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

Study Overview
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Brief Summary
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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.

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

Conditions
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NRAS/KRAS Mutated Advanced or Metastatic Refractory Solid Tumors

Intervention / Treatment
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* Drug: LNP3794


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects ≥18 years of age Pathologically documented, locally-advanced or metastatic solid malignancy with NRAS or KRAS mutation At least one target lesion that can be measured per RECIST version 1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ function (bone marrow, hepatic, renal, cardiovascular) Documented disease progression despite appropriate prior standard therapies or subjects for whom no standard therapy exists for their tumor type and disease stage Reproductive criteria (as defined in the protocol) Exclusion Criteria: Subjects with symptomatic central nervous system (CNS) metastases History of another primary malignancy, with the exception of locally excised nonmelanoma skin cancer and carcinoma in situ of uterine cervix Known active hepatitis B infection or hepatitis C infection Known pre-existing interstitial lung disease Known diagnosis of human immunodeficiency virus (HIV) infection History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy; or known risk factors for RVO or central serous retinopathy 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 Impaired cardiac function or clinically significant cardiac diseases Previous treatment with RAS or MEK targeting agents 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LNP3794<br>Participants will receive LNP3794 orally once daily at different doses in 28 day cycles on a continuous basis | Drug: LNP3794<br>* LNP3794 capsules administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with dose limiting toxicities (DLTs) at each dose level during the first cycle | Dose limiting toxicities will be evaluated through the first cycle (each cycle is 28 days) | up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with DLTs during the entire on-treatment period | 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) | 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 | 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 | 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]) | 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]) | 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) | Tmax is the time to reach maximum plasma concentration. | Cycle 1 (each cycle is 28 days) Day 1 and Day 14 |