Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Trametinib

Gefitinib

Nazartinib

Naporafenib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

EGF816 + INC280 in expansion phase (patients with no known resistance mechanism)

EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism)

EGF816 + LXH254 in expansion phase (patients with known resistance mechanism)

EGF816 + INC280 in expansion phase (patients with known resistance mechanism)

EGF816

trametinib

ribociclib

LXH254

INC280

gefitinib

Novartis Pharmaceuticals

The study purpose is to evaluate the safety, tolerability, and preliminary efficacy of the addition of INC280, trametinib, ribociclib, gefitinib, or LXH254 to EGF816 in adult patients with advanced EGFR-mutant NSCLC.

This is a Phase Ib, open label, non-randomized dose escalation study of EGF816 in combination with ribociclib, trametinib, or LXH254, followed by dose expansion of EGF816 in combination with ribociclib, trametinib, LXH254, INC280, or gefitinib in adult patients with advanced EGFR-mutant NSCLC.

During the dose escalation part, patients will be assigned to the addition of trametinib, ribociclib, or LXH254 to EGF816.

Following determination of the recommended dose for the combination of EGF816 + trametinib, EGF816 + ribociclib, and EGF816 + LXH254, patients may be enrolled to the dose expansion arms of each of these combinations. Patients may also be assigned to EGF816 + INC280 or EGF816 + gefitinib in dose expansion.

Efficacy assessments will be performed at baseline and every 2 cycles during treatment.

Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC

A Phase Ib, Open Label, Multi-center Study to Characterize the Safety, Tolerability and Preliminary Efficacy of EGF816 in Combination With Selected Targeted Agents in EGFR Mutant NSCLC

Assess safety and tolerability including incidence of dose limiting toxicities, adverse events, and serious adverse events.

Modified objective response rate (ORR2) per RECIST v1.1 (taking as baseline the most recent assessment prior to initiating combination)

Overall response rate (ORR) per RECIST v1.1

Time from the date of first dose of study treatment to the date of first documented disease progression (per RECIST v1.1) or death due to any cause

Proportion of patients with best overall response of CR, PR, or SD

Time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Glioma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Pancreatic Cancer

Neuroepithelioma

Binimetinib 45mg is orally administered twice daily.

Binimetinib 15 MG

Chigusa Morizane, M.D., Ph.D.

Tomoyuki Satake, M.D., Ph.D.

Tomoyuki Satake, M.D.

Ichiro Kinoshita, M.D., Ph.D.

Masafumi Kanai, M.D., Ph.D.

Keigo Komine, M.D., Ph.D.

Kenji Tsuchihashi, M.D., Ph.D.

This study is an open-label, parallel, 2-cohort, multicenter, investigator-initiated Phase 2 trial to evaluate the efficacy and safety of binimetinib in patients with advanced or recurrent low-grade glioma or pancreatic cancer harboring BRAF fusion/rearrangement.

This study is an open-label, parallel, 2-cohort, multicenter, investigator-initiated Phase 2 trial. Eligible patients are with recurrent low-grade glioma (grade 1 and grade 2 tumors according to WHO classification) or advanced or recurrent pancreatic cancer harboring BRAF fusion/rearrangement. Patients receive binimetinib 45mg administered orally, twice daily.

Analyses will be performed on each of the two cohorts:

Cohort A: low-grade glioma Cohort B: pancreatic cancer

Binimetinib in Patients With BRAF Fusion-positive Low-grade Glioma or Pancreatic Cancer (Perfume)

Phase II Investigator-initiated Trial of Binimetinib in Patients With BRAF Fusion-positive Low-grade Glioma or Pancreatic Cancer (Perfume)

Overall response rate (ORR) defined as the combined incidence of complete response (CR) and PR, within cohort A FAS, cohort B FAS, and confirmed no less than 4 weeks after the criteria for response are first met, based on RECIST v1.1. ORR will be confirmed by independent blinded central review assessment.

Overall response rate (ORR) defined as the combined incidence of complete response (CR) and PR, within cohort A FAS, cohort B FAS, and confirmed no less than 4 weeks after the criteria for response are first met, based on RECIST v1.1. ORR will be performed by investigator assessment.

Overall response rate (ORR) defined as the combined incidence of complete response (CR) and PR, within cohort A FAS, and confirmed no less than 4 weeks after the criteria for response are first met, based on Response Assessment in Neuro-Oncology (RANO) criteria. ORR will be confirmed by local site investigator assessment.

Overall response rate (ORR) defined as the combined incidence of complete response (CR) PR and SD, within cohort A FAS, and confirmed no less than 4 weeks after the criteria for response are first met, based on Response Assessment in Neuro-Oncology (RANO) criteria. ORR will be confirmed by local site investigator assessment.

Progression-free survival (PFS) defined as the time from the date of enrollment to the date of the first documentation of objective progression of disease (PD), clinically diagnosed symptomatic deterioration, or death due to any cause in the absence of documented PD, whichever occurs first within cohort A FAS and cohort B FAS.

Overall survival (OS) defined as the time from date of enrollment to date of death due to any cause within cohort A FAS and cohort B FAS.

Disease control rate (DCR) defined as the percentage of patients with a confirmed complete response (CR), partial response (PR) or stable disease (SD) as the best overall according to RECIST version 1.1 within cohort A FAS and cohort B FAS.

Duration of Response (DOR) defined as the time from the date of first documentation of CR or PR to the date of first documentation of disease progression or date of death from any cause, whichever occurs first within cohort A FAS and cohort B FAS.

Defined as the percentage of patients who experienced each adverse event. The severity of AEs were evaluated by the investigator according to Japan Clinical Oncology Group (JCOG) Japanese translation of the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0-JCOG) within cohort A FAS and cohort B FAS.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC	NCT03333343	EGFR-mutant Non...	EGF816 trametinib ribociclib LXH254 INC280 gefitinib	18 Years -	Novartis
Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC	NCT03333343	EGFR-mutant Non...	EGF816 trametinib ribociclib LXH254 INC280 gefitinib	18 Years -	Novartis
Binimetinib in Patients With BRAF Fusion-positive Low-grade Glioma or Pancreatic Cancer (Perfume)	NCT06159478	Low-grade Gliom... Pancreatic Canc...	Binimetinib 15 ...	12 Years -	National Cancer Center, Japan

Spots Global Cancer Trial Database for braf rearrangement