AzTrials
AzTrials

RET-altered Non Small Cell Lung CancerPhase 1/2ARROWNCT03037385

Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

A Phase 1/2 study testing pralsetinib (BLU-667) in people with RET-altered Non Small Cell Lung Cancer and Medullary Thyroid Cancer, run by Hoffmann-La Roche at 71 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of pralsetinib (BLU-667) administered orally in participants with medullary thyroid cancer (MTC), RET-altered NSCLC and other… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pralsetinib (BLU-667)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
590 participants
Where
71 sitesin 13 countries
Study dates
17 Mar 2017to 21 Mar 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Diagnosis during dose escalation (Phase 1) - Pathologically documented, definitively diagnosed non-resectable advanced solid tumor.
  • All participants treated at doses > 120 mg per day must have MTC, or a RET-altered solid tumor per local assessment of tumor tissue and/or blood.
  • Diagnosis during dose expansion (Phase 2) - All participants (with the exception of participants with MTC enrolled in Groups 3, 4, and 9) must have an oncogenic RET-rearrangement/fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor, as determined by local or central testing of tumor or circulating tumor nucleic acid in blood; as detailed below.
  • Group 1 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion previously treated with a platinum-based chemotherapy.
  • Group 2 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion not previously treated with a platinum-based chemotherapy, including those who have not had any systemic therapy. Prior platinum chemotherapy in the neoadjuvant and adjuvant setting is permitted if the last dose of platinum was 4 months or more before the first dose of study drug.
  • Group 3 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit and was previously treated with cabozantinib and/or vandetanib.
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  • Group 4 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit and was not previously treated with cabozantinib and/or vandetanib.
  • Group 5 - participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion, have previously received standard of care (SOC) appropriate for their tumor type (unless there is no accepted standard therapy for the tumor type or the Investigator has determined that treatment with standard therapy is not appropriate), and must not have been eligible for any of the other groups.
  • Group 6 - participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion or mutation that was previously treated with a selective tyrosine kinase inhibitor (TKI) that inhibits RET
  • Group 7 - participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET mutation previously treated with SOC appropriate for the tumor type and not eligible for any of the other groups
  • Group 8 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion that was previously treated with a platinum based chemotherapy (China only).
  • Group 9 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit, and was not previously treated with systemic therapy (except prior cytotoxic chemotherapy is allowed) for advanced or metastatic disease (China only).
  • Participants must have non-resectable disease.
  • Dose expansion (Phase 2): Participants in all groups (except Group 7) must have measurable disease per RECIST v1.1 (or RANO, criteria if appropriate for tumor type).
  • Participants agrees to provide tumor tissue (archived, if available or a fresh biopsy) for RET status confirmation and is willing to consider an on-treatment tumor biopsy, if considered safe and medically feasible by the treating Investigator. For Phase 2, Group 6, participants are required to undergo a pretreatment biopsy to define baseline RET status in tumor tissue.
  • Participants has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.

Who cannot join

  • Participant's cancer has a known primary driver alteration other than RET. For example, NSCLC with a targetable mutation in EGFR, ALK, ROS1 or BRAF; colorectal with an oncogenic KRAS, NRAS, or BRAF mutation.
  • Participants had any of the following within 14 days prior to the first dose of study drug:
  • Platelet count < 75 × 10^9/L.
  • Absolute neutrophil count < 1.0 × 10^9/L.
  • Hemoglobin < 9.0 g/dL (red blood cell transfusion and erythropoietin may be used to reach at least 9.0 g/dL, but must have been administered at least 2 weeks prior to the first dose of study drug.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) if no hepatic metastases are present; > 5 × ULN if hepatic metastases are present.
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  • Total bilirubin > 1.5 × ULN; > 3 × ULN with direct bilirubin > 1.5 × ULN in presence of Gilbert's disease.
  • Estimated (Cockcroft-Gault formula) or measured creatinine clearance < 40 mL/min.
  • Total serum phosphorus > 5.5 mg/dL
  • QT interval corrected using Fridericia's formula (QTcF) > 470 msec or history of prolonged QT syndrome or Torsades de pointes, or familial history of prolonged QT syndrome.
  • Clinically significant, uncontrolled, cardiovascular disease.
  • Central nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms.
  • Clinically symptomatic interstitial lung disease or interstitial pneumonitis including radiation pneumonitis
  • Participants in Groups 1-5 and 7 (Phase 2) previously treated with a selective RET inhibitor
  • Participant had a major surgical procedure within 14 days of the first dose of study drug
  • Participant had a history of another primary malignancy that had been diagnosed or required therapy within the a year prior to the study
  • Pregnant or breastfeeding female participants

Trial locations and contacts

71 sites in 13 countries.

71 sites in 13 countries

United States18 sites

  • Albany Medical Center

    Albany, New York, 12208-3412

  • University of Michigan

    Ann Arbor, Michigan, 48109-0934

  • University of Colorado Anschutz Medical Campus

    Aurora, Colorado, 80045

  • Texas Oncology-Austin Midtown

    Austin, Texas, 78705-1165

  • Massachusetts General Hospital.

    Boston, Massachusetts, 02114-2696

  • Maryland Oncology Hematology, P.A.

    Columbia, Maryland, 21044-3257

  • Texas Oncology - Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030-4000

  • Mayo Clinic-Jacksonville

    Jacksonville, Florida, 32224

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136-1002

  • Weill Cornell Medical College-New York Presbyterian Hospital

    New York, New York, 10021

  • UC Irvine Medical Center

    Orange, California, 92868

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55902-3003

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University School of Medicine in St. Louis

    St Louis, Missouri, 63110-1010

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

China17 sites

  • Beijing Cancer Hospital

    Beijing, 100036

  • Beijing Cancer Hospital

    Beijing, 100142

  • The affiliated Cancer Hospital, School of Medicine, UESTC

    Chengdu, 610041

  • West China Hospital, Sichuan University

    Chengdu, 610041

  • Chongqing Cancer Hospital

    Chongqing, 400030

  • Fujian Provincial Cancer Hospital

    Fuzhou, 350014

  • First Affiliated Hospital of Gannan Medical University

    Ganzhou, 341000

  • Sun Yet-sen University Cancer Center

    Guangzhou, 510060

  • Guangdong General Hospital

    Guangzhou, 510080

  • Zhejiang Cancer Hospital

    Hangzhou, 310022

  • Jinan Central Hospital

    Jinan, 250013

  • Gansu Cancer Hospital

    Lanzhou, 730050

  • Fudan University Shanghai Cancer Center

    Shanghai, 200032

  • Fudan University Shanghai Cancer Center

    Shanghai, 200120

  • Tianjin Medical University Cancer Institute & Hospital

    Tianjing, 300060

  • Union Hospital Tongji Medical College Huazhong University of Science and Technology

    Wuhan, 430023

  • Henan Cancer Hospital

    Zhengzhou, 450008

Other trials in China

France8 sites

  • Institut Bergonie

    Bordeaux, 33000

  • Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez

    Lille, 59037

  • Centre Léon Bérard

    Lyon, 69008

  • Centre Antoine Lacassagne

    Nice, 6100

  • Institut Curie

    Paris, 75248

  • CHU de Rennes - Hopital de Pontchaillo

    Rennes, 35033

  • Hôpital Larrey

    Toulouse, 31059

  • Gustave Roussy

    Villejuif, 94800

Other trials in France

Germany5 sites

  • Helios Klinikum Emil von Behring GmbH

    Berlin, 14165

  • Universitätsklinikum Essen

    Essen, 45122

  • Thoraxklinik Heidelberg gGmbH

    Heidelberg, 69126

  • Klinikum der Universität München

    München, 81377

  • Pius-Hospital

    Oldenburg, 26121

Other trials in Germany

Spain5 sites

  • Vall d?Hebron Institute of Oncology (VHIO), Barcelona

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Institut Catala d Oncologia Hospitalet

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

Other trials in Spain

Italy4 sites

  • IEO

    Milan, Lombardy, 20141

  • Asst Grande Ospedale Metropolitano Niguarda

    Milan, Lombardy, 20162

  • Ospedale Santa Maria Delle Croci

    Ravenna, Emilia-Romagna, 48100

  • Istituto Nazionale Tumori Regina Elena

    Rome, Lazio, 00144

Other trials in Italy

South Korea4 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

  • Severance Hospital, Yonsei University Health System

    Seoul, 120-752

Other trials in South Korea

United Kingdom3 sites

  • Guys and St Thomas NHS Foundation Trust, Guys Hospital

    London, SE1 9RT

  • University College London Hospitals NHS Foundation Trust

    London, W1T 7HA

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

Other trials in United Kingdom

Netherlands2 sites

  • Antoni van Leeuwenhoek Ziekenhuis

    Amsterdam, 1066 CX

  • Universitair Medisch Centrum Groningen

    Groningen, 9713 GZ

Other trials in Netherlands

Taiwan2 sites

  • National Taiwan University Hospital

    Taipei, 10002

  • Taipei Veterans General Hospital

    Taipei, 11217

Other trials in Taiwan

Belgium1 site

  • Antwerp University Hospital

    Edegem, 2650

Other trials in Belgium

Hong Kong1 site

  • The Chinese University of Hong Kong

    Shatin, 123456

Other trials in Hong Kong

Singapore1 site

  • National Cancer Centre

    Singapore, 169610

Other trials in Singapore

About this study

Official title: A Phase 1/2 Study of the Highly-selective RET Inhibitor, BLU-667, in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors

This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of pralsetinib (BLU-667) administered orally in participants with medullary thyroid cancer (MTC), RET-altered NSCLC and other RET-altered solid tumors.

Read the detailed description

The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase 2). Both parts will enroll participants with advanced non-resectable NSCLC, advanced non-resectable thyroid cancer and other advanced solid tumors that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or the participants must be intolerant to or the Investigator has determined that treatment with standard therapy is not appropriate, or there must be no accepted standard therapy for their disease.

Being tested
pralsetinib (BLU-667)
Keywords
RET Lung, RET Thyroid, RET fusion, RET alteration, RET mutation, RET positive, RET inhibitor, RET altered, RET rearrangement, RET NSCLC, RET medullary thyroid cancer, RET-rearranged NSCLC, RET-rearranged thyroid, M918T, TRIM33-RET, RET fusion lung cancer, RET fusion thyroid cancer, lung cancer mutation, BLU 667, RET tyrosine kinase
Medical subject headings
Carcinoma, Medullary, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Thyroid Diseases, Thyroid Neoplasms, Thyroid Cancer, Papillary, Carcinoma, Neuroendocrine, Respiratory Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pralsetinib (BLU-667)Drug

    Also called BLU-667

    pralsetinib (BLU-667) is a potent and selective inhibitor of the RET mutations, fusions, and predicted resistant mutants

Study groups in NCT03037385
Study groupRoleWhat they receive
Phase 1 Dose EscalationExperimentalMultiple doses of pralsetinib (BLU-667) for oral administration.
Receives: Drug: pralsetinib (BLU-667)
Phase 2 Dose ExpansionExperimentalOral dose of pralsetinib (BLU-667) as determined during Dose Escalation.
Receives: Drug: pralsetinib (BLU-667)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib

    MTD was defined as the highest tolerated dose of pralsetinib without causing dose limiting toxicities (DLTs). DLT was defined as any Grade ≥3 adverse event (AE) occurring during Cycle 1 during Phase 1 (dose escalation) that is not clearly caused by something other than pralsetinib. RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase.

    Measured: Up to approximately 30.8 months

  2. Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs)

    An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. A 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 or birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.

    Measured: From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years)

  3. Phase 2: Overall Response Rate (ORR)

    ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) for at least two assessments with at least 28 days apart and no disease progression (PD) in between. Per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (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 SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), were presented.

    Measured: Up to approximately 79.8 months

Secondary outcomes (41)

  1. Phase 1: ORR

    ORR was defined as the percentage of participants with a confirmed CR or PR for at least two assessments with at least 28 days apart and no PD in between. Per RECIST v1.1, CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the 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 SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), was presented.

    Measured: Up to approximately 28 months

  2. Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status

    Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., Kinesin family member 5B (KIF5B), coiled-coil domain containing 6 (CCDC6), nuclear receptor coactivator 4 (NCOA4)). RET genotypes were determined by local testing and/or central analysis of circulating tumor deoxyribonucleic acid (ctDNA). ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.

    Measured: Up to approximately 79.8 months

  3. Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status

    Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.

    Measured: Up to approximately 79.8 months

  4. Phase 1 and Phase 2: ORR in RET-fusion Positive TC Participants With Specific RET Gene Status

    Oncogenic RET activation has been implicated as a driver in both MTC and differentiated TC (DTC). These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3.

    Measured: Up to approximately 79.8 months

  5. Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status

    Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or stable disease (SD) which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

    Measured: Up to approximately 79.8 months

  6. Phase 1 and Phase 2: CBR in RET-mutation MTC Participants With Specific RET Gene Status

    Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

    Measured: Up to approximately 79.8 months

  7. Phase 1 and Phase 2: CBR in RET-fusion Positive TC Participants With Specific RET Gene Status

    Oncogenic RET activation has been implicated as a driver in both MTC and DTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

    Measured: Up to approximately 79.8 months

  8. Phase 1 and Phase 2: Disease Control Rate (DCR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status

    Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

    Measured: Up to approximately 79.8 months

  9. Phase 1 and Phase 2: DCR in RET-mutation MTC Participants With Specific RET Gene Status

    Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

    Measured: Up to approximately 79.8 months

  10. Phase 1 and Phase 2: DCR in RET-fusion Positive TC Participants With Specific RET Gene Status

    Oncogenic RET activation has been implicated as a driver in both MTC and DTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DCR was assessed in participants having specific RET rearrangements. DCR was defined as the percentage of participants with a confirmed CR/PR, or SD. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline).

    Measured: Up to approximately 79.8 months

  11. Phase 1 and Phase 2: Duration of Response (DOR) in RET-mutation NSCLC Participants With Specific RET Gene Status

    Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5), CCDC6, NCOA4). RET genotypes were determined by local testing \&/or central analysis of circulating tumor deoxyribonucleic acid (ctDNA). DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR=disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to <10 mm. PR=at least a 30% decrease in SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study. DOR was analyzed using the Kaplan-Meier (KM) method.

    Measured: Up to approximately 79.8 months

  12. Phase 1 and Phase 2: DOR in RET-mutation MTC Participants With Specific RET Gene Status

    Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR= disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to <10 mm. PR=at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study (including baseline). DOR was analyzed using the Kaplan-Meier (KM) method.

    Measured: Up to approximately 79.8 months

  13. Phase 1 and Phase 2: DOR in RET-fusion Positive TC Participants With Specific RET Gene Status

    Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. DOR was assessed in participants having specific RET rearrangements. DOR=time from first documented CR/PR to date of first documented PD or death due to any cause, whichever occurs first. Per RECIST, CR= disappearance of all target lesions or any pathological lymph nodes (target or non-target) having a reduction in the short axis to <10 mm. PR=at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in absence of CR. PD=as at least a 20% increase in SOD of target lesions, taking as reference smallest SOD on study (including baseline). DOR was analyzed using the KM method.

    Measured: Up to approximately 79.8 months

  14. Phase 2: DOR

    DOR was defined as the time from first documented response (CR/PR) to the date of first documented PD or death due to any cause, whichever occurs first. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the 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 SOD of target lesions, taking as reference the smallest SOD on study (including baseline). DOR was analyzed using the KM methods.

    Measured: Up to approximately 79.8 months

  15. Phase 2: CBR

    CBR was defined as the percentage of participants with CR or PR, or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the 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. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). CBR and its two-sided 95% CI, which is based on the exact binomial distribution (Clopper-Pearson), were presented.

    Measured: Up to approximately 79.8 months

  16. Phase 2: DCR

    DCR was defined as the percentage of participants with a confirmed CR/PR, or SD, per RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the 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. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). DCR and its two-sided 95% CI, which is based on the exact binomial distribution (Clopper-Pearson), were presented.

    Measured: Up to approximately 79.8 months

  17. Phase 2: Progression-free Survival (PFS)

    PFS was defined as the time from the first dose of pralsetinib to the date of first documented PD or death due to any cause, whichever occurred first. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). PFS was analyzed using KM methods.

    Measured: Up to approximately 7 years

  18. Phase 2: Overall Survival (OS)

    OS was defined as the time from the first dose of pralsetinib to the date of death due to any causes.

    Measured: Up to approximately 7 years

  19. Phase 2: Intracranial ORR in RET-fusion Positive NSCLC Central Nervous System (CNS) Metastases Participants

    ORR=percentage of participants with CR or PR for at least 2 assessments with at least 28 days apart \& no PD in between. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/or cerebellum identified at baseline \& disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR =at least a 30% decrease in the SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline \& if in the absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or the identification of new CNS/brain lesion. PD=either at least 20% increase in the SOD of target CNS/brain lesion, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of any CNS/brain lesion identified as RECIST 1.1 nontarget lesions at baseline, or the identification of new CNS/brain lesion.

    Measured: Up to approximately 79.8 months

  20. Phase 2: Intracranial CBR in RET-fusion Positive NSCLC CNS Metastases Participants

    CBR=percentage of participants with CR/PR/SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in 1 cycle) from first dose date. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/ cerebellum identified at baseline\&disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR=at least a 30% decrease in SOD of any CNS/brain lesion, identified as target lesions at baseline \& if in absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or identification of new CNS/brain lesion. SD=neither sufficient shrinkage for PR nor sufficient increase for PD for target/non-target CNS/brain lesion, taking as reference smallest SOD while on study. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion.

    Measured: Up to approximately 79.8 months

  21. Phase 2: Intracranial DCR in RET-fusion Positive NSCLC CNS Metastases Participants

    DCR=percentage of participants with a confirmed CR/PR, or SD. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/or cerebellum identified at baseline \& disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR =at least a 30% decrease in the SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline \& if in the absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or the identification of new CNS/brain lesion. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target/non-target CNS/brain lesion, taking as reference the smallest SOD while on study. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion.

    Measured: Up to approximately 79.8 months

  22. Phase 2: Intracranial DOR in RET-fusion Positive NSCLC CNS Metastases Participants

    DOR=time from first documented CR/PR to the date of first documented PD/death due to any cause, whichever occurs first. CR=disappearance of all target CNS/brain lesion, including lesions in brain stem \&/ cerebellum identified at baseline \& disappearance of all non-target CNS/brain lesion at baseline \& no identification of new CNS/brain lesion. PR=at least a 30% decrease in SOD of any CNS/brain lesion, identified as RECIST 1.1 target lesions at baseline \& if in absence of unequivocal progression of any non-target CNS/brain lesion at baseline, or identification of new CNS/brain lesion. PD=either at least 20% increase in SOD of target CNS/brain lesion, taking as reference smallest sum on study. Unequivocal progression of any CNS/brain lesion nontarget lesions at baseline, or identification of new CNS/brain lesion. DOR was analyzed using the KM methods.

    Measured: Up to approximately 79.8 months

  23. Phase 1: Maximum Plasma Concentration (Cmax)

    Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  24. Phase 1: Time to Maximum Plasma Concentration (Tmax)

    Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  25. Phase 1: Time of Last Quantifiable Plasma Drug Concentration (Tlast)

    The maximum values for Tlast slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol. Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  26. Phase 1: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC0-24)

    Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: 24 hours postdose on Day 1 of Cycle 1 (1 cycle = 28 days)

  27. Phase 1: Plasma Drug Concentration at 24 Hours Postdose (C24hr)

    Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  28. Phase 1: Apparent Volume of Distribution (Vz/F)

    Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  29. Phase 1: Terminal Elimination Half-Life (t½)

    The maximum values for t1/2 slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol. Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  30. Phase 1: Apparent Oral Clearance (CL/F)

    Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  31. Phase 1: Accumulation Ratio for Cmax (RCmax)

    Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: 24 hours postdose on Day 15 of Cycle 1 (1 cycle = 28 days)

  32. Phase 1: Accumulation Ratio for AUC (RAUC)

    Number of participants in each arm of this OM is based on the actual treatment received. 1 participant originally assigned to the 200/100 mg arm received the 100/100 mg treatment and hence, was counted under the 100/100 mg arm for this OM.

    Measured: 24 hours postdose on Day 15 of Cycle 1 (1 cycle = 28 days)

  33. Phase 2: Cmax

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  34. Phase 2: Tmax

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  35. Phase 2: Tlast

    The maximum values for Tlast slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol.

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  36. Phase 2: AUC0-24

    Measured: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  37. Phase 2: C24hr

    Measured: 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  38. Phase 2: t½

    The maximum values for t1/2 slightly exceed 24 hours because the analysis used the actual time, i.e., the duration between dosing and actual sample collection, rather than the nominal sampling time of 24 hours specified in the protocol. The timeframe has been given as per nominal sampling timepoints pre-specified in the protocol.

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  39. Phase 2: CL/F

    Measured: Predose on 0.5, 1, 2, 4, 6, 8 and 24 hours postdose on Days 1 and 15 of Cycle 1 (1 cycle = 28 days)

  40. Phase 1: Percent Change From Baseline in Dual Specificity Phosphatase 6 (DUSP6)

    The dose dependent change in a mitogen-activated protein kinases (MAPK) pathway expression signature was analyzed for all available samples of MTC and NSCLC participants. Participants with archived sample (used as baseline) and on treatment Cycle 2 Day 1 (1 cycle = 28 days) tumor tissues with greater than 20% tumor cells are included in the analysis. The changes in tumor biomarker DUSP6 levels was explored.

    Measured: Baseline, Week 4

  41. Phase 1: Percent Change From Baseline in Sprout Receptor Tyrosine Kinase Signaling Antagonist 4 (SPRY4)

    The dose dependent change in a MAPK pathway expression signature was analyzed for all available samples of MTC and NSCLC participants. Participants with archived sample (used as baseline) and on treatment Cycle 2 Day 1 (1 cycle = 28 days) tumor tissues with greater than 20% tumor cells are included in the analysis. The changes in tumor biomarker SPRY4 levels was explored.

    Measured: Baseline, Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2017 (estimated)
  2. Study start17 Mar 2017
  3. Primary completion21 Mar 2024
  4. Study completion21 Mar 2024

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Phase 1 (Complete): * Advanced MTC, NSCLC or other solid tumor * 30-600mg (PO QD or BID) Phase 2 (400mg QD): * Group 1: RET fusion NSCLC previously treated with a platinum chemotherapy * Group 2: RET fusion NSCLC not previously treated for metastatic disease * Group 3: MTC previously treated with cabozantinib and/or vandetanib * Group 4: MTC not previously treated with cabozantinib or vandetanib * Group 5: Other solid tumors with a RET fusion not eligible for any of the other groups and previously treated with SOC or have no acceptable SOC for their tumor type as determined by the investigator * Group 6: Any solid tumor with a RET alteration (fusion or mutation) previously treated with a selective RET Inhibitor * Group 7: Other solid tumors with a RET mutation previously treated with SOC * Group 8: RET fusion NSCLC previously treated with a platinum chemotherapy (China only) * Group 9: MTC not previously treated with systemic therapy for advanced or metastatic disease (China only)
Masking
None (open label)
Enrolment
590 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03037385
Sponsor's protocol ID
BO42863
Other IDs
2016-004390-41, BLU-667-1101, 2016
Acronym
ARROW
Status last verified
May 2025
First submitted
20 Jan 2017
Last updated
31 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Besse B, Subbiah V, Curigliano G, Bowles DW, Doebele RC, Mansfield AS, Baik CS, de Lima Lopes G, Paz-Ares L, Taylor MH, Tan DSW, Alonso G, Gadgeel SM, Kalemkerian GP, Ou SI, van der Wekken AJ, Becerra CR, Evangelist M, Griesinger F, Liu SV, Lou Y, Mazieres J, Melear JM, Narang M, Saxena A, Thomas M, Wang S, Thomassen A, Lee DH, Kim DW, Gainor JF. Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced RET Fusion-Positive Non-Small Cell Lung Cancer. J Clin Oncol. 2026 May;44(13):1190-1197. doi: 10.1200/JCO-25-01489. Epub 2026 Mar 26.

    PubMed 41886723

  • Haddad RI, Bischoff L, Applewhite M, Bernet V, Blomain E, Brito M, Busaidy NL, Campbell M, DeLozier O, Duh QY, Ehya H, Grady E, Guo T, Haymart M, Hunt JP, Kandeel F, Kotwal A, Lamonica DM, Lorch J, Mandel SJ, Markovina S, Mydlarz W, Nabell L, Raeburn CD, Rezaee R, Ridge JA, Ritter H, Roth MY, Salgado SA, Scheri RP, Shah JP, Sipos JA, Sippel R, Sturgeon C, Wirth LJ, Wong RJ, Worden F, Yeh MW, Darlow S, Cassara CJ, Sliker B. NCCN Guidelines(R) Insights: Thyroid Carcinoma, Version 1.2025. J Natl Compr Canc Netw. 2025 Jul;23(7):e250033. doi: 10.6004/jnccn.2025.0033.

    PubMed 40639400

  • Subbiah V, Hu MI, Mansfield AS, Taylor MH, Schuler M, Zhu VW, Hadoux J, Curigliano G, Wirth L, Gainor JF, Alonso G, Adkins D, Godbert Y, Ahn MJ, Cassier PA, Cho BC, Lin CC, Zalutskaya A, Barata T, Trask P, Scalori A, Bordogna W, Heinzmann S, Brose MS. Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)-Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study. Thyroid. 2024 Jan;34(1):26-40. doi: 10.1089/thy.2023.0363.

    PubMed 38009200

  • Subbiah V, Burris HA 3rd, Kurzrock R. Revolutionizing cancer drug development: Harnessing the potential of basket trials. Cancer. 2024 Jan;130(2):186-200. doi: 10.1002/cncr.35085. Epub 2023 Nov 7.

    PubMed 37934000

  • Griesinger F, Curigliano G, Subbiah V, Baik CS, Tan DS, Lee DH, Misch D, Garralda E, Kim DW, van der Wekken AJ, Gainor JF, Paz-Ares L, Liu SV, Kalemkerian GP, Bowles DW, Mansfield AS, Lin JJ, Smoljanovic V, Rahman A, Zalutskaya A, Louie-Gao M, Boral AL, Mazieres J. Pralsetinib in patients with RET fusion-positive non-small-cell lung cancer: A plain language summary of the ARROW study. Future Oncol. 2024 Feb;20(6):297-306. doi: 10.2217/fon-2023-0155. Epub 2023 Nov 2.

    PubMed 37916501

  • Zhou Q, Zhao J, Chang J, Wang H, Fan Y, Wang K, Wu G, Nian W, Sun Y, Sun M, Wang X, Shi H, Zheng X, Yao S, Qin M, Shen Z, Yang J, Wu YL. Efficacy and safety of pralsetinib in patients with advanced RET fusion-positive non-small cell lung cancer. Cancer. 2023 Oct 15;129(20):3239-3251. doi: 10.1002/cncr.34897. Epub 2023 Jun 6.

    PubMed 37282666

  • Subbiah V, Cassier PA, Siena S, Garralda E, Paz-Ares L, Garrido P, Nadal E, Vuky J, Lopes G, Kalemkerian GP, Bowles DW, Seetharam M, Chang J, Zhang H, Green J, Zalutskaya A, Schuler M, Fan Y, Curigliano G. Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nat Med. 2022 Aug;28(8):1640-1645. doi: 10.1038/s41591-022-01931-y. Epub 2022 Aug 12.

    PubMed 35962206

  • Popat S, Liu SV, Scheuer N, Hsu GG, Lockhart A, Ramagopalan SV, Griesinger F, Subbiah V. Addressing challenges with real-world synthetic control arms to demonstrate the comparative effectiveness of Pralsetinib in non-small cell lung cancer. Nat Commun. 2022 Jun 17;13(1):3500. doi: 10.1038/s41467-022-30908-1.

    PubMed 35715405

  • Subbiah V, Hu MI, Wirth LJ, Schuler M, Mansfield AS, Curigliano G, Brose MS, Zhu VW, Leboulleux S, Bowles DW, Baik CS, Adkins D, Keam B, Matos I, Garralda E, Gainor JF, Lopes G, Lin CC, Godbert Y, Sarker D, Miller SG, Clifford C, Zhang H, Turner CD, Taylor MH. Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study. Lancet Diabetes Endocrinol. 2021 Aug;9(8):491-501. doi: 10.1016/S2213-8587(21)00120-0. Epub 2021 Jun 9.

    PubMed 34118198

  • Gainor JF, Curigliano G, Kim DW, Lee DH, Besse B, Baik CS, Doebele RC, Cassier PA, Lopes G, Tan DSW, Garralda E, Paz-Ares LG, Cho BC, Gadgeel SM, Thomas M, Liu SV, Taylor MH, Mansfield AS, Zhu VW, Clifford C, Zhang H, Palmer M, Green J, Turner CD, Subbiah V. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol. 2021 Jul;22(7):959-969. doi: 10.1016/S1470-2045(21)00247-3. Epub 2021 Jun 9.

    PubMed 34118197

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing pralsetinib (BLU-667) in people with RET-altered Non Small Cell Lung Cancer and Medullary Thyroid Cancer, run by Hoffmann-La Roche at 71 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 71 sites in United States, China, France, Germany, Spain and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib (time frame: Up to approximately 30.8 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03037385, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2025.

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