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

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

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.

Study Overview

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

• Study Type: Observational
• Enrollment (Anticipated): 279

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31300
    • University Hospital Center of Toulouse - Larrey Hospital
• Switzerland
  • Lucerne, Switzerland, 6000
    • Lucerne Cantonal Hospital
• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

This study will include patients with locally advanced or metastatic RET-fusion positive non-small cell lung cancer (NSCLC)

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients from the BLU-667-1101 (ARROW) study; 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; 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

Collaborators and Investigators

• Sponsor: Blueprint Medicines Corporation
• Collaborators: Analysis Group, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): October 31, 2021
• Study Completion (Anticipated): October 31, 2021

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: January 4, 2021
• First Posted (Actual): January 6, 2021

Study Record Updates

• Last Update Posted (Actual): August 10, 2021
• Last Update Submitted That Met QC Criteria: August 9, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Glandular and Epithelial; Bronchial Neoplasms; Neoplasms; Neoplasms, Germ Cell and Embryonal; Head and Neck Neoplasms; Lung Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Respiratory Tract Diseases; Neoplasms by Site; Neoplasms by Histologic Type; Thoracic Neoplasms; Carcinoma, Bronchogenic; Respiratory Tract Neoplasms; Neoplasms, Nerve Tissue; Bronchial Diseases
• Other Study ID Numbers: BLU-667-2404

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No