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

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

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.

Study Overview

• Status: Terminated
• Conditions: Neoplasms; Neoplasms by Histologic Type; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Germ Cell and Embryonal; Head and Neck Neoplasms; Carcinoma, Non-Small-Cell Lung; Bronchial Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Neoplasms, Nerve Tissue; Respiratory Tract Disease; Lung Neoplasm; RET-fusion Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Gemcitabine; Drug: Pralsetinib; Drug: Nab-Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 223
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
    • Hospital Britanico
  • La Rioja, Argentina, F5300COE
    • Centro Oncologico Riojano Integral (Cori)
• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01509-010
      • Hospital A. C. Camargo
• Costa Rica
  • San José, Costa Rica, 10103
    • Clinica CIMCA
• France
  • Bordeaux, France, 33000
    • Institut Bergonie CLCC Bordeaux
  • Boulogne-Billancourt, France, 92100
    • Hôpital Ambroise Paré - Boulogne-Billancourt
  • Bron, France, 69677
    • Hôpital Louis Pradel, Hospices Civils de Lyon
  • Lille, France, 59000
    • CHRU Lille Service de Pneumologie et Oncologie Thoracique
  • Marseille, France, 13273
    • Institut Paoli Calmettes
  • Paris, France, 75970
    • Hôpital Tenon
  • Paris, France, 75018
    • Hopital Bichat Claude Bernard
  • Rennes, France, 35033
    • Hôpital de Pontchaillou
  • Saint-Herblain, France, 44805
    • Ico Rene Gauducheau
  • Strasbourg, France, 67091
    • CHU Strasbourg - Nouvel Hôpital Civil
  • Toulouse, France, 31100
    • CHU de Toulouse - Hopital Larrey
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus, Medizinische Klinik I, Pneumologie MK1-A13
  • Gauting, Germany, 82131
    • Asklepios-Fachkliniken Muenchen-Gauting
  • Oldenburg, Germany, 26121
    • Pius-Hospital
  • Schweinfurt, Germany, 97422
    • Leopoldina-Krankenhaus Medizinische Klinik II
  • Stuttgart, Germany, 70376
    • Klinik Schillerhöhe
• Ireland
  • Dublin, Ireland, D08 HNY1
    • St. James Hospital
• Italy
  • Abruzzo
    • Chieti, Abruzzo, Italy, 66100
      • Ospedale Clinicizzato SS Annunziata
  • Apulia
    • Bari, Apulia, Italy, 70124
      • IRCCS Giovanni Paolo II Istituto Oncologico
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
  • Emilia-Romagna
    • Ravenna, Emilia-Romagna, Italy, 48100
      • Ospedale Provinciale Santa Maria Delle Croci
  • Lazio
    • Rome, Lazio, Italy, 00184
      • AZ. Ospedaliera San Giovanni - Addolorata
    • Rome, Lazio, Italy, 00144
      • Istituto Nazionale Tumori Regina Elena
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Milan, Lombardy, Italy, 20132
      • Irccs Ospedale San Raffaele
    • Milan, Lombardy, Italy, 20141
      • Istituto Europeo di Oncologia
  • Tuscany
    • Pisa, Tuscany, Italy, 56124
      • Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello
  • Veneto
    • Padua, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto - IRCCS
    • Verona, Veneto, Italy, 37126
      • A.O.U. INTEGRATA DI VERONA-Ospedale Civile Maggiore Borgo Trento
• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Hyōgo, Japan, 670-8520
    • National Hospital Organization Himeji Medical Center
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Osaka, Japan, 573-1191
    • Kansai Medical University Hospital
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital Of JFCR
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Yamaguchi, Japan, 755-0241
    • National Hospital Organization Yamaguchi - Ube Medical Center
• Mexico
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 03100
      • Health Pharma Professional Research
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • NKI/AvL
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Center
• Norway
  • Oslo, Norway, 0450
    • Oslo universitetssykehus HF, Ullevål, Kreftsenteret
• Panama
  • Panama City, Panama, 0801
    • Hemato Oncología de Panamá Especializada
• Poland
  • Warsaw, Poland, 02-781
    • Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
• Portugal
  • Porto, Portugal, 4200-072
    • IPO do Porto
• South Korea
  • Goyang-si, South Korea, 10408
    • National Cancer Center
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebrón
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28050
    • Hospital de Madrid Norte Sanchinarro- Centro Integral Oncologico Clara Campal
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Zaragoza, Spain, 50009
    • Hosp Clinico Univ Lozano Blesa
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Insititut Catala D'Oncologia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • LA Coruna
    • A Coruña, LA Coruna, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña
• Sweden
  • Stockholm, Sweden, 171 76
    • Karolinska Universitetssjukhuset, Solna
• Switzerland
  • Zurich, Switzerland, 8091
    • UniversitätsSpital Zürich
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01060
    • Adana City Hospital, Medical Oncology
  • Ankara, Turkey (Türkiye), 06490
    • Ankara Bilkent City Hospital
  • Kar?iyaka, Turkey (Türkiye), 35575
    • ?zmir Medical Point
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
  • London, United Kingdom, SE1 9RT
    • Guys & St Thomas Hospital
  • Manchester, United Kingdom, M2O 4BX
    • Christie Hospital Nhs Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pralsetinib; Participants randomized to the Experimental Arm will receive Pralsetinib	Drug: Pralsetinib; Administered orally; Other Names: BLU-667
Active Comparator: 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	Drug: Pembrolizumab; Administered IV; Drug: Paclitaxel; Administered IV; Drug: Carboplatin; Administered IV; Drug: Cisplatin; Administered IV; Drug: Pemetrexed; Administered IV; Drug: Gemcitabine; Administered IV; Drug: Nab-Paclitaxel; Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm A vs Arm B: Treatment Period: Progression-free Survival (PFS)	PFS was defined as the time from randomization to the date of first documented PD as determined by the investigator with the use of Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 millimeters (mm). Kaplan-Meier (K-M) method was used to estimate median PFS. 95% CI for median was computed using the method of Brookmeyer and Crowley.	Up to approximately 50 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm A vs Arm B: Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. 95% CI for rates were constructed using the Clopper-Pearson method. Percentages have been rounded off.	Up to approximately 50 months
Arm A vs Arm B: Overall Survival (OS)	OS was defined as the time from randomization to death from any cause. K-M method was used to estimate median OS. 95% CI for median was computed using the method of Brookmeyer and Crowley.	From randomization to death (up to approximately 50 months)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.	Up to approximately 50 months
Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score	ECOG is a 6-point scale (0-5) used to assess participants functional status, where, 0= Fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity but ambulatory & able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2= ambulatory & capable of all self-care but unable to carry out any work activities. Up & about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead.	Baseline up to 50 months
Arm A vs Arm B: Duration of Response (DOR)	DOR was defined as the time from the first occurrence of a documented objective response (OR) to PD or death from any cause, whichever occurred first, as determined by the investigator with the use of RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. K-M method was used to estimate median DOR. 95% CI for median was computed using the method of Brookmeyer and Crowley.	Up to approximately 50 months
Arm A vs Arm B: Clinical Benefit Rate (CBR)	CBR was defined as the percentage of participants who experienced the best response of stable disease (SD) with a minimum duration of 6 months, a CR, or a PR, as assessed by investigator with use of RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 95% CI for rates were constructed using the Clopper-Pearson method. Percentages are rounded off.	Up to approximately 50 months
Arm A vs Arm B: Disease Control Rate (DCR)	DCR was defined as the percentage of participants who experienced the best response of CR, or PR, or SD, as assessed by investigator according to RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 95% CI for rates were constructed using the Clopper-Pearson method. Percentages are rounded off.	Up to approximately 50 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2020
• Primary Completion (Actual): January 27, 2025
• Study Completion (Actual): January 27, 2025

Study Registration Dates

• First Submitted: January 3, 2020
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (Actual): January 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Advanced Lung Cancer; 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; Metastatic Lung Cancer; KIF5B-RET; CCDC6-RET
• Additional Relevant MeSH Terms: Neoplasms, Glandular and Epithelial; Bronchial Neoplasms; Neoplasms; Lung Diseases; Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Head and Neck Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Respiratory Tract Diseases; Thoracic Neoplasms; Respiratory Tract Neoplasms; Neoplasms by Site; Neoplasms, Nerve Tissue; Bronchial Diseases; Carcinoma, Bronchogenic; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Pemetrexed; Gemcitabine; Carboplatin; Paclitaxel; Cisplatin; pembrolizumab; 130-nm albumin-bound paclitaxel; pralsetinib
• Other Study ID Numbers: BO42864; 2019-002463-10 (EudraCT Number); BLU-667-2303 (Registry Identifier: CT.Gov); 2023-505035-12-00 (Other Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No