Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Channel Blockers

Herbal and Botanical

Tislelizumab

Trametinib

Dabrafenib

Spartalizumab

Gallopamil

Naporafenib

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

Immune Checkpoint Inhibitors

Cola

dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer

dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.

LTT462

LXH254

TNO155

Liquid in vial (Concentrate for solution for infusion) for intravenous use

Novartis Pharmaceuticals

A phase Ib, open-label platform study of select drug combinations chosen in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies.

This is a phase Ib, multi-center, open-label study with multiple treatment arms in adult patients with advanced or metastatic BRAF V600 (E, D, or K) in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies. The open platform design of this study is adaptive to allow removal of combination treatment arm(s) based on emerging data and facilitate introduction of new candidate combinations. The study is comprised of a dose escalation part and may be followed by a dose expansion part for any combination treatment arm.

A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer

A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Drug Combinations in Adult Patients With Advanced or Metastatic BRAF V600 Colorectal Cancer

To characterize safety and tolerability of each treatment arm tested and identify recommended doses (RD) and regimens for future studies

To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies

To characterize the PK of each investigational drug within each treatment arm

To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.

To evaluate PD effect in their respective combinations in tumor

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

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)

Overall Study

Symptoms and General Pathology

Adenocarcinoma

Neoplasm Metastasis

Adenocarcinoma of Lung

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Lung Adenocarcinoma

Neuroendocrine Tumor

Neuroepithelioma

LXH254 will be supplied as tablet for oral use.

LTT462 will be supplied as hard gelatin capsule for oral use.

Trametinib will be supplied as film-coated tablet for oral use

Ribociclib will be supplied in tablets and hard gelatin capsules.

Ribociclib

To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.

A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma

A Phase Ib, Open-label, Multicenter Study of Oral LXH254-centric Combinations in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer or NRAS Mutant Melanoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer	NCT04294160	BRAF V600 Color...	Dabrafenib LTT462 Trametinib LXH254 TNO155 Spartalizumab Tislelizumab	18 Years -	Novartis
A Phase I Clinical Study With Investigational Compound LTT462 in Adult Patients With Specific Advanced Cancers.	NCT02711345	Ovarian Neoplas... Non-Small-Cell ... Melanoma Other Solid Tum...	LTT462	12 Years -	Novartis
A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma	NCT02974725	Non-Small Cell ... Melanoma	LXH254 LTT462 Trametinib Ribociclib	18 Years -	Novartis
A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma	NCT02974725	Non-Small Cell ... Melanoma	LXH254 LTT462 Trametinib Ribociclib	18 Years -	Novartis

Spots Global Cancer Trial Database for ltt462

Every month we try and update this database with for ltt462 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ltt462

Every month we try and update this database with for ltt462 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ltt462 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.