Clinical Trials /

AcceleRET Lung Study of Pralsetinib for 1L RET Fusion-positive, Metastatic NSCLC

NCT04222972

Description:

This is an international, randomized, open-label, Phase 3 study designed to evaluate whether the potent and selective RET inhibitor, pralsetinib, improves outcome 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 patients with RET fusion-positive metastatic NSCLC who have not previously received systemic anticancer therapy for metastatic disease. Patients who have centrally confirmed progressive disease on the control arm have the option to crossover to pralsetinib.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: AcceleRET Lung Study of Pralsetinib for 1L RET Fusion-positive, Metastatic NSCLC
  • Official Title: A Randomized, Open-Label, Phase 3 Study of Pralsetinib Versus Standard of Care for First Line Treatment of RET Fusion-positive, Metastatic Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: BLU-667-2303
  • NCT ID: NCT04222972

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
  • Bronchial Diseases
  • Head and Neck Neoplasms
  • Adenocarcinoma
  • Carcinoma
  • Neoplasms by Histologic Type
  • Neoplasms, Germ Cell and Embryonal
  • Neoplasms, Nerve Tissue

Interventions

DrugSynonymsArms
PralsetinibBLU-667Pralsetinib
CarboplatinPlatinum doublet with or without pembrolizumab
CisplatinPlatinum doublet with or without pembrolizumab
PemetrexedPlatinum doublet with or without pembrolizumab
PembrolizumabPlatinum doublet with or without pembrolizumab
GemcitabinePlatinum doublet with or without pembrolizumab

Purpose

This is an international, randomized, open-label, Phase 3 study designed to evaluate whether the potent and selective RET inhibitor, pralsetinib, improves outcome 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 patients with RET fusion-positive metastatic NSCLC who have not previously received systemic anticancer therapy for metastatic disease. Patients who have centrally confirmed progressive disease on the control arm have the option to crossover to pralsetinib.

Trial Arms

NameTypeDescriptionInterventions
PralsetinibExperimentalPatients randomized to the Experimental Arm will receive pralsetinib
  • Pralsetinib
Platinum doublet with or without pembrolizumabActive ComparatorPatients 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
  • Cisplatin
  • Pemetrexed
  • Pembrolizumab
  • Gemcitabine

Eligibility Criteria

        Main inclusion criteria:

          -  Patient is ≥18 years of age

          -  Patient has pathologically confirmed, definitively diagnosed, 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.

          -  Patient must have a documented RET-fusion

          -  Patient has measurable disease based on RECIST 1.1 as determined by the local site
             Investigator/radiology assessment.

          -  Patient has an ECOG PS of 0-1.

          -  Patient should not have received any prior anticancer therapy for metastatic disease.

               -  Patients 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.

               -  Patients that received previous immune checkpoint inhibitors in the adjuvant or
                  consolidation following chemoradiation are not allowed to receive pembrolizumab
                  if randomized in Arm B

          -  Patient is an appropriate candidate for and agrees to receive 1 of the Investigator
             choice platinum-based chemotherapy regimens if randomized to Arm B.

          -  Patient provides signed informed consent to participate in the study.

        Main exclusion criteria:

          -  Patient'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.

          -  Patient previously received treatment with a selective RET inhibitor.

          -  Patient 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.

          -  Patient has a presence of Grade 2 or worse interstitial lung disease or interstitial
             pneumonitis, including radiation pneumonitis within 28 days before randomization.

          -  Patient 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 patient requires corticosteroids for management of CNS disease, the
             dose must have been stable for the 2 weeks before Cycle 1 Day 1.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Estimated at up to 32 months
Safety Issue:
Description:Defined as the number of weeks from randomization date to the earlier of documented progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 central imaging review or death due to any cause

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Estimated at up to 32 months
Safety Issue:
Description:Defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST 1.1 central imaging review
Measure:Overall Survival (OS)
Time Frame:Estimated at approximately 32 months
Safety Issue:
Description:Defined as the number of weeks from randomization date to death due to any cause
Measure:Number of patients with adverse events and serious adverse events
Time Frame:Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)
Safety Issue:
Description:The intensity of adverse events (AEs) will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0
Measure:Changes in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Time Frame:Baseline, at every 21 day cycle visit until progressive disease or death (estimated 32 months)
Safety Issue:
Description:Further characterizing safety and tolerability
Measure:Duration of Response (DOR)
Time Frame:Estimated at up to 32 months
Safety Issue:
Description:Defined as the number of weeks from the time criteria are first met for either CR or PR, until the first date that PD is objectively documented or death due to PD
Measure:Clinical Benefit Rate (CBR)
Time Frame:Estimated at up to 32 months
Safety Issue:
Description:Defined as the proportion of patients who experience a best response of stable disease (SD) with a minimum duration of 16 weeks, a CR, or a PR according to RECIST 1.1
Measure:Disease Control Rate (DCR)
Time Frame:Estimated at up to 32 months
Safety Issue:
Description:Defined as the proportion of patients who experience a best response of CR, or PR, or SD according to RECIST 1.1
Measure:Time to intracranial progression in accordance with RECIST 1.1 criteria
Time Frame:Estimated at up to 32 months
Safety Issue:
Description:Assessing Central Nervous System (CNS) activity as measured by time to intracranial progression for all patients
Measure:Intracranial response rate in accordance with RECIST 1.1 criteria
Time Frame:Estimated at up to 32 months
Safety Issue:
Description:Assessing CNS activity as measured by intracranial response rate (for patients with measurable intracranial metastases at screening)
Measure:European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-C30 Questionnaires
Time Frame:From baseline until progressive disease or death (estimated 32 months)
Safety Issue:
Description:0-100 points (lower score represents worse quality of life)
Measure:European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-LC13 Scores
Time Frame:From baseline until progressive disease or death (estimated 32 months)
Safety Issue:
Description: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.
Measure:EuroQoL 5 Dimension (EQ-5D-5L) Assessment
Time Frame:From baseline until progressive disease or death (estimated 32 months)
Safety Issue:
Description:0-100 points (higher value represents better symptom outcomes)
Measure:Plasma drug concentration at specified time points of pralsetinib
Time Frame:Assessed every 3 weeks, up to 9 weeks from baseline
Safety Issue:
Description:Assessing drug exposure parameters

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Blueprint Medicines Corporation

Trial Keywords

  • Advanced Non-Small Cell Lung Cancer
  • RET Lung
  • RET Mutation
  • RET Alteration
  • RET Positive
  • RET Inhibitor
  • RET Altered
  • RET Rearrangement
  • RET NSCLC
  • RET-Rearranged NSCLC
  • RET Fusion
  • RET Fusion Lung Cancer
  • M918T
  • TRIM33-RET
  • Lung Cancer Mutation
  • BLU 667
  • Pralsetinib
  • RET Tyrosine Kinase
  • RET Gene Mutation
  • RET Kinase
  • Advanced Lung Cancer
  • Metastatic Lung Cancer
  • KIF5B-RET
  • CCDC6-RET

Last Updated

February 14, 2020