Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Ovarian Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

LTT462

Novartis Pharmaceuticals

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

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

A Phase I Dose Finding Study of Oral LTT462 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations.

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.

Percentage of participants with dose limiting toxicity were reported.

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

Percentage of participants with at least dose interruptions were reported.

Dose intensity of LTT462 received by treatment group was reported.

Percentage of participants with overall response rate were reported.

Percentage of participants with disease control rate were reported.

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.

Median time for progression free survival was reported.

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

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.

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

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

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

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

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.

The Safety Set included all participants who had received at least one dose of LTT462.

Participants received 45 mg LTT462 QD as oral capsules.

LTT462 45 mg QD

Participants received 100 mg LTT462 QD as oral capsules.

LTT462 100 mg QD

Participants received 150 mg LTT462 QD as oral capsules.

LTT462 150 mg QD

Participants received 200 mg LTT462 QD as oral capsules.

LTT462 200 mg QD

Participants received 300 mg LTT462 QD as oral capsules.

LTT462 300 mg QD

Participants received 400 mg LTT462 QD as oral capsules.

LTT462 400 mg QD

Participants received 450 mg LTT462 QD as oral capsules.

LTT462 450 mg QD

LTT462 600 mg QD

Participants received 45 to 600 mg LTT462 QD as oral capsules.

All QD Participants

Participants received 150 mg LTT462 BID as oral capsules.

LTT462 150 mg BID

Participants received 200 mg LTT462 BID as oral capsules.

LTT462 200 mg BID

Participants received 150 and 200 mg LTT462 BID as oral capsules.

All BID Participants

Participants received 45 mg LTT462 once QD as oral capsules.

Participants received 600 mg LTT462 QD as oral capsules.

Total

Age, Categorical

Sex: Female, Male

Caucasian

Black

Asian

Unknown

Race/Ethnicity, Customized

Following careful evaluation of the available study data and considering the limited clinical activity observed with LTT462, the decision was made to not open the dose expansion phase of the study and the study was terminated early.

Study Director

SAEs

The safety set included all participants who had received at least one dose of LTT462.

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

The dose determining set included all participants from the safety set enrolled in the escalation part of the study who, during the first 28 days of dosing, had received at least 75 percent of the planned daily doses of LTT462 and had had sufficient safety evaluations, or had experienced a DLT.

Percentage of Participants With Dose Limiting Toxicities (DLTs)

Participants received 150 mg LTT462 twice daily (BID) as oral capsules.

Percentage of Participants With at Least One Dose Reduction

Percentage of Participants With at Least One Dose Interruptions

Dose Intensity Received by Participants

The full analysis set included all participants who had received at least one dose of LTT462.

Percentage of Participants With Overall Response Rate (ORR)

Percentage of Participants With Disease Control Rate (DCR)

As there were no participant achieving response (CR or PR) during escalation phase of the study (only stable disease was achieved). Therefore the evaluation of duration of response could not be performed.

Duration of Response (DOR)

Participants received 150 mg LTT462 twice daily (BID) as oral capsules

Progression Free Survival (PFS)

Overall survival was not evaluated because the study ended before enrolling into the dose-expansion part.

Overall Survival (OS) - Only for Dose Expansion Phase

Day 1

Day 15

Pharmacokinetic (PK) analysis set (PAS) included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'n' number analyzed signifies number of participants who were evaluable at each time point.

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

PAS included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'N' number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

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

PAS included of all participants who have at least 1 PK blood sample providing measurable LTT462 and received at least 1 dose of study drug, didn't vomit within 4 hours postdose, had at least 1 primary PK parameter. Here 'n' number analyzed signifies number of participants who were evaluable at each time point.

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

Elimination Half-life (T1/2) of LTT462

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

Accumulation Ratio (Racc) of LTT462

Tumor Sample

Blood Sample

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

Participants received LTT462 45 milligram (mg) once daily (QD)

Spots Global Cancer Trial Database for A Phase I Clinical Study With Investigational Compound LTT462 in Adult Patients With Specific Advanced Cancers.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial