Clinical trial NCT04222972: A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
Official title: A Phase III, Randomized, Open-Label Study of Pralsetinib Versus Standard of Care for First-Line Treatment of RET Fusion-Positive, Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Keywords: Advanced Non-Small Cell Lung Cancer
RET Lung
RET Mutation
RET Alteration
RET Positive
RET Inhibitor
RET Altered
RET Rearrangement
RET NSCLC
RET-Rearranged NSCLC
RET Fusion
RET Fusion Lung Cancer
M918T
TRIM33-RET
Lung Cancer Mutation
BLU 667
Pralsetinib
RET Tyrosine Kinase
RET Gene Mutation
RET Kinase
Advanced Lung Cancer
Metastatic Lung Cancer
KIF5B-RET
CCDC6-RET
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-01-10
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Estimated at up to 32 months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Estimated at up to 32 months
measure: Overall Survival (OS)
timeFrame: Estimated at approximately 32 months
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)
measure: Changes in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
timeFrame: Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)
measure: Duration of Response (DOR)
timeFrame: Estimated at up to 32 months
measure: Clinical Benefit Rate (CBR)
timeFrame: Estimated at up to 32 months
measure: Disease Control Rate (DCR)
timeFrame: Estimated at up to 32 months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital Britanico
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Hospital A. C. Camargo
state: São Paulo
city: San Jose
country: Costa Rica
facility: Clinica CIMCA
city: Bordeaux
country: France
facility: Institut Bergonie CLCC Bordeaux
city: Boulogne Billancourt
country: France
facility: Hôpital Ambroise Paré - Boulogne-Billancourt
city: Lille
country: France
facility: CHRU Lille Service de Pneumologie et Oncologie Thoracique
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Paris
country: France
facility: Hopital Bichat Claude Bernard
city: Paris
country: France
facility: Hopital Tenon
city: Rennes
country: France
facility: Hopital de Pontchaillou
city: Strasbourg
country: France
facility: CHU Strasbourg - Nouvel Hopital Civil
city: Toulouse cedex 9
country: France
facility: CHU de Toulouse - Hôpital Larrey
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus, Medizinische Klinik I, Pneumologie MK1-A13
city: Gauting
country: Germany
facility: Asklepios-Fachkliniken Muenchen-Gauting
city: Oldenburg
country: Germany
facility: Pius-Hospital
city: Schweinfurt
country: Germany
facility: Leopoldina-Krankenhaus Medizinische Klinik II
city: Stuttgart
country: Germany
facility: Klinik Schillerhöhe
city: Dublin
country: Ireland
facility: St. James Hospital
city: Chieti
country: Italy
facility: Ospedale Clinicizzato SS Annunziata
state: Abruzzo
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
state: Campania
city: Ravenna
country: Italy
facility: Ospedale Provinciale Santa Maria Delle Croci
state: Emilia-Romagna
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
state: Lazio
city: Roma
country: Italy
facility: AZ. Ospedaliera San Giovanni - Addolorata
state: Lazio
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello
state: Toscana
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto - IRCCS
state: Veneto
city: Verona
country: Italy
facility: A.O.U. INTEGRATA DI VERONA-Ospedale Civile Maggiore Borgo Trento
state: Veneto
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hyogo
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Osaka
country: Japan
facility: Kansai Medical University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Yamaguchi
country: Japan
facility: National Hospital Organization Yamaguchi - Ube Medical Center
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Amsterdam
country: Netherlands
facility: NKI/AvL
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Panama City
country: Panama
facility: Hemato Oncología de Panamá Especializada
city: Warszawa
country: Poland
facility: Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
city: Porto
country: Portugal
facility: IPO do Porto
city: Hospitalet de Llobregat
country: Spain
facility: Insititut Catala D'Oncologia
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
state: LA Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital de Madrid Norte Sanchinarro- Centro Integral Oncologico Clara Campal
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Zaragoza
country: Spain
facility: Hosp Clinico Univ Lozano Blesa
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Solna
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
city: Adana
country: Turkey
facility: Adana City Hospital, Medical Oncology
city: Ankara
country: Turkey
facility: Ankara Bilkent City Hospital
city: Kar?iyaka
country: Turkey
facility: ?zmir Medical Point
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Guys & St Thomas Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: