Observational Retro-prospective Study on PD1/PDL1 Inhibitors Treatment Duration in Patients With NSCLC

Non-small Cell Lung Cancer Clinical Trial

— I-STOP  

Official title:

Observational Retro-prospective Study on Programmed Cell Death 1/ Programmed Cell Death Ligand1 (PD1/PDL1) Inhibitors Treatment Duration in Patients With Non Small Cell Lung Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05418660
• Other study ID #: I-STOP
• Status: Recruiting
• Start date: May 19, 2022
• Est. completion date: November 30, 2024

Study information

• Verified date: September 2023
• Source: University of Milano Bicocca
• Contact: Diego Cortinovis, MD
• Phone: 0392336040
• Email: diegoluigi.cortinovis[@]irccs-sangerardo.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Retrospective/ prospective, multicentre, international observational study on long-responders with non-small cell lung carcinoma patients treated with anti Programmed cell Death 1/ Programmed cell Death Ligand 1 (anti-PD1/PD-L1) in any line of treatment for at least 24 months with response partial/complete response or disease stability. Patients will be divided into two cohorts based on whether they stopped treatment at 24 months (not for toxicity) or continued by clinical choice and stratified according to treatment line and baseline PD-L1 expression.

Description:

Programmed cell Death protein / Ligand 1 (PD-1 / PD-L1) inhibitors Atezolizumab, Nivolumab and Pembrolizumab have demonstrated a great efficacy and a good safety profile in patients with Non-Small Cell Lung Cancer (NSCLC), both in first-line (PD-L1 expression > 50%) and in subsequent lines regardless of PD-L1 status. Recently, the combination of Pembrolizumab with platinum salts and pemetrexed has become the gold standard for the first-line treatment in patients with PD-L1 expression <50%. Data on the optimal duration of immunotherapy are scarce, especially considering that the onset of immune-related adverse events (irAE) has also been reported after several months of treatment and the long-term effects of the persistent immune system stimulation are unknown. Furthermore, predictive factors are not available to identify those patients who will respond to treatment and could benefit from a shorter duration of therapy -this information is pivotal to minimize the risk of side effects and improve the quality of life. Basal characteristics, such as PD-L1 expression, percentage of Cluster of Differentiation 8 (CD-8) + T-lymphocyte in tumor-infiltrating lymphocytes (TILs), mutational status, neutrophil to lymphocyte ratio (NLR), and platelets to lymphocytes ratio (PLR) have been reported as possible biomarkers, but further data are needed to confirm their predictive value. The purpose of the study is to identify the differences in terms of effectiveness and safety of immunotherapy in long-responder patients in the two cohorts. Secondary objectives are to evaluate the outcome after anti-PD1/PD-L1 rechallenge or other treatment for patients who progress after immunotherapy discontinuation and to identify baseline characteristics that may be predictive of response (molecular characteristics, biohumoral parameters, body mass index).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: November 30, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years

2. Histologically / cytologically confirmed diagnosis of NSCLC, with or without brain metastases

3. Illness measurable according to Response Evaluation Criteria in Solid Tumours (iRECIST) criteria

4. At least 24 months of treatment with Pembrolizumab, Nivolumab or Atezolizumab

5. Complete response (CR)/ partial response (RP)/ stable disease at the end of 24-month treatment. The maintenance of the response may also have been obtained after loco-regional treatment, e.g. surgery or radiotherapy, in the case of oligoprogression for a maximum of 3 locoregional treatments (e.g. radiotherapy, surgery) throughout the period of treatment and suspension. Even progression at the brain level, treated with radiation therapy or surgery, can be considered, provided that it is followed by a disease control for at least 3 months.

6. At least 3 months of follow-up or death within three months after stopping the 24-month treatment.

7. Informed consent freely granted and acquired before the start of the study, for alive and contactable patients.

Exclusion Criteria:

1. Initial chemo-immunotherapy treatment or association with other immunotherapy or other drugs in the context of clinical trials.

2. Permanent discontinuation of treatment with anti PD-1 / PD-L1 for adverse events.

3. More than 3 loco-regional treatments for maintaining the radiological response

4. Suspension of immunotherapy for a period longer than 40 days during the 24-month treatment.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer

Intervention

Drug:
• Immunotherapy
At least 24 months with Pembrolizumab, Nivolumab or Atezolizumab in any treatment line

Locations

Country	Name	City	State
Italy	AOU Ospedali Riuniti	Ancona
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	Ospedale Policlinico San Martino	Genova
Italy	Azienda Ospedaliero Universitaria	Modena
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza
Italy	Istituto Nazionale dei Tumori	Napoli
Italy	Azienda Ospedaliero Universitaria San Luigi	Orbassano
Italy	Azienda Ospedaliero Universitaria	Parma
Italy	Azienda Ospedaliera Marche Nord	Pesaro
Italy	Azienda Sanitaria Universitaria Friuli Centrale	Udine

Sponsors (2)

Lead Sponsor	Collaborator
University of Milano Bicocca	Azienda Ospedaliera San Gerardo di Monza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free survival	Progression free survival (PFS) in the two cohorts; at least 24 months with Pembrolizumab, Nivolumab or Atezolizumab in any treatment line	Through study completion, an average of 18 months
Primary	Overall survival	Overall survival (OS) in the two cohorts; OS will be calculated from the first day of treatment until the date of death from any cause.	Through study completion, an average of 18 months
Primary	Percentage of patients with disease progression after 24 months of treatment	Proportion of patients who show disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria	Through study completion, an average of 18 months