) will be determined using response evaluation criteria in solid tumors (RECIST) v1.1.
up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lupin Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Dhanajay Bakhle, MD, Lupin Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 22, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 23, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 8, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 24, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 12, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 17, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LRP/LNP3794/2020/001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings