Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Irinotecan

Taxane

Tubulin Modulators

Antimitotic Agents

Topoisomerase I Inhibitors

Enzyme Inhibitors

approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the LJM716-BYL719 combination arm to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan).

approximately 42 previously treated esophageal squamous cell carcinoma (ESCC) patients will be enrolled to the Paclitaxel, Docetaxel or Irinotecan arm (physician's choice arm) to evaluate the anti-tumor activity and further assess the safety, tolerability and anti-tumor activity of the LJM716-BYL719 combination versus current therapies (physician's choice of paclitaxel, docetaxel or irinotecan).

LJM716 (10-40 mg/kg) will be given as a once weekly infusion beginning on cycle 1 day 1. The doses of LJM716 will be increased as dose escalation proceeds until a maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) is established.

LJM716

BYL719 (200-400 mg) will be administered orally on a once daily schedule starting cycle 1 day 1. The doses of BYL719 will be increased as dose escalation proceeds until a maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) is established.

BYL719

In the Phase II portion of the study Paclitaxel is one of the 3 physician's choice drug which allows single-agent paclitaxel to be used per manufacturer's label.

In the Phase II portion of the study Docetaxel is one of the 3 physician's choice drug which allows single-agent docetaxel to be used per manufacturer's label.

In the Phase II portion of the study Irinotecan is one of the 3 physician's choice drug which allows single-agent irinotecan to be used per manufacturer's label

Novartis Pharmaceuticals

To study the safety and efficacy of the combination of LJM716 and BYL719 against currently available treatments of physician's choice in previously treated esophageal squamous cell carcinoma patients.

The study design included a Phase 1b dose escalation portion to define the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) for the combination of LJM716 and alpelisib, followed by an open-label, randomized Phase 2 part to compare anti-tumor activity of LJM716-alpelisib combination versus physician's choice of second-line therapy (paclitaxel, docetaxel, irinotecan). However, the phase 2 part was not conducted as the study was terminated early due to limited anti-tumor activity with LJM716-alpelisib combination observed in phase 1b.

Study of Safety & Efficacy of the Combination of LJM716 & BYL719 in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)

A Phase Ib/II, Open-label Study of LJM716 in Combination With BYL719 Compared to Taxane or Irinotecan in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)

The open-label dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or Recommended Phase II Dose (s) guided by the safety (incidence of dose limiting toxicities), efficacy, pharmacokinetics and pharmacodynamics data.

Progression-free survival is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate assessment.

This will be assessed by looking at the number of Adverse Events (AEs), serious AEs (SAEs) changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity.

BOR will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

Plasma concentration versus time profiles Plasma PK parameters will be used to characterize the PK profiles of LJM716 and BYL719 when used in combination

Overall response rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

Duration of response will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

Disease control rate will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

Overall survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

Progression free survival will be used to further assess the anti-tumor activity of LJM716-BYL719 combination versus Paclitaxel, Docetaxel or Irinotecan.

Symptoms and General Pathology

Recurrence

Squamous Cell Carcinoma of Head and Neck

Antibodies

Cetuximab

Immunoglobulins

Antineoplastic Agents, Immunological

cetuximab

To establish whether LJM716 in combination with cetuximab is safe and has beneficial effects in patients with platinum-pretreated recurrent/metastatic head and neck squamous cell carcinoma.

Study of Efficacy and Safety of LJM716 and Cetuximab in Head and Neck Squamous Cell Carcinoma Patients

A Phase Ib/II, Multicenter Study of LJM716 in Combination With Cetuximab in Patients With Platinum-pretreated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Assessment of the preliminary anti-tumor activity of LJM716 in combination. Change in target lesion measurements, from baseline as per RECIST 1.1

The dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose of LJM716 in combination with cetuximab

Patients with an Objective Overall Response (OOR) were those whose best response to treatment was a complete response (CR) or a partial response (PR) assessed by imaging, as pr RECIST 1.1.

blood concentration versus time profiles blood PK parameters will be used to characterize the PK profiles of LJM716 and cetuximab concentration when used in combination

BOR will be used to further assess the anti-tumor activity of LJM716-cetuximab combination.

Duration of response will be used to further assess the anti-tumor activity of LJM716-cetuximab combination

Overall survival will be used to further assess the anti-tumor activity of LJM716-cetuximab combination

Progression free survival will be used to further assess the anti-tumor activity of LJM716-cetuximab combination

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Trastuzumab

A treatment cycle will consist of 28 days. Treatment doses for trastuzumab and LJM716 will be fixed at trastuzumab 2mg/kg weekly, and LJM716 20mg/kg weekly. The exception to this is if dose de-escalation results in treatment of patients at dose level 1, where LJM will be dosed at 10mg/kg weekly. On Arm A, BYL719 was administered orally once daily continuously at one of 5 dosing levels, beginning with dose level 3, 250mg orally daily. On Arm B, BYL719 will be administered orally once daily during 4 of 7 days in a week, at one of 5 dosing levels, beginning with dose level 3, 250mg orally daily. This means BYL719 will be given to patients on Arm B during days 1-4, 8-11, 15-18, and 22-25 of each cycle. The dose-finding phase will follow a Continuous Reassessment Methods (CRM) phase I biostatistical design.

TRASTUZUMAB

Shanu Modi, MD

This is a Phase I study. The purpose of this study is to determine what is the best dose of the study drug BYL719 in combination with the study drug LJM716 and traztuzumab (Herceptin®). The study will test the safety of the combination of these three drugs, and to find out the effects, good and/or bad, that these three drugs have on the patient and breast cancer.

Open-Label Study Evaluating the Safety and Tolerability of LJM716, BYL719 and Trastuzumab in Patients With Metastatic HER2+ Breast Cancer

A Phase I, Open-Label Study Evaluating the Safety and Tolerability of LJM716, BYL719 and Trastuzumab in Patients With Metastatic HER2+ Breast Cancer

The MTD is defined as per the Continual Reassessment Method. The RDE will be determined by the Principal Investigator with input from other investigators and Novartis, and will be based on the MTD, review of required intra-patient dose de-escalations, pharmacodynamic evaluations, and consideration of toxicities occurring in cycles 2+.

Novartis

Memorial Sloan Kettering Cancer Center

Stomach Neoplasms

Stomach Diseases

Stomach Cancer

This is a multicenter, open-label, dose escalation, phase I study to estimate the Maximum Tolerated Dose (MTD) or a lower Recommended Dose for Expansion (RDE) of LJM716 in combination with trastuzumab in patients with Human Epidermal growth factor Receptor 2 (HER2) overexpressing Metastatic Breast Cancer (MBC) or gastric cancer (MGC). The study consists of a dose escalation part and a dose expansion part. LJM716 will be administered intravenously once weekly unless a less frequent dosing regimen such as every 2 weeks or once every 4 weeks is introduced. Patients will continue on their trastuzumab dosing, administered intravenously once weekly at 2mg/kg. During dose escalation, a minimum of 15 patients are anticipated to be treated in successive cohorts. The dose escalation will continue until the MTD/RDE is declared. The RDE dose selected will either be the MTD or a dose below the MTD based on safety and Pharmacokinetic/Pharmacodynamic (PK/PD) considerations. Following the MTD/RDE declaration, approximately 20 MBC and 20 MGC patients will be enrolled in separate arms in the dose expansion part and treated at the MTD/RDE to further assess the safety, tolerability, and anti-tumor activity of the combination.

Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer

A Multicenter, Open-label, Dose Escalation, Phase I Study of LJM716 Administered Intravenously in Combination With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast Cancer or Gastric Cancer

Incidence of dose-limiting toxicities (DLTs)

Post-treatment change from baseline in pHER3 levels in the tumor

This primary purpose of this study is to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) and preferred dosing schedule of LJM716 given by IV infusion in adult patients with squamous cell carcinoma of head and neck, or esophagus, or HER2 overexpressing metastatic breast cancer or gastric cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Safety & Efficacy of the Combination of LJM716 & BYL719 in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)	NCT01822613	Esophageal Squa...	LJM716 BYL719 Paclitaxel Docetaxel Irinotecan	18 Years -	Novartis
Study of Efficacy and Safety of LJM716 and Cetuximab in Head and Neck Squamous Cell Carcinoma Patients	NCT02143622	Head and Neck S...	LJM716 cetuximab	18 Years -	Novartis
Open-Label Study Evaluating the Safety and Tolerability of LJM716, BYL719 and Trastuzumab in Patients With Metastatic HER2+ Breast Cancer	NCT02167854	Breast Cancer	BYL719 LJM716 TRASTUZUMAB	18 Years -	Memorial Sloan Kettering Cancer Center
Phase I Study LJM716 Combined With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast or Gastric Cancer	NCT01602406	Advanced HER2-p...	LJM716 Trastuzumab	18 Years -	Novartis
Study of Efficacy and Safety of LJM716 and Cetuximab in Head and Neck Squamous Cell Carcinoma Patients	NCT02143622	Head and Neck S...	LJM716 cetuximab	18 Years -	Novartis
A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer	NCT01598077	HER2 + Breast C... HER2 + Breast C... HER2 + Gastric ... Squamous Cell C... Esophageal Squa...	LJM716	18 Years -	Novartis
Study of Safety & Efficacy of the Combination of LJM716 & BYL719 in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)	NCT01822613	Esophageal Squa...	LJM716 BYL719 Paclitaxel Docetaxel Irinotecan	18 Years -	Novartis

Spots Global Cancer Trial Database for ljm716

Every month we try and update this database with for ljm716 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 ljm716

Every month we try and update this database with for ljm716 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 ljm716 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.