A Phase I Clinical Study With Investigational Compound LTT462 in Adult Patients With Specific Advanced Cancers.

Phase 1TerminatedNCT02711345

Novartis Pharmaceuticals65 enrolled

Overview

A phase I study of LTT462 in patients with advanced solid tumors that harbor MAPK pathway alterations.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ovarian Neoplasms Non-Small-Cell Lung Carcinoma Melanoma Other Solid Tumors

Interventions

LTT462DRUG

ERK Inhibitor

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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 be willing and able to undergo study required biopsies. * Presence of at least one measurable lesion according to RECIST v1.1. * Documented MAPK pathway alteration 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 study treatment and for the duration of the study. * Patients with malignant disease other than that being treated in the study. * Clinically significant cardiac disease. Other protocol-defined exclusion criteria may apply.

Locations (7)

Novartis Investigative Site

New York, New York, United States

Novartis Investigative Site

Houston, Texas, United States

Novartis Investigative Site

Essen, Germany

Novartis Investigative Site

Chuo Ku, Tokyo, Japan

Outcomes

Primary Outcomes

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An adverse events is defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occur after participant's signed informed consent has been obtained. A SAE is described as any adverse event that leads to death, is life threatening, causes or prolongs hospitalization, results in a congenital anomaly, or any other important medical event not described above.

Time frame: Up to 2.8 years

Percentage of Participants With Dose Limiting Toxicities (DLTs)

Percentage of participants with dose limiting toxicity were reported.

Time frame: Up to 2.8 years

Percentage of Participants With at Least One Dose Reduction

Percentage of participants with at least one dose reduction were reported.

Time frame: Up to 2.8 years

Percentage of Participants With at Least One Dose Interruptions

Percentage of participants with at least dose interruptions were reported.

Time frame: Up to 2.8 years

Dose Intensity Received by Participants

Dose intensity of LTT462 received by treatment group was reported.

Time frame: Up to 2.8 years

Secondary Outcomes

Percentage of Participants With Overall Response Rate (ORR)

Percentage of participants with overall response rate were reported.

Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

Percentage of Participants With Disease Control Rate (DCR)

Data from ClinicalTrials.gov

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Novartis Investigative Site

Singapore, Singapore

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Bellinzona, Switzerland

Percentage of participants with disease control rate were reported.

Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

Duration of Response (DOR)

DOR is defined as the time between the date of the first documented response (complete response \[CR\] or partial response \[PR\]) and the date of progression.

Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

Progression Free Survival (PFS)

Median time for progression free survival was reported.

Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

Overall Survival (OS) - Only for Dose Expansion Phase

Median time for overall survival, only for dose expansion phase was reported.

Time frame: Every 2 cycles after starting LTT462 treatment until end of treatment (Up to 2.8 years)

The Maximum (Peak) Observed Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Cmax) After Single Dose Administration of LTT462

Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration expressed in mass x volume-1.

Time frame: day 1, day 15

Area Under the Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LTT462

AUClast is the area under the curve from time zero to the last measurable concentration sampling time calculated by mass \* time \*volume\^-1

Time frame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1

The Time to Reach Maximum (Peak) Plasma, Blood, Serum, or Other Body Fluid Drug Concentration (Tmax) After Single Dose Administration of LTT462

Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration.

Time frame: day 1, day 15

Elimination Half-life (T1/2) of LTT462

T1/2 is the Elimination half-life.

Time frame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1

The Area Under the Curve Calculated to the End of a Dosing Interval (Tau) at Steady-state (AUCtau) of LTT462

AUCtau is the area under the curve calculated to the end of a dosing interval (tau) at steady-state calculated by formula amount \*time \* volume\^-1

Time frame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1

Accumulation Ratio (Racc) of LTT462

Racc is the accumulation ratio calculated by AUCtau ratio Day 15 versus Day 1.

Time frame: Cycle 1 Days 1, 2, 3, 8, 15 and 16; Cycle 2 day 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1

Changes From Baseline in Relative Quantity (RQ) of Dual Specificity Phosphatase 6 (DUSP6) in Tumor Tissue and in Blood

Assessment of Pharmacodynamic (PD) effects of LTT462 in tumor, pre- and post- treatment tumor biopsies were examined for expression of DUSP6. For assessment of PD effects in blood, levels of DUSP6 were measured in blood samples.

Time frame: Cycle 1 Days 1, 2, 3, 15 and 16