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

NCT05187858 | Completed Phase 1

• 1 other identifier: LRP/LNP3794/2020/001
• Study Type: interventional
• Target: 15
• Locations: 3 countries
• Sites: 4

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.

Conditions

NRAS/KRAS Mutated Advanced or Metastatic Refractory Solid Tumors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Number of subjects with DLTs during the entire on-treatment period

  up to 2 years

• Number of subjects with Grade ≥3 treatment-related adverse events (AEs)

  up to 2 years

• Number of subjects with treatment-related AEs at each dose level

  up to 2 years

• Maximum Plasma Concentration (Cmax) of LNP3794

  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])

  Cycle 1 (each cycle is 28 days) Day 1 and Day 14

Other Outcomes (2)

• Change from baseline in pERK levels

  Baseline and Cycle 1 (each cycle is 28 days) Day 14

• Objective response rate (ORR) and disease control rate (DCR)

  up to 2 years

Study Arms (1)

LNP3794

EXPERIMENTAL

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

Drug: LNP3794

Interventions

LNP3794 DRUG

LNP3794 capsules administered orally once daily

LNP3794

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Lupin Ltd.: lead

Study Sites (4)

Cliniques universitaires Saint-Luc

Brussels, 1200 Bruxelles, Belgium

Location

Amsterdam UMC

Amsterdam, 1081 HV, Netherlands

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

The Christie NHS Foundation

Manchester, M20 4BX, United Kingdom

Location

Study Officials

• Dhanajay Bakhle, MD

  Lupin Limited

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: January 12, 2022
• Study Start: September 22, 2020
• Primary Completion: February 23, 2022
• Study Completion: June 30, 2022
• Last Updated: March 17, 2023

Record last verified: 2023-03

Locations

GB (2); NL (1); BE (1)