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

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ClinicalTrials.gov Identifier: NCT04222972
Recruitment Status : Recruiting
First Posted : January 10, 2020
Last Update Posted : May 27, 2021
Sponsor:
Information provided by (Responsible Party):
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. Participants 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 Drug: Paclitaxel Drug: Nab-Paclitaxel 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 : 226 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 24, 2020
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pralsetinib
Participants randomized to the Experimental Arm will receive Pralsetinib
Drug: Pralsetinib
Administered orally
Other Name: 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: Carboplatin
Administered IV

Drug: Cisplatin
Administered IV

Drug: Pemetrexed
Administered IV

Drug: Pembrolizumab
Administered IV

Drug: Gemcitabine
Administered IV

Drug: Paclitaxel
Administered IV

Drug: Nab-Paclitaxel
Administered IV




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


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 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 BICR according to RECIST 1.1 central imaging review.

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

  3. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ 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 (NCI CTCAE v5.0).

  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 characterising safety and tolerability.

  5. Duration of Response (DOR) [ Time Frame: 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 BICR according to RECIST v1.1.

  6. Clinical Benefit Rate (CBR) [ Time Frame: 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 BICR according to RECIST v1.1.

  7. Disease Control Rate (DCR) [ Time Frame: 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 BICR according to RECIST v1.1.

  8. 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)

  9. 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.



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

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.

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: Reference Study ID Number: BO42864 http://www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
Show Show 93 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04222972    
Other Study ID Numbers: BO42864
2019-002463-10 ( EudraCT Number )
BLU-667-2303 ( Registry Identifier: CT.Gov )
First Posted: January 10, 2020    Key Record Dates
Last Update Posted: May 27, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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).

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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 Hoffmann-La Roche:
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
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic