RET-fusion Non Small Cell Lung CancerPhase 3AcceleRET-LungNCT04222972
A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
A Phase 3 study testing Pralsetinib, Carboplatin and Cisplatin in people with RET-fusion Non Small Cell Lung Cancer and Lung Neoplasm, run by Hoffmann-La Roche at 74 sites in 22 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- RET-fusion Non Small Cell Lung Cancer, Lung Neoplasm, Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Pralsetinib, Carboplatin and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 223 participants
- Where
- 74 sitesin 22 countries
- Study dates
- 24 Jul 2020to 27 Jan 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
74 sites in 22 countries.
74 sites in 22 countries
France12 sites
Institut Bergonie CLCC Bordeaux
Bordeaux, 33000
Hôpital Ambroise Paré - Boulogne-Billancourt
Boulogne-Billancourt, 92100
Hôpital Louis Pradel, Hospices Civils de Lyon
Bron, 69677
CHRU Lille Service de Pneumologie et Oncologie Thoracique
Lille, 59000
Institut Paoli Calmettes
Marseille, 13273
Hopital Bichat Claude Bernard
Paris, 75018
Hopital Tenon
Paris, 75970
Hopital de Pontchaillou
Rennes, 35033
Ico Rene Gauducheau
Saint-Herblain, 44805
CHU Strasbourg - Nouvel Hopital Civil
Strasbourg, 67091
CHU de Toulouse - Hôpital Larrey
Toulouse, 31100
Institut Gustave Roussy
Villejuif, 94805
Italy12 sites
IRCCS Giovanni Paolo II Istituto Oncologico
Bari, Apulia, 70124
Ospedale Clinicizzato SS Annunziata
Chieti, Abruzzo, 66100
Irccs Ospedale San Raffaele
Milan, Lombardy, 20132
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, 20133
Istituto Europeo Di Oncologia
Milan, Lombardy, 20141
Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
Naples, Campania, 80131
IOV - Istituto Oncologico Veneto - IRCCS
Padova, Veneto, 35128
Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello
Pisa, Tuscany, 56124
Ospedale Provinciale Santa Maria Delle Croci
Ravenna, Emilia-Romagna, 48100
Istituto Nazionale Tumori Regina Elena
Rome, Lazio, 00144
AZ. Ospedaliera San Giovanni - Addolorata
Rome, Lazio, 00184
A.O.U. INTEGRATA DI VERONA-Ospedale Civile Maggiore Borgo Trento
Verona, Veneto, 37126
Spain9 sites
Complejo Hospitalario Universitario A Coruña
A Coruña, LA Coruna, 15006
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Insititut Catala D'Oncologia
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Hospital Ramon y Cajal
Madrid, 28034
Hospital de Madrid Norte Sanchinarro- Centro Integral Oncologico Clara Campal
Madrid, 28050
Hospital Regional Universitario de Malaga
Málaga, 29010
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008
Hosp Clinico Univ Lozano Blesa
Zaragoza, 50009
Japan7 sites
Kyushu University Hospital
Fukuoka, 812-8582
National Hospital Organization Himeji Medical Center
Hyōgo, 670-8520
Osaka International Cancer Institute
Osaka, 541-8567
Kansai Medical University Hospital
Osaka, 573-1191
Juntendo University Hospital
Tokyo, 113-8431
The Cancer Institute Hospital of JFCR
Tokyo, 135-8550
National Hospital Organization Yamaguchi - Ube Medical Center
Yamaguchi, 755-0241
Germany5 sites
Universitätsklinikum Carl Gustav Carus, Medizinische Klinik I, Pneumologie MK1-A13
Dresden, 01307
Asklepios-Fachkliniken Muenchen-Gauting
Gauting, 82131
Pius-Hospital
Oldenburg, 26121
Leopoldina-Krankenhaus Medizinische Klinik II
Schweinfurt, 97422
Klinik Schillerhöhe
Stuttgart, 70376
United Kingdom5 sites
Velindre Cancer Centre
Cardiff, CF14 2TL
Leicester Royal Infirmary
Leicester, LE1 5WW
Guys & St Thomas Hospital
London, SE1 9RT
Royal Marsden Hospital
London, SW3 6JJ
Christie Hospital Nhs Trust
Manchester, M2O 4BX
South Korea4 sites
National Cancer Center
Goyang-si, 10408
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Turkey (Türkiye)3 sites
Adana City Hospital, Medical Oncology
Adana, 01060
Ankara Bilkent City Hospital
Ankara, 06490
?zmir Medical Point
Kar?iyaka, 35575
Argentina2 sites
Hospital Britanico
Buenos Aires, C1280AEB
Centro Oncologico Riojano Integral (CORI)
La Rioja, F5300COE
Brazil2 sites
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Hospital A. C. Camargo
São Paulo, São Paulo, 01509-010
Netherlands2 sites
NKI/AvL
Amsterdam, 1066 CX
Maastricht University Medical Center
Maastricht, 6229 HX
Australia1 site
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Mexico1 site
Health Pharma Professional Research
Mexico City, Mexico CITY (federal District), 03100
Poland1 site
Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
Warsaw, 02-781
About this study
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
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
- Being tested
- Pralsetinib, Carboplatin, Cisplatin, Pemetrexed, Pembrolizumab
- 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
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Diseases, Respiratory Tract Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PralsetinibDrug
Also called BLU-667
Administered orally
CarboplatinDrug
Administered IV
CisplatinDrug
Administered IV
PemetrexedDrug
Administered IV
PembrolizumabDrug
Administered IV
GemcitabineDrug
Administered IV
PaclitaxelDrug
Administered IV
Nab-PaclitaxelDrug
Administered IV
| Study group | Role | What they receive |
|---|---|---|
| Pralsetinib | Experimental | Participants randomized to the Experimental Arm will receive Pralsetinib Receives: Drug: Pralsetinib |
| Platinum-based chemotherapy with or without pembrolizumab | Active comparator | 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 Receives: Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Nab-Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to approximately 50 months
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 50 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2020
- Study start24 Jul 2020
- Primary completion27 Jan 2025
- Study completion27 Jan 2025
Why it stopped: Early termination of the study resulted from organizational and commercial decisions that led to the discontinuation of pralsetinib's global marketing and development in all territories (excluding US and Greater China).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for RET-fusion Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 223 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04222972
- Sponsor's protocol ID
- BO42864
- Other IDs
- 2019-002463-10, BLU-667-2303, 2023-505035-12-00, 2023, 2019
- Acronym
- AcceleRET-Lung
- Status last verified
- Feb 2026
- First submitted
- 3 Jan 2020
- Last updated
- 5 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
- Expanded access
- Available