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

Phase 3

Completed

• Conditions: RET-fusion Non Small Cell Lung Cancer; Lung Neoplasm; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Disease; Carcinoma, Bronchogenic
• Interventions: Drug: Pralsetinib; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Nab-Paclitaxel

• Registration Number: NCT04222972
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This is an international, randomized, open-label, Phase 3 study designed to evaluate whether the potent and selective RET inhibitor, pralsetinib, improves outcomes when compared to a platinum chemotherapy-based regimen chosen by the Investigator from a list of standard of care treatments, as measured primarily by progression free survival (PFS), for participants with RET fusion-positive metastatic NSCLC who have not previously received systemic anticancer therapy for metastatic disease.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-03
• Study First Submitted QC: 2020-01-07
• Study First Posted: 2020-01-10
• Study Start: 2020-07-24
• Primary Completion: 2025-01-27
• Study Completion: 2025-01-27
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-05
• Last Update Posted: 2025-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 223

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pralsetinib	Pralsetinib	Participants randomized to the Experimental Arm will receive Pralsetinib
Platinum-based chemotherapy with or without pembrolizumab	Cisplatin	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
Platinum-based chemotherapy with or without pembrolizumab	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
Platinum-based chemotherapy with or without pembrolizumab	Paclitaxel	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
Platinum-based chemotherapy with or without pembrolizumab	Nab-Paclitaxel	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
Platinum-based chemotherapy with or without pembrolizumab	Carboplatin	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
Platinum-based chemotherapy with or without pembrolizumab	Pemetrexed	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
Platinum-based chemotherapy with or without pembrolizumab	Gemcitabine	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

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Estimated at up to 32 months	Defined as the time from randomisation date to the first documented progressive disease (PD), as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Estimated at up to 32 months	Defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as assessed by investigator according to RECIST 1.1.
Overall Survival (OS)	Estimated at approximately 32 months	Defined as the time from randomisation date to death due to any cause.
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)	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).
Changes in Eastern Cooperative Oncology Group Performance Status (ECOG PS)	Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)	Further characterising safety and tolerability.
Duration of Response (DOR)	Estimated at up to 32 months	Defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as assessed by investigator according to RECIST v1.1.
Clinical Benefit Rate (CBR)	Estimated at up to 32 months	Defined as the proportion of participants who experience a best response of Stable Disease (SD) with a minimum duration of 6 months, a CR, or a PR, as assessed by investigator according to RECIST v1.1.
Disease Control Rate (DCR)	Estimated at up to 32 months	Defined as the proportion of participants who experience a best response of CR, or PR, or SD, as assessed by investigator according to RECIST v1.1.

Trial Locations

Locations (67)

Hospital Britanico; 🇦🇷 Buenos Aires, Argentina

Hôpital Ambroise Paré - Boulogne-Billancourt; 🇫🇷 Boulogne Billancourt, France

CHRU Lille Service de Pneumologie et Oncologie Thoracique; 🇫🇷 Lille, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

Hopital Bichat Claude Bernard; 🇫🇷 Paris, France

Hopital Tenon; 🇫🇷 Paris, France

Hopital de Pontchaillou; 🇫🇷 Rennes, France

CHU Strasbourg - Nouvel Hopital Civil; 🇫🇷 Strasbourg, France

CHU de Toulouse - Hôpital Larrey; 🇫🇷 Toulouse cedex 9, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Universitätsklinikum Carl Gustav Carus, Medizinische Klinik I, Pneumologie MK1-A13; 🇩🇪 Dresden, Germany

Royal North Shore Hospital; 🇦🇺 St Leonards, New South Wales, Australia

UZ Antwerpen; 🇧🇪 Edegem, Belgium

St. James Hospital; 🇮🇪 Dublin, Ireland

National Hospital Organization Himeji Medical Center; 🇯🇵 Hyogo, Japan

NKI/AvL; 🇳🇱 Amsterdam, Netherlands

Hospital Regional Universitario de Malaga; 🇪🇸 Malaga, Spain

Hosp Clinico Univ Lozano Blesa; 🇪🇸 Zaragoza, Spain

Karolinska Universitetssjukhuset, Solna; 🇸🇪 Stockholm, Sweden

Institut Bergonie CLCC Bordeaux; 🇫🇷 Bordeaux, France

Hospital A. C. Camargo; 🇧🇷 Sao Paulo, São Paulo, Brazil

Clinica CIMCA; 🇨🇷 San Jose, Costa Rica

Hospital Sao Lucas - PUCRS; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Asklepios-Fachkliniken Muenchen-Gauting; 🇩🇪 Gauting, Germany

Pius-Hospital; 🇩🇪 Oldenburg, Germany

Leopoldina-Krankenhaus Medizinische Klinik II; 🇩🇪 Schweinfurt, Germany

Klinik Schillerhöhe; 🇩🇪 Stuttgart, Germany

Ospedale Clinicizzato SS Annunziata; 🇮🇹 Chieti, Abruzzo, Italy

Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale; 🇮🇹 Napoli, Campania, Italy

Ospedale Provinciale Santa Maria Delle Croci; 🇮🇹 Ravenna, Emilia-Romagna, Italy

Istituto Nazionale Tumori Regina Elena; 🇮🇹 Roma, Lazio, Italy

AZ. Ospedaliera San Giovanni - Addolorata; 🇮🇹 Roma, Lazio, Italy

Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; 🇮🇹 Pisa, Toscana, Italy

IOV - Istituto Oncologico Veneto - IRCCS; 🇮🇹 Padova, Veneto, Italy

A.O.U. INTEGRATA DI VERONA-Ospedale Civile Maggiore Borgo Trento; 🇮🇹 Verona, Veneto, Italy

Kyushu University Hospital; 🇯🇵 Fukuoka, Japan

Osaka International Cancer Institute; 🇯🇵 Osaka, Japan

Kansai Medical University Hospital; 🇯🇵 Osaka, Japan

Juntendo University Hospital; 🇯🇵 Tokyo, Japan

The Cancer Institute Hospital of JFCR; 🇯🇵 Tokyo, Japan

National Hospital Organization Yamaguchi - Ube Medical Center; 🇯🇵 Yamaguchi, Japan

National Cancer Center; 🇰🇷 Goyang-si, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Health Pharma Professional Research; 🇲🇽 Cdmx, Mexico CITY (federal District), Mexico

Maastricht University Medical Center; 🇳🇱 Maastricht, Netherlands

Hemato Oncología de Panamá Especializada; 🇵🇦 Panama City, Panama

Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; 🇵🇱 Warszawa, Poland

IPO do Porto; 🇵🇹 Porto, Portugal

Insititut Catala D'Oncologia; 🇪🇸 Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Complejo Hospitalario Universitario A Coruña; 🇪🇸 A Coruña, LA Coruna, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Marañon; 🇪🇸 Madrid, Spain

Hospital Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital de Madrid Norte Sanchinarro- Centro Integral Oncologico Clara Campal; 🇪🇸 Madrid, Spain

UniversitätsSpital Zürich; 🇨🇭 Zürich, Switzerland

Adana City Hospital, Medical Oncology; 🇹🇷 Adana, Turkey

Ankara Bilkent City Hospital; 🇹🇷 Ankara, Turkey

?zmir Medical Point; 🇹🇷 Kar?iyaka, Turkey

Velindre Cancer Centre; 🇬🇧 Cardiff, United Kingdom

Leicester Royal Infirmary; 🇬🇧 Leicester, United Kingdom

University College Hospital; 🇬🇧 London, United Kingdom

Guys & St Thomas Hospital; 🇬🇧 London, United Kingdom

Royal Marsden Hospital; 🇬🇧 Sutton, United Kingdom

Christie Hospital Nhs Trust; 🇬🇧 Manchester, United Kingdom