Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Lymphoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Ensartinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Esteban Sanchez

Danielle Pancirer

Heather Wakelee, M.D.

Virginia Schmidt

Alden Chiu, M.D.

Lara Edens

Sally York, MD

Kristen Schumacher

Anne Traynor, M.D.

This is an open-label, multicenter, intermediate-sized expanded access treatment protocol to the existing IND 111,695 for ensartinib (X-396). The treatment plan is designed to provide ensartinib to participants with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC).

Open-label, multi-center, intermediate-sized expanded access treatment protocol for X396-CLI-101 (Phase I/II, First-in-Human, Dose-Escalation Study of X-396 in Patients with Advanced Solid Tumors and Expansion Phase in Patients with ALK+ Non-Small Cell Lung Cancer)

Expanded Access to Ensartinib for Participants With ALK+ NSCLC

Expanded Access Intermediate-Size Patient Population Protocol

Xcovery Holdings, Inc.

Nicolas Girard, MD, PhD

The study will evaluate progression-free survival, overall survival, best response and duration of treatment in patients with advanced ALK- and ROS1-positive non-small cell lung cancer who received lorlatinib as part of the French expanded access program.

IFCT-1803 LORLATU study will evaluate progression-free survival, overall survival, best response and duration of treatment in patients with advanced ALK- and ROS1-positive non-small cell lung cancer who received lorlatinib (PF-06463922) as part of the French expanded access program. Those outcomes will be correlated to clinical, pathological, and radiological characteristics of patients.

Efficacy of Treatment Sequences in Patients With Non-small Cell Lung Cancer Receiving Lorlatinib

Efficacy of Treatment Sequences in Patients With ALK and ROS-1 Positive Non-small Cell Lung Cancer Who Received Lorlatinib as Part of the French Expanded Access Program

time from first dose of treatment to first occurrence of disease progression or death from any cause during the study

best response recorded from the start of treatment until disease progression or start of further anti-cancer treatment

time from first dose of treatment to discontinuation of treatment or death from any cause during the study

site of disease progression after each line of treatment

this may be disease progression, toxicity, death, other

time between first occurrence of disease progression and discontinuation the treatment

in patients with CNS measurable lesion, best response on CNS locations recorded from the start of treatment until disease progression or start of further anti-cancer treatment

time from first dose of treatment to first occurrence of disease progression in the CNS or death from any cause during the study

is defined as the time from the first dose of treatment dose and death from any cause

complications of lorlatinib therapy will be recorded

Pfizer

Intergroupe Francophone de Cancerologie Thoracique

Micronutrients

Hematinics

Amino Acids

Vitamins

Pembrolizumab

Carboplatin

Lenvatinib

Pemetrexed

Tyrosine Kinase Inhibitors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tyrosine

Folinic Acid

Folate

Vitamin B9

Dr Joanne Chiu, MBBS

Dr James Ho, MBBS

Adding chemotherapy or anti-VEGF to immunotherapy is an emerging strategy to enhance the efficacy of immunotherapy in many cancers. This phase 2 study aims to explore the preliminary efficacy of combination pembrolizumab with lenvatinib and chemotherapy in NSCLC patients with sensitizing EGFR, ALK, or ROS1 genetic aberration refractory to standard targeted therapy.

Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC

A Phase 2 Open-label Single-arm Study to Evaluate the Combination of Pembrolizumab, Lenvatinib and Chemotherapy in Non-small Cell Lung Cancer (NSCLC) Harbouring Targetable Mutation and Failed Standard Tyrosine Kinase Inhibitors

Proportion of patients who have a confirmed CR or PR per RECIST 1.1

Time from randomization to the first documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first

Time from randomization to death from any cause or last follow-up date

Dr Joanne CHIU

Assistant Professor

Bevacizumab

Cisplatin

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

4 cycles of induction every 3 weeks with :

* Carboplatin area under curve 6 mg/mL per minute per IV route or Cisplatin 75 mg/m² per IV route
* Pemetrexed 500 mg/m² per IV route
* Atezolizumab 1200 mg per IV route
* Bevacizumab 15 mg/kg per IV route For patients without disease progression, treatment will be followed by maintenance therapy by Atezolizumab + Pemetrexed and Bevacizumab administered at the same dosage on 3-week cycles

4 cycles of induction every 3 weeks with :

* Carboplatin area under curve 6 mg/mL per minute per IV route or Cisplatin 75 mg/m² per IV route
* Pemetrexed 500 mg/m² per IV route
* Atezolizumab 1200 mg per IV route For patients without disease progression, treatment will be followed by maintenance therapy by Atezolizumab + Pemetrexed administered at the same dosage on 3-week cycles

4 cycles of induction every 3 weeks of cisplatine,pemetrexed, atezolizumab + bevacizumab and patients without disease progression, treatment will be followed by maintenance therapy by Atezolizumab + Pemetrexed +/- Bevacizumab administered at the same dosage on 3-week cycles

Carboplatin + Pemetrexed + Atezolizumab + Bevacizumab

Carboplatin + Pemetrexed + Atezolizumab

BYLICKI Olivier, MD

GRELLARD Jean-Michel, Project manager

JUSTEAU Gregoire, MD

HOMINAL Stéphane, MD

DESCOURT Renaud, MD

Sebastien COURAUD, PhD

GERVAIS Radj, MD

GRELLARD Jean-Michel

JANICOT Henri, MD

MONNET Isabelle, MD

MORO-SIBILOT Denis, PhD

Acya BIZIEUX, MD

Diane MOREAU, MD

Eric HUCHOT, MD

Alexis CORTOT, MD

VERGNENEGRE Alain, PhD

PEROL Maurice, MD

GREILLER Laurent, PhD

Hugues MOREL, MD

DOUBRE Helene, MD

DANIEL Catherine, MD

VEILLON Rémi, MD

COURAUD Sébastien, MD

LENA Hervé, MD

BOTA Suzanna, MD

FOURNEL Pierre, PhD

SCHOTT Roland, MD

PALEIRON Nicolas, MD

BIGAY GAME Laurence, MD

Gonzague DE CHABOT, MD

ARPIN Dominique, MD

PELONI Jean-Michel, MD

The objective of this study is to assess the efficacy of the combination of Platinum (carboplatin or cisplatin), Pemetrexed, Atezolizumab+/- Bevacizumab if eligible, in stage IIIB/IV non-squamous non-small cell lung cancer patients with progression-enhancing mutations following targeted therapies.

In patients with an EGFR mutation, several phase III studies comparing EGFR tyrosine kinase inhibitors (TKIs) with chemotherapy have shown a benefit of TKI over chemotherapy, with no demonstrated benefit on overall survival. After a first line of treatment with a TKI, most patients progress and are eligible according to the mechanism of progression to a TKI of 3rd generation in case of T790M resistance or chemotherapy. In patients with ALK translocation, crizotinib has been shown to be beneficial in first line compared to a platinum doublet.Despite these major advances, most patients are progressing after targeted treatments and chemotherapy and are facing the problem of anti-PD1 / PDL1 treatment.

Open-label, multicentre, non-randomized two parallel cohorts phase II study

A Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/-Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies

A Multicentre Phase II, Open-label, Non-randomized Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/- Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies

GFPC

Centre Francois Baclesse

All patients included in Explore ALK GFPC 03-2019 study who agree to participate in Bioexalk.

1. Tissue : RNAseq will be performed on tumor biopsy (10 slides of 5 microns) to identify the ALK fusion partner and its variant and associated co-mutations.
2. ctDNA : NGS panel on DNA including a large panel of fusions and mutations will be performed on blood samples

RNAseq

Florian GUISIER

Aurélie SWALDUZ

Diane MOREAU

Géraldine FRANCOIS

Julian PINSOLLE

Lise THIBONNIER

Marie MARCQ

Cécile DUJON

Olivier MOLINIER

Eric DANSIN

Alexis CORTOT

Pierre BOMBARON

Karima SABOUNDJI

Anne MADROSZYK

Camille TRAVERT

Karim AMRANE

Hugues H MOREL

Catherine DANIEL

Aldo RENAULT

Gwenaelle LE GARFF

Hélène DOUBRE

Jean-Michel PELONI

Clarisse AUDIGIER VALETTE

Olivier BYLICKI

Gonzague DE CHABOT

Benjamin BESSE

Alexa MAIROVITZ

Nicolas DELBERGHE

Christos CHOUAID

BioEXALK is a prospective study evaluating the biological characteristics of advanced ALK-rearranged NSCLC treated with next generation TKIs in first line, included in the national EXPLORE ALK cohort (GFPC 03-2019), a non-interventional, national, multi-center cohort of ALK-rearranged NSCLC patients.

BioExALK study will be proposed to every patient included in the Explore ALK GFPC 03-2019 study.

Biological analysis will be performed on tumor tissue at diagnosis and at the time of disease progression when available and on circulating tumor DNA (ctDNA).

For plasma testing, after obtained patient consent, blood samples will be taken and analyzed at the Léon Bérard Center (Lyon).

Biological analysis on tissue obtained at diagnosis and at disease progression will be collected and be sent for centralized analysis to the Rouen University Hospital.

BioEXALK is a prospective study evaluating the biological characteristics of advanced ALK-rearranged NSCLC treated with new generation TKIs in first line, included in the national EXPLORE ALK cohort (GFPC 03-2019).

Explore ALK GFPC 03-2019 is a non-interventional, national, multi-center cohort of ALK-rearranged NSCLC patients, whose RCB reference is 2020-A00771-38 and which obtained an approval from the IDF II Ethic Committee on 25/05/2020. Biological analysis will be performed on tissue at diagnosis and at the time of disease progression when available and on circulating tumor DNA (ctDNA) on three timepoints (diagnosis, at first tumor evaluation and at the time of disease progression).

* Tissue : RNAseq will be performed on tumor biopsy (10 slides of 5 microns) to identify the ALK fusion partner and its variant and associated co-mutations..
* ctDNA : NGS panel on DNA including a large panel of fusions and mutations will be performed on blood samples (30mL on EDTA or STRECKs tubes) at diagnosis, at the time of the first evaluation and at the time of progression).

For plasma testing, after obtained patient consent, blood samples (35mL on EDTA or STRECKs tubes) at diagnosis, at the first evaluation and at disease progression will be taken.

The ALKis include alectinib and brigatinib as first-line therapy or other drugs with marketing authorizations (lorlatinib, entrectinib) or in early access programs (EAPs).

Liquid biopsies will be analyzed with a NGS panel allowing the identification of ALK fusion partners and resistance mechanisms (mutations, fusions, copy number variations). Samples will be sent for centralized analysis to the Léon Bérard Center (Lyon).

For biological analysis on tissue obtained at diagnosis, the ALK fusion partner and its variant will be identified by RNAseq. Whenever a tissue re-biopsy is performed at the time of disease progression as part of the standard of care management of the patient, the remaining tissue sample will be collected as part of the BioExALK study, so that RNAseq analysis will be performed to look for resistance mechanisms. Tissue samples (10 slides of 5 microns) will be sent for centralized analysis to the Rouen University Hospital.

Analysis of Biological Characteristics of Advanced ALK-rearranged NSCLC

Biological Characterization of Advanced ALK-rearranged Non-small Cell Lung (NSCLC) Cancer Included in EXPLOREALK Study

PFS assessed by local review using RECIST v1.1, defined as time from treatment initiation to the first clinical or radiological progression or death from any cause

OS defined as time from treatment initiation to death from any cause.

DoR assessed by local review using RECIST v1.1, defined as time from treatment initiation to the first clinical or radiological progression, death, consent withdrawn, adverse event, protocol deviations, lost to follow-up, or initiation of a new line of anticancer therapy.

ORR defined as objective response rate of complete response or partial response measured by local review RECIST v1.1.

ctDNA clearance will be determine as clearance of the fusion when detectable and/or clearance of relevant mutations when fusion not detected

The following mechanisms of resistance will be assessed: secondary mutations on ALK, mutations or translocations on other genes of interest, histological transformations

ALK fusion partner and co-mutation identifications based on liquid and tissue biopsies at Baseline

Takeda

Groupe Francais De Pneumo-Cancerologie

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Expanded Access to Ensartinib for Participants With ALK+ NSCLC	NCT04146571	Non-Small Cell ... ALK Gene Rearra...	Ensartinib	18 Years -	Xcovery Holdings, Inc.
Efficacy of Treatment Sequences in Patients With Non-small Cell Lung Cancer Receiving Lorlatinib	NCT03727477	Non-small Cell ... ALK Gene Rearra... ROS-1 Gene Rear...		18 Years -	Intergroupe Francophone de Cancerologie Thoracique
Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC	NCT04989322	Nsclc EGFR Activating... EGF-R Positive ... ALK Gene Rearra... ROS1 Gene Rearr... ROS1 Positive N...	Pembrolizumab Lenvatinib Pemetrexed Carboplatin	18 Years -	The University of Hong Kong
Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC	NCT04989322	Nsclc EGFR Activating... EGF-R Positive ... ALK Gene Rearra... ROS1 Gene Rearr... ROS1 Positive N...	Pembrolizumab Lenvatinib Pemetrexed Carboplatin	18 Years -	The University of Hong Kong
A Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/-Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies	NCT04042558	NSCLC Stage III... NSCLC Stage IV EGFR Gene Mutat... ALK Gene Rearra... ROS1 Gene Mutat...	Carboplatin + P... Carboplatin + P...	18 Years - 75 Years	Centre Francois Baclesse
Analysis of Biological Characteristics of Advanced ALK-rearranged NSCLC	NCT05122806	Non-small Cell ... ALK Gene Rearra...	RNAseq	18 Years -	Groupe Francais De Pneumo-Cancerologie
Analysis of Biological Characteristics of Advanced ALK-rearranged NSCLC	NCT05122806	Non-small Cell ... ALK Gene Rearra...	RNAseq	18 Years -	Groupe Francais De Pneumo-Cancerologie
A Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/-Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies	NCT04042558	NSCLC Stage III... NSCLC Stage IV EGFR Gene Mutat... ALK Gene Rearra... ROS1 Gene Mutat...	Carboplatin + P... Carboplatin + P...	18 Years - 75 Years	Centre Francois Baclesse

Spots Global Cancer Trial Database for alk gene rearrangement positive