A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
- Conditions
- RET-fusion Non Small Cell Lung CancerLung NeoplasmCarcinoma, Non-Small-Cell LungRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseaseCarcinoma, Bronchogenic
- Interventions
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 223
Not provided
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
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
UZ Antwerpen
🇧🇪Edegem, Belgium
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital A. C. Camargo
🇧🇷Sao Paulo, São Paulo, Brazil
Clinica CIMCA
🇨🇷San Jose, Costa Rica
Institut Bergonie CLCC Bordeaux
🇫🇷Bordeaux, France
Hôpital Ambroise Paré - Boulogne-Billancourt
🇫🇷Boulogne Billancourt, France
CHRU Lille Service de Pneumologie et Oncologie Thoracique
🇫🇷Lille, France
Institut Paoli Calmettes
🇫🇷Marseille, France
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