Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Carcinoma

Lung Neoplasms

Adenocarcinoma

Adenocarcinoma of Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Crizotinib

Ceritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants on this arm took oral LDK378 750 mg once daily.

LDK378/Ceritinib was supplied as 150 mg hard gelatin capsules and administered orally

LDK378

Novartis Pharmaceuticals

A single-arm, open-label, two-stage multicenter, phase II study. Patients were pre-screened for ALK positive status. Treatment with LDK378 at 750 mg qd was continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anticancer therapy and/or died. LDK378 was continued beyond RECIST defined progressive disease (PD) as assessed by the investigator, if in the judgment of the investigator, there was evidence of clinical benefit. Patients who discontinued the study medication in the absence of progression continued to be followed for tumor assessment until the time of PD as assessed by the investigator. Male and female patients aged 18 or over with ALK-rearranged non-small cell cancer (NSCLC) were screened for eligibility. Patients had to have received no prior crizotinib, and had to be chemotherapy-naïve or been pretreated with cytotoxic chemotherapy (up to three prior lines).

LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by the investigator. CR:Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by BIRC. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by investigator assessment per RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by BIRC assessment per RECIST 1.1. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

DCR per RECIST 1.1 is the percentage of participants with best overall response of CR, PR, stable disease (SD) or Non-CR/Non-PD. CR: Disappearance of all non-nodal target lesions. Also, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions that would qualify for PD. PD: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm.

TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator. This was only on participants with confirmed CR or PR. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by BIRC assessment. This was only on participants with confirmed CR or PR. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by investigator.

OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by BIRC.

PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by investigator and BIRC assessments.

OS, defined as time from first dose of LDK378 to death due to any cause

LDK378 Ceritinib)

LDK378 (Ceritinib)

Age, Continuous

Sex: Female, Male

Asian

Caucasian

Black

Other

Race/Ethnicity, Customized

The Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug.

Study Director

Overall Response Rate (ORR) by Investigator Assessment

ORR by Blinded Independent Review Committee (BIRC)

The set consisted of patients in the Full Analysis Set (FAS) who had confirmed complete response (CR) or partial response (PR) by investigator.

Duration of Response (DOR) as Per Investigator

The set consisted of patients in the Full Analysis Set (FAS) who had confirmed complete response (CR) or partial response (PR) as assessed by BIRC.

Duration of Response (DOR) as Per BIRC

DCR per Investigator

DCR per BIRC

Disease Control Rate (DCR) as Per Investigator and BIRC

Time to Response (TTR) as Per Investigator

Time to Response (TTR) as Per BIRC

The set consisted of patients in the Full Analysis Set (FAS) who had measurable target lesions in brain at baseline by investigator.

Overall Intracranial Response Rate (OIRR) as Per Investigator

The set consisted of patients in the Full Analysis Set (FAS) who had measurable target lesions in brain at baseline by BIRC.

Overall Intracranial Response Rate (OIRR) as Per BIRC

PFS per Investigator

PFS per BIRC

Progression-free Survival (PFS) Per Investigator and BIRC

Overall Survival (OS)

Overall Study

Small Cell Lung Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Small Cell Lung Cancer

Trametinib

Dabrafenib

Trametininb

MAP requests are initiated by a licensed physician. https:// www.novart is.com/healthcare-professionals/managed-access-programs

The purpose of this Managed Access Program (MAP) Cohort Treatment Plan is to provide guidance to the Physician for the treatment and monitoring of eligible patients diagnosed with BRAF V600E/K activating mutation-positive advanced NSCLC using trametinib/dabrafenib in the Cohort MAP CTMT212X2002I.

The Physician should follow the suggested treatment guidelines. Furthermore, the Physician must comply with the MAP Agreement Letter and applicable local laws and regulations.

Prior to inclusion of a patient in the Cohort, the requesting Physician must submit a request for access to the product in GEMS (Grants, External Requests and Managed Access System) accessible through https://www.novartis.com/our-focus/healthcare-professionals/managedaccess-programs providing the rationale for the request and relevant medical history of the patient.

The request is then assessed against the MAP and Cohort inclusion/exclusion criteria by the medical team experienced with the product and indication. Upon the required approvals, the patient is included in the Cohort.

Managed Access Program Cohort Treatment Plan CTMT212X2002I to Provide Access to Trametinib and Dabrafenib Combination Therapy for Patients With BRAF V600 Mutation-positive Advanced Non-Small Cell Lung Cancer

Managed Access Program (MAP) Cohort Treatment Plan CTMT212X2002I to Provide Access to Trametinib and Dabrafenib Combination Therapy for Patients With BRAF V600 Mutation-positive Advanced Non-Small Cell Lung Cancer (NSCLC).

Pharmaceutical Solutions

Micronutrients

Hematinics

Vitamins

Pemetrexed

Docetaxel

Tubulin Modulators

Antimitotic Agents

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Patients in this arm received 750 mg of ceritinib.

Patients in this arm received chemotherapy of either pemetrexed or docetaxel as determined by BIRC.

Ceritinib is the investigational treatment and is referred to as the investigational study drug and was provided as 150 mg hard gelatin capsules for oral use. The dose was 750 mg once daily.

Pemetrexed was one of the chemotherapy treatments. Pemetrexed, a reconstituted solution, was intravenously administered over 10 minutes at 500 mg/m2 every 21 days.

pemetrexed

Docetaxel was one of the chemotherapy treatments. Docetaxel, a reconstituted solution, was intravenously administered over 1 hour, at 75 mg/m2 every 21 days.

docetaxel

The primary purpose of the study was to compare the antitumor activity of LDK378 vs. chemotherapy in patients previously treated with chemotherapy (platinum doublet) and crizotinib. Patients in the chemotherapy arm were given the option to switch to LDK378 after confirmed progressive disease (PD), while also had the choice to continue with pemetrexed treatment.

LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib

A Phase III, Multicenter, Randomized, Open-label Study of Oral LDK378 Versus Standard Chemotherapy in Adult Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer Who Have Been Treated Previously With Chemotherapy (Platinum Doublet) and Crizotinib

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.

OS is defined as time from date of randomization to date of death due to any cause.

ORR is defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR)

DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to underlying cancer

DCR is defined as the proportion of patients with best overall response of CR, PR, or stable disease (SD)

TTR is defined as the time from date of randomization to date of first documented response (CR or PR)

OIRR is defined as the ORR based on lesions in brain (target, nontarget lesions (and new lesions, if applicable) and calculated as the proportion of patients with a best overall confirmed response of CR or PR in the brain per modified RECIST 1.1\* as assessed by BIRC neuroradiologist.

IDCR is defined as the DCR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated as the proportion of patients with a best overall response of CR or PR or SD (or non-CR/nonPD) in the brain per modified RECIST 1.1\* as assessed by BIRC neuro-radiologist.

DOIR is defined as the DOR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated from the time of first documented response of CR or PR to the date of the first documented disease progression in the brain or death due to any cause per modified RECIST 1.1\* as assessed by BIRC neuro-radiologist.

Chemotherapy

Total

The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned by randomization.

Although 116 patients were randomized to the Chemotherapy arm, 3 did not receive study drug and were excluded form the Safety set.

Progression Free Survival (PFS) Blinded Independent Review Committee Per Blinded Independent Review Committee (BIRC)

Overall Response Rate (ORR)

Duration of Response (DOR)

Disease Control Rate (DCR)

Time to Response (TTR)

Patient Reported Outcomes (PRO)

Time to Definitive Deterioration

Overall Intracranial Response Rate (OIRR)

Intracranial Disease Control Rate (IDCR)

Duration of Intracranial Response (DOIR)

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Naporafenib

LXH254 will be supplied as tablet for oral use.

LXH254

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

LTT462

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

Carboplatin

Cisplatin

Ceritinib patients were on continuous oral dosing of ceritinib 750 mg once daily in fasted state.

Chemotherapy patients (Induction per Investigator's choice) were on four 21-day cycles of Pemetrexed 500mg/m2 iv + Cisplatin 75 mg/m2 or Pemetrexed 500 mg/m2 iv + Carboplatin AUC 5-6 iv followed by Pemetrexed 500 mg/m2 every 21 days followed by Pemetrexed maintenance in non-progressors, etc (other usual rule to stop treatment).

Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule. Ceritinib (LDK378) was the investigational treatment and is referred to as the investigational study treatment/drug.

Pemetrexed was administered at a dose of 500 mg/m2 as an iv infusion on Day 1 of each 21-day cycle to patients randomized to the chemotherapy arm.

Cisplatin was administered by IV at a dose of 75 mg/m2 every 21 days for up to 4 cycles.

Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles

The primary purpose of the study was to compare the antitumor activity of LDK378 versus reference chemotherapy. Patients in the chemotherapy arm were given the option to switch to LDK378 after confirmed progressive disease (PD), while also had the choice to continue with pemetrexed treatment.

LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

A Phase III Multicenter, Randomized Study of Oral LDK378 Versus Standard Chemotherapy in Previously Untreated Adult Patients With ALK Rearranged (ALK-positive), Stage IIIB or IV, Non-squamous Non-small Cell Lung Cancer

PFS defined as time from date of randomization to date of first documented disease (as assessed by Blinded Independent Review Committee (BIRC) per RECIST 1.1) or date of death due to any cause

OS defined as time from date of randomization to date of death due to any cause

ORR defined as the proportion of patients with a best overall response defined as Complete Response (CR) or Partial Response (PR) as evaluated by Blinded Independent Review Committee (BIRC) and by investigator assessment per RECIST 1.1

DOR defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause

DCR defined as the proportion of patients with best overall response of CR, PR, or Stable Disease (SD)

TTR defined as the time from date of randomization to date of first documented response (CR or PR)

The time to definitive deterioration from the date of randomization to the date of event for disease related symptoms.

Chemotherapy patients (Induction per Investigator's choice)

The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned by randomization. According to the intent to treat principle, patients were analyzed according to the treatment and strata to which they had been assigned during the randomization procedure.

Among the 187 patients randomized to chemotherapy arm, 12 patients were not treated.

Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC)

Patient Reported Outcomes

Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm.

AUY922 was to be administered weekly.

Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm.

Pemetrexed or docetaxel was to be was to be given once every three weeks.

AUY922 was to be given by i.v. once weekly at 70 mg/m2 until disease progression, death or any other reason for discontinuation from study treatment.

AUY922

Docetaxel was to be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity

Pemetrexed was to be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity

The purpose of this study was to determine if AUY922 had superior efficacy when compared to chemotherapy agents docetaxel or pemetrexed in patients whose tumor had EGFR mutations.

The primary purpose of this study was to compare the efficacy of AUY922, when administered i.v. on a once-weekly schedule at 70 mg/m2, versus docetaxel or pemetrexed in adult patients with advanced NSCLC, whose tumors harbored EGFR activating mutations, and had developed resistance to EGFR TKI.

An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations

A Multicenter, Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations Who Have Progressed on Prior EGFR TKI Treatment

Compared PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. Progression-free survival (PFS) based on local investigator assessment per RECIST 1.1 was the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

ORR was to be compared between treatment arms. The ORR was to be based on local investigator assessment per Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). Per this criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.This outcome measure was originally planned to be analyzed up to 24 months. The DMC recommendation at the IA was to stop the study for futility. As a result, collection of all the efficacy assessments was stopped at that time.

OS is defined as the time from the date of randomization to date of death due to any cause. If a death has not been observed by the date of analysis cutoff, then OS was to be censored at the last known date patient was alive.

Duration of DCR will be compared between treatment arms. The duration of DCR will be based on local investigator assessment per RECIST 1.1

TTR was to compare between treatment arms. The TTR was to be based on local investigator assessment per RECIST 1.1

The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1

To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.

Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer	NCT01685138	Non-Small Cell ...	LDK378	18 Years -	Novartis
Managed Access Program Cohort Treatment Plan CTMT212X2002I to Provide Access to Trametinib and Dabrafenib Combination Therapy for Patients With BRAF V600 Mutation-positive Advanced Non-Small Cell Lung Cancer	NCT04507919	Small Cell Lung...	Dabrafenib Trametininb	18 Years - 99 Years	Novartis
LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib	NCT01828112	Non-Small Cell ...	Ceritinib pemetrexed docetaxel	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
LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer	NCT01828099	Non-Small Cell ...	Ceritinib Pemetrexed Cisplatin Carboplatin	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
LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer	NCT01685138	Non-Small Cell ...	LDK378	18 Years -	Novartis
LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer	NCT01685138	Non-Small Cell ...	LDK378	18 Years -	Novartis
An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations	NCT01646125	Advanced Non Sm...	AUY922 Docetaxel Pemetrexed	18 Years -	Novartis
An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations	NCT01646125	Advanced Non Sm...	AUY922 Docetaxel Pemetrexed	18 Years -	Novartis

Spots Global Cancer Trial Database for treatment of lung cancer after first metastasis