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

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: Completed
• Conditions: NRAS/KRAS Mutated Advanced or Metastatic Refractory Solid Tumors
• Intervention / Treatment: Drug: LNP3794

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in pERK levels	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)	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

• Sponsor: Lupin Ltd.
• Investigators: Study Chair: Dhanajay Bakhle, MD, Lupin Limited

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2020
• Primary Completion (Actual): February 23, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: December 8, 2021
• First Submitted That Met QC Criteria: December 24, 2021
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 16, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID 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