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

• Conditions: Carcinoma; Bronchial Diseases; Neoplasms by Histologic Type; Metastatic Non Small Cell Lung Cancer; RET-fusion Non Small Cell Lung Cancer; Lung Neoplasm; Neoplasms by Site; Carcinoma, Bronchogenic; Head and Neck Neoplasms; Respiratory Tract Neoplasms

• Registration Number: NCT04697446
• Lead Sponsor: Blueprint Medicines Corporation

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-01
• Study First Submitted: 2020-12-16
• Study First Submitted QC: 2021-01-04
• Study First Posted: 2021-01-06
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-09
• Last Update Posted: 2021-08-10
• Primary Completion: 2021-10-31
• Study Completion: 2021-10-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 279

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University Hospital Center of Toulouse - Larrey Hospital; 🇫🇷 Toulouse, France

Lucerne Cantonal Hospital; 🇨🇭 Lucerne, Switzerland