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

• ClinicalTrials.gov Identifier: NCT04222972
• Recruitment Status: Recruiting
• First Posted: January 10, 2020
• Last Update Posted: February 2, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: January 3, 2020
• First Posted Date: January 10, 2020
• Last Update Posted Date: February 2, 2023
• Actual Study Start Date: July 24, 2020
• Estimated Primary Completion Date: November 28, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 26, 2021)

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.

Original Primary Outcome Measures (submitted: January 7, 2020)

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

Current Secondary Outcome Measures (submitted: May 26, 2021)

• 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.
• Overall Survival (OS) [ Time Frame: 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) [ 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).
• 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.
• 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.
• 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.
• 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.
• 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)
• 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.

Original Secondary Outcome Measures (submitted: January 7, 2020)

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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)
• 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)
• 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.
• 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)
• 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• Drug: Pralsetinib
  Administered orally
  Other Name: BLU-667
• 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

Study Arms

• Experimental: Pralsetinib
  Participants randomized to the Experimental Arm will receive Pralsetinib
  Intervention: Drug: Pralsetinib
• 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
  Interventions:

  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Pemetrexed
  • Drug: Pembrolizumab
  • Drug: Gemcitabine
  • Drug: Paclitaxel
  • Drug: Nab-Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 26, 2021): 226
• Original Estimated Enrollment (submitted: January 7, 2020): 250
• Estimated Study Completion Date: June 25, 2026
• Estimated Primary Completion Date: November 28, 2024 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: BO42864 https://forpatients.roche.com/; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, Costa Rica, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Norway, Panama, Poland, Portugal, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Hong Kong, Taiwan

Administrative Information

• NCT Number: NCT04222972
• Other Study ID Numbers: BO42864; 2019-002463-10 ( EudraCT Number ); BLU-667-2303 ( Registry Identifier: CT.Gov )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Blueprint Medicines Corporation
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Blueprint Medicines Corporation
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: February 2023