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

Neoplasms Clinical Trial

— AcceleRET-Lung  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04222972
• Other study ID #: BO42864
• Secondary ID: 2019-002463-10BL
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 24, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 223
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Pralsetinib
Administered orally
• Carboplatin
Administered IV
• Cisplatin
Administered IV
• Pemetrexed
Administered IV
• Pembrolizumab
Administered IV
• Gemcitabine
Administered IV
• Paclitaxel
Administered IV
• Nab-Paclitaxel
Administered IV

Locations

Country	Name	City	State
Argentina	Hospital Britanico; Oncologia	Buenos Aires
Argentina	Centro Oncologico Korben; Oncology	Ciudad Autonoma Buenos Aires
Argentina	Centro Oncologico Riojano Integral (CORI)	La Rioja
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Royal North Shore Hospital; Department of Medical Oncology	St Leonards	New South Wales
Belgium	UZ Antwerpen	Edegem
Brazil	Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda	Ijui	RS
Brazil	Liga Norte Riograndense Contra O Câncer	Natal	RN
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Hospital A. C. Camargo; Oncologia	Sao Paulo	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Costa Rica	Clinica CIMCA	San José
France	Institut Bergonie CLCC Bordeaux	Bordeaux
France	Hôpital Ambroise Paré - Boulogne-Billancourt	Boulogne Billancourt
France	Hôpital Louis Pradel, Hospices Civils de Lyon	Bron
France	CHRU Lille Service de Pneumologie et Oncologie Thoracique	Lille
France	Institut Paoli Calmettes; Oncologie Medicale	Marseille
France	Hopital Bichat Claude Bernard; Oncologie Serv.	Paris
France	Hopital Tenon;Pneumologie	Paris
France	Hopital de Pontchaillou; Service de Pneumologie	Rennes
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	CHU Strasbourg - Nouvel Hopital Civil	Strasbourg
France	CHU de Toulouse - Hôpital Larrey; Service de pneumologie et oncologie pneumologique	Toulouse cedex 9
France	Institut Gustave Roussy; Departement Oncologie Medicale	Villejuif
Germany	Universitätsklinikum Carl Gustav Carus, Medizinische Klinik I, Pneumologie MK1-A13	Dresden
Germany	Asklepios-Fachkliniken Muenchen-Gauting; Onkologie	Gauting
Germany	Pius-Hospital; Klinik fuer Haematologie und Onkologie	Oldenburg
Germany	Leopoldina-Krankenhaus Medizinische Klinik II	Schweinfurt
Germany	Klinik Schillerhöhe; Pneumologische Onkologie	Stuttgart
Ireland	St. James Hospital; Oncology	Dublin
Italy	IRCCS Giovanni Paolo II Istituto Oncologico	Bari	Puglia
Italy	Ospedale Clinicizzato SS Annunziata	Chieti	Abruzzo
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Italy	Irccs Ospedale San Raffaele	Milano	Lombardia
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Italy	Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare	Pisa	Toscana
Italy	Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica	Ravenna	Emilia-Romagna
Italy	AZ. Ospedaliera San Giovanni - Addolorata	Roma	Lazio
Italy	Istituto Nazionale Tumori Regina Elena	Roma	Lazio
Italy	A.O.U. INTEGRATA DI VERONA-Ospedale Civile Maggiore Borgo Trento; U.O.C. Oncologia	Verona	Veneto
Japan	Nagoya University Hospital	Aichi
Japan	Hirosaki University Hospital	Aomori
Japan	Ehime University Hospital	Ehime
Japan	Kyushu University Hospital	Fukuoka
Japan	National Hospital Organization Himeji Medical Center	Hyogo
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kansai Medical University Hospital	Osaka
Japan	Osaka City General Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Juntendo University Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	National Hospital Organization Yamaguchi - Ube Medical Center	Yamaguchi
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Netherlands	NKI/AvL	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Maastricht University Medical Center	Maastricht
Norway	Oslo universitetssykehus HF, Ullevål, Kreftsenteret	Oslo
Panama	Hemato Oncología de Panamá Especializada	Panama City
Poland	Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers	Warszawa
Portugal	Hospital Garcia de Orta; Servico de Pneumologia	Almada
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Portugal	Centro Hospitalar de Vila Nova de Gaia / Espinho E.P.E	Vila Nova de Gaia
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña	LA Coruña
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clínic. Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Insititut Catala D'Oncologia	Hospitalet de Llobregat	Barcelona
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital Univ. Central de Asturias; Servicio de Oncologia	Oviedo	Asturias
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital General Universitario de Valencia; Servicio de oncologia	Valencia
Spain	Hosp Clinico Univ Lozano Blesa; División De Oncología Médica	Zaragoza
Sweden	Karolinska Universitetssjukhuset, Solna; Kliniska prövningsenheten Z:4:01	Stockholm
Switzerland	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich
Turkey	Adana Baskent University Hospital; Medical Oncology	Adana
Turkey	Adana City Hospital, Medical Oncology	Adana
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Medipol Mega Üniversite Hastanesi Göztepe	Istanbul
Turkey	?zmir Medical Point; Oncology	Kar?iyaka
Turkey	Medical Park Seyhan Hospital; Oncology Department	Seyhan
United Kingdom	Velindre Cancer Centre; Oncology Dept	Cardiff
United Kingdom	Leicester Royal Infirmary; Dept. of Medical Oncology	Leicester
United Kingdom	Guys & St Thomas Hospital; Department of Oncology	London
United Kingdom	Royal Marsden Hospital; Dept of Med-Onc	London
United Kingdom	University College Hospital; Department of Oncology	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United Kingdom	Royal Marsden Hospital; Dept of Medical Oncology	Sutton
United States	UC Irvine Medical Center	Orange	California
United States	Southern California Kaiser Permanente	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Costa Rica,  France,  Germany,  Ireland,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Panama,  Poland,  Portugal,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	Defined as the time from randomisation date to the first documented progressive disease (PD), as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurs first.	Estimated at up to 32 months
Secondary	Overall Response Rate (ORR)	Defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) on two consecutive occasions = 4 weeks apart, as assessed by investigator according to RECIST 1.1.	Estimated at up to 32 months
Secondary	Overall Survival (OS)	Defined as the time from randomisation date to death due to any cause.	Estimated at approximately 32 months
Secondary	Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	The intensity of Adverse Events (AEs) will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0).	Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)
Secondary	Changes in Eastern Cooperative Oncology Group Performance Status (ECOG PS)	Further characterising safety and tolerability.	Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)
Secondary	Duration of Response (DOR)	Defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as assessed by investigator according to RECIST v1.1.	Estimated at up to 32 months
Secondary	Clinical Benefit Rate (CBR)	Defined as the proportion of participants who experience a best response of Stable Disease (SD) with a minimum duration of 6 months, a CR, or a PR, as assessed by investigator according to RECIST v1.1.	Estimated at up to 32 months
Secondary	Disease Control Rate (DCR)	Defined as the proportion of participants who experience a best response of CR, or PR, or SD, as assessed by investigator according to RECIST v1.1.	Estimated at up to 32 months