Lung Cancer Clinical Trial

Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

Summary

This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of pralsetinib (BLU-667) administered orally in participants with medullary thyroid cancer (MTC), RET-altered NSCLC and other RET-altered solid tumors.

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Full Description

The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase 2). Both parts will enroll participants with advanced non-resectable NSCLC, advanced non-resectable thyroid cancer and other advanced solid tumors that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or the participants must be intolerant to or the Investigator has determined that treatment with standard therapy is not appropriate, or there must be no accepted standard therapy for their disease.

View Eligibility Criteria

Eligibility Criteria

Key Inclusion Criteria:

Diagnosis during dose escalation (Phase 1) - Pathologically documented, definitively diagnosed non-resectable advanced solid tumor.

All participants treated at doses > 120 mg per day must have MTC, or a RET-altered solid tumor per local assessment of tumor tissue and/or blood.

Diagnosis during dose expansion (Phase 2) - All participants (with the exception of participants with MTC enrolled in Groups 3, 4, and 9) must have an oncogenic RET-rearrangement/fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor, as determined by local or central testing of tumor or circulating tumor nucleic acid in blood; as detailed below.

Group 1 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion previously treated with a platinum-based chemotherapy.
Group 2 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion not previously treated with a platinum-based chemotherapy, including those who have not had any systemic therapy. Prior platinum chemotherapy in the neoadjuvant and adjuvant setting is permitted if the last dose of platinum was 4 months or more before the first dose of study drug.
Group 3 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit and was previously treated with cabozantinib and/or vandetanib.
Group 4 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit and was not previously treated with cabozantinib and/or vandetanib.
Group 5 - participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion, have previously received standard of care (SOC) appropriate for their tumor type (unless there is no accepted standard therapy for the tumor type or the Investigator has determined that treatment with standard therapy is not appropriate), and must not have been eligible for any of the other groups.
Group 6 - participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion or mutation that was previously treated with a selective tyrosine kinase inhibitor (TKI) that inhibits RET
Group 7 - participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET mutation previously treated with SOC appropriate for the tumor type and not eligible for any of the other groups
Group 8 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion that was previously treated with a platinum based chemotherapy (China only).
Group 9 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit, and was not previously treated with systemic therapy (except prior cytotoxic chemotherapy is allowed) for advanced or metastatic disease (China only).
Participants must have non-resectable disease.
Dose expansion (Phase 2): Participants in all groups (except Group 7) must have measurable disease per RECIST v1.1 (or RANO, criteria if appropriate for tumor type).
Participants agrees to provide tumor tissue (archived, if available or a fresh biopsy) for RET status confirmation and is willing to consider an on-treatment tumor biopsy, if considered safe and medically feasible by the treating Investigator. For Phase 2, Group 6, participants are required to undergo a pretreatment biopsy to define baseline RET status in tumor tissue.
Participants has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.

Key Exclusion Criteria:

Participant's cancer has a known primary driver alteration other than RET. For example, NSCLC with a targetable mutation in EGFR, ALK, ROS1 or BRAF; colorectal with an oncogenic KRAS, NRAS, or BRAF mutation.

Participants had any of the following within 14 days prior to the first dose of study drug:

Platelet count < 75 × 10^9/L.
Absolute neutrophil count < 1.0 × 10^9/L.
Hemoglobin < 9.0 g/dL (red blood cell transfusion and erythropoietin may be used to reach at least 9.0 g/dL, but must have been administered at least 2 weeks prior to the first dose of study drug.
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) if no hepatic metastases are present; > 5 × ULN if hepatic metastases are present.
Total bilirubin > 1.5 × ULN; > 3 × ULN with direct bilirubin > 1.5 × ULN in presence of Gilbert's disease.
Estimated (Cockcroft-Gault formula) or measured creatinine clearance < 40 mL/min.
Total serum phosphorus > 5.5 mg/dL
QT interval corrected using Fridericia's formula (QTcF) > 470 msec or history of prolonged QT syndrome or Torsades de pointes, or familial history of prolonged QT syndrome.
Clinically significant, uncontrolled, cardiovascular disease.
Central nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms.
Clinically symptomatic interstitial lung disease or interstitial pneumonitis including radiation pneumonitis
Participants in Groups 1-5 and 7 (Phase 2) previously treated with a selective RET inhibitor
Participant had a major surgical procedure within 14 days of the first dose of study drug
Participant had a history of another primary malignancy that had been diagnosed or required therapy within the a year prior to the study
Pregnant or breastfeeding female participants

Study is for people with:

Lung Cancer

Phase:

Phase 1

Estimated Enrollment:

589

Study ID:

NCT03037385

Recruitment Status:

Active, not recruiting

Sponsor:

Hoffmann-La Roche

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There are 64 Locations for this study

See Locations Near You

Mayo Clinic Hospital
Phoenix Arizona, 85054, United States
UC Irvine Medical Center
Orange California, 92868, United States
University of Colorado Anschutz Medical Campus
Aurora Colorado, 80045, United States
Georgetown University Medical Center
Washington District of Columbia, 20007, United States
Mayo Clinic-Jacksonville
Jacksonville Florida, 32224, United States
Sylvester Comprehensive Cancer Center; University of Miami School of Medicine
Miami Florida, 33136, United States
Maryland Oncology Hematology, P.A.
Columbia Maryland, 21044, United States
Massachusetts General Hospital.
Boston Massachusetts, 02114, United States
University of Michigan
Ann Arbor Michigan, 48109, United States
Mayo Clinic Rochester
Rochester Minnesota, 55902, United States
Washington University School of Medicine in St. Louis
Saint Louis Missouri, 63110, United States
Albany Medical Center
Albany New York, 12208, United States
Weill Cornell Medical College-New York Presbyterian Hospital
New York New York, 10021, United States
Oregon Health & Science University
Portland Oregon, 97239, United States
Stellar - Chance Laboratories
Philadelphia Pennsylvania, 19104, United States
Texas Oncology-Austin Midtown
Austin Texas, 78705, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas Texas, 75246, United States
The University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States
Seattle Cancer Care Alliance
Seattle Washington, 98109, United States
Beijing Cancer Hospital
Beijing , 10014, China
The affiliated Cancer Hospital, School of Medicine, UESTC
Chengdu , 61004, China
West China Hospital, Sichuan University
Chengdu , 61004, China
Chongqing Cancer Hospital
Chongqing , 40003, China
Fujian Provincial Cancer Hospital
Fuzhou City , 35001, China
First Affiliated Hospital of Gannan Medical University
Ganzhou , 34100, China
Sun Yet-sen University Cancer Center
Guangzhou City , 51066, China
Guangdong General Hospital
Guangzhou , 51008, China
Zhejiang Provincial People's Hospital
Hangzhou , 31001, China
Jinan Central Hospital
Jinan City , 25001, China
Gansu Cancer Hospital
Lanzhou , 73005, China
Fudan University Shanghai Cancer Center
Shanghai City , 20012, China
Tianjin Medical University Cancer Institute & Hospital
Tianjing , 30006, China
Tianjin Cancer Hospital
Tianjin , 30006, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan City , 43002, China
Zhejiang Cancer Hospital
Zhejiang , 31002, China
Henan Cancer Hospital
Zhengzhou , 45000, China
Hôpital Larrey;Université Paul Sabatier
Toulouse , 31059, France
Helios Klinikum Emil von Behring GmbH
Berlin , 14165, Germany
Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
Essen , 45122, Germany
Thoraxklinik Heidelberg gGmbH
Heidelberg , 69126, Germany
Klinikum der Universität München
Muenchen , 80336, Germany
Pius-Hospital; Klinik fuer Haematologie und Onkologie
Oldenburg , 26121, Germany
The Chinese University of Hong Kong
Shatin , 12345, Hong Kong
Ospedale Santa Maria Delle Croci
Ravenna Emilia-Romagna, 48100, Italy
Istituto Nazionale Tumori Regina Elena
Roma Lazio, 00144, Italy
IEO; Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative
Milano Lombardia, 20141, Italy
Asst Grande Ospedale Metropolitano Niguarda
Milano Lombardia, 20162, Italy
Seoul National University Hospital
Seoul , 03080, Korea, Republic of
Asan Medical Center
Seoul , 05505, Korea, Republic of
Samsung Medical Center
Seoul , 06351, Korea, Republic of
Severance Hospital, Yonsei University Health System; Oncology
Seoul , 120-7, Korea, Republic of
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam , 1066 , Netherlands
Universitair Medisch Centrum Groningen
Groningen , 9713 , Netherlands
National Cancer Centre
Singapore , 16961, Singapore
Institut Catala d Oncologia Hospitalet
Hospitalet de Llobregat Barcelona, 08908, Spain
Vall d´Hebron Institute of Oncology (VHIO), Barcelona
Barcelona , 08035, Spain
Hospital Clinic de Barcelona
Barcelona , 08036, Spain
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid , 28034, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Madrid , 28041, Spain
Taipei Veterans General Hospital
Taipei City , 11217, Taiwan
National Taiwan University Hospital
Taipei , 10002, Taiwan
Aberdeen Royal Infirmary
Aberdeen , AB25 , United Kingdom
Guys and St Thomas NHS Foundation Trust, Guys Hospital
London , SE1 9, United Kingdom
Sarah Cannon Research Institute
London , W1G 6, United Kingdom
University College London Hospitals NHS Foundation Trust; NIHR UCLH Clinical Research Facility
London , W1T 7, United Kingdom
The Christie NHS Foundation Trust
Manchester , M20 4, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 1

Estimated Enrollment:

589

Study ID:

NCT03037385

Recruitment Status:

Active, not recruiting

Sponsor:


Hoffmann-La Roche

How clear is this clinincal trial information?

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