External Control, Observational, Retrospective Study Comparing Pralsetinib to Best Available Therapy in Patients With RET-Fusion Positive NSCLC

Study Overview
=================
Brief Summary
-----------------
This is an external control, observational, retrospective study designed to compare clinical outcomes for pralsetinib compared with best available therapy for patients with RET-fusion positive advanced NSCLC.

Official Title
-----------------
An External Control, Observational, Retrospective Study Assessing the Effect of Pralsetinib Compared With Best Available Therapy for Patients With RET-Fusion Positive Advanced Non-Small Cell Lung Cancer

Conditions
-----------------
Lung Neoplasm, RET-fusion Non Small Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Diseases, Head and Neck Neoplasms, Carcinoma, Neoplasms by Histologic Type, Neoplasms, Germ Cell and Embryonal, Neoplasms, Nerve Tissue, Metastatic Non Small Cell Lung Cancer

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must have a diagnosis of locally advanced (non-resectable) or metastatic RET-fusion positive NSCLC Must have received at least one line of systemic therapy for locally advanced (non-resectable) or metastatic RET-fusion positive NSCLC, which may include regimens containing: Chemotherapy, e.g., regimens containing platinum doublet-based therapy (carboplatin, cisplatin) Chemotherapy in combination with other drugs will be assessed, e.g., in combination with pemetrexed, immune checkpoint inhibitors (pembrolizumab), bevacizumab Ramucirumab in combination with docetaxel Immune checkpoint inhibitors, e.g., pembrolizumab, nivolumab, and atezolizumab MKIs, e.g., cabozantinib, alectinib, vandetanib, sunitinib, and nintedanib Must be aged ≥18 years of age at the initiation of first systemic line of therapy Must have availabile of performance status (e.g., Eastern Cooperative Oncology Group [ECOG] score or Karnofsky score) Must have an index date at least 3 months prior to the start of data collection (in order to include patients with at least 3 months of follow-up after index date), unless date of death occurred less than three months from index date Must have an approved waiver of informed consent or signed informed consent for participation in the retrospective chart review study, as applicable Exclusion Criteria: Known primary driver alteration other than RET (e.g., targetable mutation in EGFR, ALK, ROS1, or BRAF) History of other malignancy, other than non-melanoma skin cancer, within 1 year prior to initiation of first systemic therapy Received pralsetinib as the first line of systemic therapy for RET-fusion positive NSCLC, or prior to initiation of first systemic therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients from the BLU-667-1101 (ARROW) study<br>Patients with Non-Small Cell Lung Cancer (NSCLC) who received treatment with pralsetinib as part of the BLU-667-1101 (ARROW) study | |
| External Control Group<br>Patients with Non-Small Cell Lung Cancer (NSCLC) that received best available therapy | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative evaluation of real-world response rate (rwORR) between patients receiving best available therapy versus pralsetinib | rwORR, defined as the proportion of patients with clinician-assess complete response (CR) or partial response (PR) | Up to 12 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative evaluation between patients receiving best available therapy versus pralsetinib of Overall survival (OS) | OS, defined as time from initiation of a given line of therapy to death from any cause | Up to 12 years | 
| Comparative evaluation between patients receiving best available therapy versus pralsetinib of Real-world duration of response (rwDOR) | rwDOR, defined as the duration of time from the first documented clinician-assessed response to the first documented clinician-assessed progressive disease or death due to any cause within 30 days of the last radiological exam, for each line of treatment | Up to 12 years | 
| Comparative evaluation between patients receiving best available therapy versus pralsetinib of Real-world disease control rate (rwDCR) | rwDCR, defined as proportion of patients with clinician-assessed complete response, partial response, or stable disease | Up to 12 years | 
| Comparative evaluation between patients receiving best available therapy versus pralsetinib of Real-world clinical benefit rate (rwCBR) | rwCBR, defined as proportion of patients who had documented clinician-assessed complete response or partial response, or stable disease lasting at least 16 weeks | Up to 12 years | 
| Comparative evaluation between patients receiving best available therapy versus pralsetinib of Real-world progression-free survival (rwPFS) | rwPFS, defined as time from initiation of line of therapy to clinician-assessed disease progression or death from any cause, whichever occurs first | Up to 12 years | 
| Comparative evaluation between patients receiving best available therapy versus pralsetinib of Duration of treatment (DOT) | DOT, defined as time from initiation of line of systemic treatment to discontinuation of same line of treatment for any reason | Up to 12 years | 
| Comparative evaluation between patients receiving best available therapy versus pralsetinib of Time to next treatment line (TtNTL) | TtNTL, defined as the time from initiation of line of systemic treatment to the initiation of the next line of treatment | Up to 12 years | 
| To characterize the safety profile and conduct comparative evaluation of safety between patients receiving best available care vs. pralsetinib | Adverse events (AEs) that result in treatment modification or discontinuation, hospitalization, or death according to evaluation of responsible physician | Up to 12 years |