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

• ClinicalTrials.gov Identifier: NCT04222972
• Recruitment Status: Recruiting
• First Posted: January 10, 2020
• Last Update Posted: October 30, 2020
• Sponsor: Blueprint Medicines Corporation
• Information provided by (Responsible Party): Blueprint Medicines Corporation

Tracking Information

• First Submitted Date: January 3, 2020
• First Posted Date: January 10, 2020
• Last Update Posted Date: October 30, 2020
• Actual Study Start Date: July 24, 2020
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

Current 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

• Original Primary Outcome Measures: Same as current

Current 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• 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

Study Arms

• Experimental: Pralsetinib
  Patients randomized to the Experimental Arm will receive pralsetinib
  Intervention: Drug: Pralsetinib
• 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

  Interventions:

  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Pemetrexed
  • Drug: Pembrolizumab
  • Drug: Gemcitabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 7, 2020): 250
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

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

• Listed Location Countries: Belgium, Finland, France, Germany, Hong Kong, Italy, Korea, Republic of, Netherlands, Norway, Poland, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04222972
• Other Study ID Numbers: BLU-667-2303
• 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: Not Provided
• Responsible Party: Blueprint Medicines Corporation
• Study Sponsor: Blueprint Medicines Corporation
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Blueprint Medicines Corporation
• Verification Date: October 2020