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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04222972
Recruitment Status : Recruiting
First Posted : January 10, 2020
Last Update Posted : October 30, 2020
Sponsor:
Information provided by (Responsible Party):
Blueprint Medicines Corporation

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Drug: Pralsetinib Drug: Carboplatin Drug: Cisplatin Drug: Pemetrexed Drug: Pembrolizumab Drug: Gemcitabine Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 24, 2020
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pralsetinib
Patients randomized to the Experimental Arm will receive pralsetinib
Drug: Pralsetinib
Administered orally
Other Name: BLU-667

Active Comparator: Platinum doublet with or without pembrolizumab

Patients 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

Drug: Carboplatin
Administered IV

Drug: Cisplatin
Administered IV

Drug: Pemetrexed
Administered IV

Drug: Pembrolizumab
Administered IV

Drug: Gemcitabine
Administered IV




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Estimated at up to 32 months ]
    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 :
  1. Overall Response Rate (ORR) [ Time Frame: Estimated at up to 32 months ]
    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

  2. Overall Survival (OS) [ Time Frame: Estimated at approximately 32 months ]
    Defined as the number of weeks from randomization date to death due to any cause

  3. 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) ]
    The intensity of adverse events (AEs) will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0

  4. 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) ]
    Further characterizing safety and tolerability

  5. Duration of Response (DOR) [ Time Frame: Estimated at up to 32 months ]
    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

  6. Clinical Benefit Rate (CBR) [ Time Frame: Estimated at up to 32 months ]
    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

  7. Disease Control Rate (DCR) [ Time Frame: Estimated at up to 32 months ]
    Defined as the proportion of patients who experience a best response of CR, or PR, or SD according to RECIST 1.1

  8. Time to intracranial progression in accordance with RECIST 1.1 criteria [ Time Frame: Estimated at up to 32 months ]
    Assessing Central Nervous System (CNS) activity as measured by time to intracranial progression for all patients

  9. Intracranial response rate in accordance with RECIST 1.1 criteria [ Time Frame: Estimated at up to 32 months ]
    Assessing CNS activity as measured by intracranial response rate (for patients with measurable intracranial metastases at screening)

  10. 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) ]
    0-100 points (lower score represents worse quality of life)

  11. 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) ]
    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.

  12. EuroQoL 5 Dimension (EQ-5D-5L) Assessment [ Time Frame: From baseline until progressive disease or death (estimated 32 months) ]
    0-100 points (higher value represents better symptom outcomes)

  13. Plasma drug concentration at specified time points of pralsetinib [ Time Frame: Assessed every 3 weeks, up to 9 weeks from baseline ]
    Assessing drug exposure parameters



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04222972


Contacts
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Contact: Blueprint Medicines 617-714-6707 medinfo@blueprintmedicines.com

Locations
Show Show 58 study locations
Sponsors and Collaborators
Blueprint Medicines Corporation
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Responsible Party: Blueprint Medicines Corporation
ClinicalTrials.gov Identifier: NCT04222972    
Other Study ID Numbers: BLU-667-2303
First Posted: January 10, 2020    Key Record Dates
Last Update Posted: October 30, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Blueprint Medicines Corporation:
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
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Neoplasms
Carcinoma, Non-Small-Cell Lung
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Thoracic Neoplasms
Respiratory Tract Neoplasms
Carcinoma, Bronchogenic
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Lung Diseases
Respiratory Tract Diseases
Bronchial Diseases
Neoplasms, Glandular and Epithelial
Bronchial Neoplasms
Gemcitabine
Carboplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors