Adult and adolescent patients with advanced solid tumors harboring MAPK pathway alterations MedDRA version: 20.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Interventions
Product Code: LTT462
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: not established
Current Sponsor code: LTT462
Other descriptive name: LTT462
Concentration unit: mg milligram(s)
Concentrati
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient (male or female) =12 years of age - ECOG (Eastern Cooperative Oncology Group) performance status =1 - Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate. - Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy. Patients must be willing to undergo a new tumor biopsy at screening/baseline and during therapy. - Presence of at least one measurable lesion according to RECIST v1.1. - Documented MAPK Pathway alteration. Other protocol-defined inclusion criteria may apply. Are the trial subjects under 18? yes Number of subjects for this age range: 2 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: - Prior treatment with ERK inhibitors. - History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO. - Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures. - Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start of study treatment and for the duration of the study. - Clinically significant cardiac disease. Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize safety and tolerability of LTT462 and identify a recommended dose and regimen for future studies in adult and adolescent patients with advanced solid tumors harboring MAPK pathway alterations.;Secondary Objective: - To evaluate the preliminary anti-tumor activity of LTT462 - To evaluate the pharmacokinetic (PK) profile of LTT462 - To assess the pharmacodynamic (PD) effect of LTT462 ;Primary end point(s): - Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity. - Incidence and nature of dose limiting toxicities (DLTs) (dose escalation only);Timepoint(s) of evaluation of this end point: - Cycle 1 Day 1 until 30 days post study treatment (expected duration approximately 12 months) - 1 cycle (28 days). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • For both parts: - Overall response rate (ORR), Disease Control Rate (DCR), Duration of Response (DOR), and Progression Free Survival (PFS). - Plasma concentrations and derived PK parameters of LTT462 (AuC, Cmax, Tmax and T1/2). • For dose expansion part only: - Overall survival (OS) - Changes from baseline of the PD marker DUSP6 in tumor tissue and in blood. Plasma concentrations and derived PK parameters of LTT462 Changes from baseline of the PD marker DUSP6 in tumor tissue and in blood.;Timepoint(s) of evaluation of this end point: At protocol-defined timepoints (PK, PD and preliminary anti-tumor activity endpoint) until the end of study | — |
Countries
France, Germany, Italy, Japan, Netherlands, Singapore, Spain, Switzerland, United States
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed