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. Participants who have centrally confirmed progressive disease on the control arm have the option to crossover to pralsetinib.

Study Overview

• Status: Active, not recruiting
• 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): 221
• Phase: Phase 3

Expanded Access

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

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BO42864 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
    • Hospital Britanico; Oncologia
  • Ciudad Autonoma Buenos Aires, Argentina, C1426AGE
    • Centro Oncologico Korben; Oncology
  • La Rioja, Argentina, F5300COE
    • Centro Oncologico Riojano Integral (CORI)
• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital; Department of Medical Oncology
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
• Brazil
  • RN
    • Natal, RN, Brazil, 59040150
      • Liga Norte Riograndense Contra O Câncer
  • RS
    • Ijui, RS, Brazil, 98700-000
      • Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • SP
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
    • Sao Paulo, SP, Brazil, 01509-010
      • Hospital A. C. Camargo; Oncologia
• 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; Oncologie Medicale
  • Paris, France, 75970
    • Hopital Tenon;Pneumologie
  • Paris, France, 75018
    • Hopital Bichat Claude Bernard; Oncologie Serv.
  • Rennes, France, 35033
    • Hopital de Pontchaillou; Service de Pneumologie
  • Saint Herblain, France, 44805
    • Ico Rene Gauducheau; Oncologie
  • Strasbourg, France, 67091
    • CHU Strasbourg - Nouvel Hopital Civil
  • Toulouse cedex 9, France, 31100
    • CHU de Toulouse - Hôpital Larrey; Service de pneumologie et oncologie pneumologique
  • Villejuif, France, 94805
    • Institut Gustave Roussy; Departement Oncologie Medicale
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus, Medizinische Klinik I, Pneumologie MK1-A13
  • Gauting, Germany, 82131
    • Asklepios-Fachkliniken Muenchen-Gauting; Onkologie
  • Oldenburg, Germany, 26121
    • Pius-Hospital; Klinik fuer Haematologie und Onkologie
  • Schweinfurt, Germany, 97422
    • Leopoldina-Krankenhaus Medizinische Klinik II
  • Stuttgart, Germany, 70376
    • Klinik Schillerhöhe; Pneumologische Onkologie
• Ireland
  • Dublin, Ireland, D08 HNY1
    • St. James Hospital; Oncology
• Italy
  • Abruzzo
    • Chieti, Abruzzo, Italy, 66100
      • Ospedale Clinicizzato SS Annunziata
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
    • Napoli, Campania, Italy, 80131
      • Università degli Studi della Campania Luigi Vanvitelli
  • Emilia-Romagna
    • Ravenna, Emilia-Romagna, Italy, 48100
      • Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica
  • Lazio
    • Roma, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea
    • Roma, Lazio, Italy, 00184
      • AZ. Ospedaliera San Giovanni - Addolorata
    • Roma, Lazio, Italy, 00144
      • Istituto Nazionale Tumori Regina Elena
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • Istituto Europeo di Oncologia
    • Milano, Lombardia, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Milano, Lombardia, Italy, 20132
      • Irccs Ospedale San Raffaele
  • Puglia
    • Bari, Puglia, Italy, 70124
      • IRCCS Giovanni Paolo II Istituto Oncologico
  • Toscana
    • Pisa, Toscana, Italy, 56124
      • Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
    • Verona, Veneto, Italy, 37126
      • A.O.U. INTEGRATA DI VERONA-Ospedale Civile Maggiore Borgo Trento; U.O.C. Oncologia
• Japan
  • Aichi, Japan, 466-8560
    • Nagoya University Hospital
  • Aomori, Japan, 036-8563
    • Hirosaki University Hospital
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East
  • Ehime, Japan, 791-0295
    • Ehime University Hospital
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Fukuoka, Japan, 830-0011
    • Kurume University Hospital
  • Hokkaido, Japan, 003-0804
    • National Hospital Organization Hokkaido Cancer Center
  • Hyogo, Japan, 670-8520
    • National Hospital Organization Himeji Medical Center
  • Iwate, Japan, 028-3695
    • Iwate Medical University Hospital
  • Kanagawa, Japan, 241-8515
    • Kanagawa Cancer Center
  • Miyagi, Japan, 980-0873
    • Sendai Kousei Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Okayama, Japan, 710-8602
    • Kurashiki Central Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Osaka, Japan, 573-1191
    • Kansai Medical University Hospital
  • Saitama, Japan, 362-0806
    • Saitama Cancer Center
  • 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
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
• Mexico
  • Mexico CITY (federal District)
    • Cdmx, Mexico CITY (federal District), Mexico, 03100
      • Health Pharma Professional Research
  • SAN LUIS Potosi
    • San Luis Potosí, SAN LUIS Potosi, Mexico, 78209
      • Oncologico Potosino
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • NKI/AvL
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • 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
  • Warszawa, Poland, 02-781
    • Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers
• Portugal
  • Almada, Portugal, 2801-951
    • Hospital Garcia de Orta; Servico de Pneumologia
  • Braga, Portugal, 4710-243
    • Hospital de Braga; Serviço de Pneumologia
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
  • Vila Nova de Gaia, Portugal, 4434-502
    • Centro Hospitalar de Vila Nova de Gaia / Espinho E.P.E
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clínic. Barcelona
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28050
    • HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia; Servicio de oncologia
  • Zaragoza, Spain, 50009
    • Hosp Clinico Univ Lozano Blesa; División De Oncología Médica
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Univ. Central de Asturias; Servicio de Oncologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario Germans Trias i Pujol
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Insititut Catala D'Oncologia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
  • LA Coruña
    • A Coruña, LA Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruna
• Sweden
  • Stockholm, Sweden, 171 76
    • Karolinska Universitetssjukhuset, Solna; Kliniska prövningsenheten Z:4:01
• Switzerland
  • Zürich, Switzerland, 8091
    • UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
• Turkey
  • Adana, Turkey, 01060
    • Adana City Hospital, Medical Oncology
  • Adana, Turkey, 01120
    • Adana Baskent University Hospital; Medical Oncology
  • Ankara, Turkey, 06490
    • Ankara Bilkent City Hospital
  • Istanbul, Turkey, 34214
    • Medipol Mega Üniversite Hastanesi Göztepe
  • Kar?iyaka, Turkey, 35575
    • ?zmir Medical Point; Oncology
  • Seyhan, Turkey, 01140
    • Medical Park Seyhan Hospital; Oncology Department
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre; Oncology Dept
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary; Dept. of Medical Oncology
  • London, United Kingdom, SE1 9RT
    • Guys & St Thomas Hospital; Department of Oncology
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital; Dept of Med-Onc
  • London, United Kingdom, N7 9NH
    • University College Hospital; Department of Oncology
  • Manchester, United Kingdom, M2O 4BX
    • Christie Hospital Nhs Trust; Medical Oncology
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Dept of Medical Oncology
• United States
  • California
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
    • San Diego, California, United States, 92108
      • Southern California Kaiser Permanente
  • Texas
    • Houston, Texas, United States, 77090
      • Millennium Research & Clinical Development

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
Progression Free Survival (PFS)	Defined as the time from randomisation date to the first documented progressive disease (PD), as assessed by Blinded Independent Central Review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 central imaging review or death due to any cause, whichever occurs first.	Estimated at up to 32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as assessed by BICR according to RECIST 1.1 central imaging review.	Estimated at up to 32 months
Overall Survival (OS)	Defined as the time from randomisation date to death due to any cause.	Estimated at approximately 32 months
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	The intensity of Adverse Events (AEs) will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0).	Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)
Changes in Eastern Cooperative Oncology Group Performance Status (ECOG PS)	Further characterising safety and tolerability.	Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)
Duration of Response (DOR)	Defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as assessed by BICR according to RECIST v1.1.	Estimated at up to 32 months
Clinical Benefit Rate (CBR)	Defined as the proportion of participants who experience a best response of Stable Disease (SD) with a minimum duration of 6 months, a CR, or a PR, as assessed by BICR according to RECIST v1.1.	Estimated at up to 32 months
Disease Control Rate (DCR)	Defined as the proportion of participants who experience a best response of CR, or PR, or SD, as assessed by BICR according to RECIST v1.1.	Estimated at up to 32 months
European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-C30 Questionnaires	0-100 points (lower score represents worse quality of life)	From baseline until progressive disease or death (estimated 32 months)
European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-LC13 Scores	The item scale ranges from 1-4 (1 = Not at all; 4 = Very Much) where the EORTC-QLQ-LC13 scoring algorithm is applied to convert to a 0-100 point scale where 100 is best quality of life (QOL), for comparability.	From baseline until progressive disease or death (estimated 32 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 (Estimated): November 28, 2024
• Study Completion (Estimated): June 25, 2026

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 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

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; Neoplasms, Germ Cell and Embryonal; Head and Neck Neoplasms; Lung Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Respiratory Tract Diseases; Neoplasms by Site; Neoplasms by Histologic Type; Thoracic Neoplasms; Carcinoma, Bronchogenic; Respiratory Tract Neoplasms; Neoplasms, Nerve Tissue; Bronchial Diseases; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pembrolizumab; Albumin-Bound Paclitaxel; Pemetrexed; Pralsetinib; Gemcitabine
• Other Study ID Numbers: BO42864; 2019-002463-10 (EudraCT Number); BLU-667-2303 (Registry Identifier: CT.Gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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