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

Phase 1

Completed

• Conditions: NRAS/KRAS Mutated Advanced or Metastatic Refractory Solid Tumors
• Interventions: Drug: LNP3794

• Registration Number: NCT05187858
• Lead Sponsor: Lupin Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-22
• Study First Submitted: 2021-12-08
• Study First Submitted QC: 2021-12-24
• Study First Posted: 2022-01-12
• Primary Completion: 2022-02-23
• Study Completion: 2022-06-30
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-16
• Last Update Posted: 2023-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LNP3794	LNP3794	Participants will receive LNP3794 orally once daily at different doses in 28 day cycles on a continuous basis

Primary Outcome Measures

Name	Time	Method
Number of subjects with dose limiting toxicities (DLTs) at each dose level during the first cycle	up to Day 28	Dose limiting toxicities will be evaluated through the first cycle (each cycle is 28 days)

Secondary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax) of LNP3794	Cycle 1 (each cycle is 28 days) Day 1 and Day 14	Cmax is the maximum observed plasma concentration.
Area under the concentration-time curve from time zero to the end of dosing interval (AUC[0-tau])	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.
Time to maximum concentration (Tmax)	Cycle 1 (each cycle is 28 days) Day 1 and Day 14	Tmax is the time to reach maximum plasma concentration.
Number of subjects with DLTs during the entire on-treatment period	up to 2 years	Dose limiting toxicities will be evaluated through the entire on-treatment period
Number of subjects with Grade ≥3 treatment-related adverse events (AEs)	up to 2 years	Grade ≥3 treatment-related adverse events will be evaluated through the entire on-treatment period
Number of subjects with treatment-related AEs at each dose level	up to 2 years	Treatment-related AEs at each dose level will be evaluated through the entire on-treatment period
Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last])	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.

Trial Locations

Locations (4)

Cliniques universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

Sarah Cannon Research Institute; 🇬🇧 London, United Kingdom

The Christie NHS Foundation; 🇬🇧 Manchester, United Kingdom