A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)

NCT ID: NCT04222972

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 223 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-24
• Study Completion Date: 2025-01-27

Brief Summary

This is an international, randomized, open-label, Phase 3 study designed to evaluate whether the potent and selective RET inhibitor, pralsetinib, improves outcomes when compared to a platinum chemotherapy-based regimen chosen by the Investigator from a list of standard of care treatments, as measured primarily by progression free survival (PFS), for participants with RET fusion-positive metastatic NSCLC who have not previously received systemic anticancer therapy for metastatic disease.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pralsetinib

Participants randomized to the Experimental Arm will receive Pralsetinib

Group Type: EXPERIMENTAL

Pralsetinib

Intervention Type: DRUG

Administered orally

Platinum-based chemotherapy with or without pembrolizumab

Participants randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology)

Nonsquamous histology

• Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
• Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.

Squamous histology

• Carboplatin or cisplatin / gemcitabine
• Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Administered IV

Cisplatin

Intervention Type: DRUG

Administered IV

Pemetrexed

Intervention Type: DRUG

Administered IV

Pembrolizumab

Intervention Type: DRUG

Administered IV

Gemcitabine

Intervention Type: DRUG

Administered IV

Paclitaxel

Intervention Type: DRUG

Administered IV

Nab-Paclitaxel

Intervention Type: DRUG

Administered IV

Interventions

Pralsetinib

Administered orally

Intervention Type: DRUG

Carboplatin

Administered IV

Intervention Type: DRUG

Cisplatin

Administered IV

Intervention Type: DRUG

Pemetrexed

Administered IV

Intervention Type: DRUG

Pembrolizumab

Administered IV

Intervention Type: DRUG

Gemcitabine

Administered IV

Intervention Type: DRUG

Paclitaxel

Administered IV

Intervention Type: DRUG

Nab-Paclitaxel

Administered IV

Intervention Type: DRUG

Other Intervention Names

BLU-667

Eligibility Criteria

Inclusion Criteria

• Participant has pathologically confirmed, definitively diagnosed, locally advanced (not able to be treated with surgery or radiotherapy) or metastatic NSCLC and has not been treated with systemic anticancer therapy for metastatic disease.
• Participant must have a documented RET-fusion
• Participant has measurable disease based on RECIST 1.1 as determined by the local site Investigator/radiology assessment.
• Participant has an ECOG Performance Status of 0 or 1.
• Participant should not have received any prior anticancer therapy for metastatic disease.

• Participants can have received previous anticancer therapy (except a selective RET inhibitor) in the neoadjuvant or adjuvant setting but must have experienced an interval of at least ≥ 6 months from completion of therapy to recurrence.
• Participants that received previous immune checkpoint inhibitors in the adjuvant or consolidation following chemoradiation are not allowed to receive pembrolizumab if randomized in Arm B
• Participant is an appropriate candidate for and agrees to receive 1 of the Investigator choice platinum-based chemotherapy regimens if randomized to Arm B.
• For women of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception.
• For men: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use a condom and agree to refrain from donating sperm.

Exclusion Criteria

• Participant's tumor has any additional known primary driver alterations other than RET, such as targetable mutations of EGFR, ALK, ROS1, MET, and BRAF. Investigators should discuss enrollment with Sponsor designee regarding co-mutations.
• Participant previously received treatment with a selective RET inhibitor.
• Participant received radiotherapy or radiosurgery to any site within 14 days before randomization or more than 30 Gy of radiotherapy to the lung in the 6 months before randomization.
• Participant with a history of pneumonitis within the last 12 months.
• Participant has CNS metastases or a primary CNS tumor that is associated with progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease. If a participant requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks before Cycle 1 Day 1.
• Participant has had a history of another primary malignancy that has been diagnosed or required therapy within the past 3 years prior to randomization.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Hospital Britanico

Buenos Aires, , Argentina

Royal North Shore Hospital

St Leonards, New South Wales, Australia

UZ Antwerpen

Edegem, , Belgium

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital A. C. Camargo

São Paulo, São Paulo, Brazil

Clinica CIMCA

San José, , Costa Rica

Institut Bergonie CLCC Bordeaux

Bordeaux, , France

Hôpital Ambroise Paré - Boulogne-Billancourt

Boulogne-Billancourt, , France

CHRU Lille Service de Pneumologie et Oncologie Thoracique

Lille, , France

Institut Paoli Calmettes

Marseille, , France

Hopital Bichat Claude Bernard

Paris, , France

Hopital Tenon

Paris, , France

Hopital de Pontchaillou

Rennes, , France

CHU Strasbourg - Nouvel Hopital Civil

Strasbourg, , France

CHU de Toulouse - Hôpital Larrey

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Universitätsklinikum Carl Gustav Carus, Medizinische Klinik I, Pneumologie MK1-A13

Dresden, , Germany

Asklepios-Fachkliniken Muenchen-Gauting

Gauting, , Germany

Pius-Hospital

Oldenburg, , Germany

Leopoldina-Krankenhaus Medizinische Klinik II

Schweinfurt, , Germany

Klinik Schillerhöhe

Stuttgart, , Germany

St. James Hospital

Dublin, , Ireland

Ospedale Clinicizzato SS Annunziata

Chieti, Abruzzo, Italy

Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale

Napoli, Campania, Italy

Ospedale Provinciale Santa Maria Delle Croci

Ravenna, Emilia-Romagna, Italy

Istituto Nazionale Tumori Regina Elena

Rome, Lazio, Italy

AZ. Ospedaliera San Giovanni - Addolorata

Rome, Lazio, Italy

Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello

Pisa, Tuscany, Italy

IOV - Istituto Oncologico Veneto - IRCCS

Padua, Veneto, Italy

A.O.U. INTEGRATA DI VERONA-Ospedale Civile Maggiore Borgo Trento

Verona, Veneto, Italy

Kyushu University Hospital

Fukuoka, , Japan

National Hospital Organization Himeji Medical Center

Hyōgo, , Japan

Osaka International Cancer Institute

Osaka, , Japan

Kansai Medical University Hospital

Osaka, , Japan

Juntendo University Hospital

Tokyo, , Japan

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

National Hospital Organization Yamaguchi - Ube Medical Center

Yamaguchi, , Japan

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), Mexico

NKI/AvL

Amsterdam, , Netherlands

Maastricht University Medical Center

Maastricht, , Netherlands

Hemato Oncología de Panamá Especializada

Panama City, , Panama

Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad

Warsaw, , Poland

IPO do Porto

Porto, , Portugal

National Cancer Center

Goyang-si, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Insititut Catala D'Oncologia

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Complejo Hospitalario Universitario A Coruña

A Coruña, LA Coruna, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

Hospital de Madrid Norte Sanchinarro- Centro Integral Oncologico Clara Campal

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Hosp Clinico Univ Lozano Blesa

Zaragoza, , Spain

Karolinska Universitetssjukhuset, Solna

Stockholm, , Sweden

UniversitätsSpital Zürich

Zurich, , Switzerland

Adana City Hospital, Medical Oncology

Adana, , Turkey (Türkiye)

Ankara Bilkent City Hospital

Ankara, , Turkey (Türkiye)

?zmir Medical Point

Kar?iyaka, , Turkey (Türkiye)

Velindre Cancer Centre

Cardiff, , United Kingdom

Leicester Royal Infirmary

Leicester, , United Kingdom

University College Hospital

London, , United Kingdom

Guys & St Thomas Hospital

London, , United Kingdom

Royal Marsden Hospital

London, , United Kingdom

Christie Hospital Nhs Trust

Manchester, , United Kingdom

Royal Marsden Hospital

Sutton, , United Kingdom

Countries

Argentina; Australia; Belgium; Brazil; Costa Rica; France; Germany; Ireland; Italy; Japan; Mexico; Netherlands; Panama; Poland; Portugal; South Korea; Spain; Sweden; Switzerland; Turkey (Türkiye); United Kingdom

Other Identifiers

2019-002463-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BLU-667-2303

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-505035-12-00

Identifier Type: OTHER

Identifier Source: secondary_id

BO42864

Identifier Type: -

Identifier Source: org_study_id