ALK Gene Mutation, ALK Sensitizing Mutation, NSCLC Stage IV
Conditions
Keywords
ALK mutation, NSCLC
Brief summary
The scope of GALILEO project (Genomic ALteratIons and cLonal EvOlution in ALK+ NSCLC) is to explore the feasibility of genomic longitudinal evaluation for ALK+ NSCLC patients in Italian routine practice and provide a detailed overview of resistance mechanisms and clinical outcomes according to current standard treatments.
Interventions
DIAGNOSTIC_TESTBiopsy (tissue or liquid)
At the time of diagnosis, all newly diagnosed ALK+ NSCLC patients eligible for first line treatment with alectinib or brigatinib or lorlatinib will be considered for the study. In case of progression, a multidisciplinary team (oncologists, interventional pneumologists and radiologists, surgeons) will discuss case-by-case the feasibility to procure an adequate biopsy from progressing lesions. Repeat biopsies will be performed within 2 weeks from multidisciplinary evaluation and before the start of subsequent treatment. If repeat biopsies are not technically or safely feasible or fail to yield sufficient material for genomic analysis, we will collect a whole blood drawn by venepuncture for the analysis of ctDNA.
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* a) histologically confirmed diagnosis of advanced NSCLC with ALK rearrangement detection by NGS (ALK+ NSCLCs patients detected at diagnosis by in hybridization (FISH), immunohistochememistry (IHC), or reverse transcriptase-PCR (RT-PCR) can be included if adequate tissue for NGS is available) b) to have received upfront treatment with alectinib, brigatinib or lorlatinib for at least 28 days c) ECOG PS 0-2 d) adult patients (aged ≥ 18 years) at the moment of diagnosis e) signing of informed consent approved by the local Ethic Committee
Exclusion criteria
a) Diagnosis of lung cancer without ALK rearrangement a) early withdrawn of treatment due to toxicity without evidence of radiological disease progression cannot be eligible for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with available NGS testing at diagnosis | 5 years | Percentage of ALK+ patients with adeguate tissue for NGS after diagnosisc biopsy |
| Percentage of patients with available NGS re-testing after progession (either tissue or ctDNA) to first-line treatment with II-III generation ALK-Inhibitor | 5 years | Percentage of patients who obtenied successfull NGS post-progression testing after re-biopsy or liquid biopsy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS to first-line treatment with II-III generation ALK-inhibitor | 5 years | Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years |
Other
| Measure | Time frame | Description |
|---|---|---|
| PFS to first-line treatment with II-III generation ALK-inhibitor | Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years | PFS to first-line, stratified according to ALK-rearrangement variants |
| PFS to lorlatinib according to secondary resistance mechanism | Time from treatment start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years | PFS to second-line lorlatinib, stratified according to type of resistance (SNV vs off-target) |
| OS to first-line treatment with II-III generation ALK-inhibitor | Time from treatment start until the date of death from any cause, assessed up to 5 years | OS to first-line, stratified according to ALK-rearrangement variants |
| Incidence of secondary resistance mutations (SNVs) after first line treatment | 5 years | Percentage of patients with SNV-based resistance diagnosed by tissue or liquid biopsy |
Countries
Italy
Contacts
Primary ContactEmanuele Vita, MD
Backup ContactEMILIO Bria, Prof.
Outcome results
None listed