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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LNP3794 | Experimental | Participants will receive LNP3794 orally once daily at different doses in 28 day cycles on a continuous basis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LNP3794 | Drug | LNP3794 capsules administered orally once daily |
|
| 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 |
| 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) |
| 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) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dhanajay Bakhle, MD | Lupin Limited | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cliniques universitaires Saint-Luc | Brussels | 1200 Bruxelles | Belgium | |||
| Amsterdam UMC |
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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 |
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 |
| Amsterdam |
| 1081 HV |
| Netherlands |
| Sarah Cannon Research Institute | London | W1G 6AD | United Kingdom |
| The Christie NHS Foundation | Manchester | M20 4BX | United Kingdom |