Clinical trial NCT05187858: A Study of LNP3794 in Subjects With NRAS/KRAS Mutated Advanced or Metastatic Refractory Solid Tumors
Official title: A Phase I Open-Label Study of LNP3794 (BI3011441) in Subjects With NRAS/KRAS Mutated Advanced or Metastatic Refractory Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: NRAS/KRAS Mutated Advanced or Metastatic Refractory Solid Tumors
Lead sponsor: Lupin Ltd.
Sponsor class: INDUSTRY
First posted: 2022-01-12
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with dose limiting toxicities (DLTs) at each dose level during the first cycle
timeFrame: up to Day 28
Secondary outcomes:
measure: Number of subjects with DLTs during the entire on-treatment period
timeFrame: up to 2 years
measure: Number of subjects with Grade ≥3 treatment-related adverse events (AEs)
timeFrame: up to 2 years
measure: Number of subjects with treatment-related AEs at each dose level
timeFrame: up to 2 years
measure: Maximum Plasma Concentration (Cmax) of LNP3794
timeFrame: Cycle 1 (each cycle is 28 days) Day 1 and Day 14
measure: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last])
timeFrame: Cycle 1 (each cycle is 28 days) Day 1 and Day 14
measure: Area under the concentration-time curve from time zero to the end of dosing interval (AUC[0-tau])
timeFrame: Cycle 1 (each cycle is 28 days) Day 1 to 2 and Day 14 to 15
measure: Time to maximum concentration (Tmax)
timeFrame: Cycle 1 (each cycle is 28 days) Day 1 and Day 14
Other outcomes:
measure: Change from baseline in pERK levels
timeFrame: Baseline and Cycle 1 (each cycle is 28 days) Day 14
measure: Objective response rate (ORR) and disease control rate (DCR)
timeFrame: up to 2 years
Locations:
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation
Study officials:
affiliation: Lupin Limited
name: Dhanajay Bakhle, MD
role: STUDY_CHAIR
References: