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: February 18, 2020
• Sponsor: Blueprint Medicines Corporation
• Information provided by (Responsible Party): Blueprint Medicines Corporation

Study Description

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 ...

Study Design

• 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
• Estimated Study Start Date: February 14, 2020
• Estimated Primary Completion Date: September 2023
• Estimated Study Completion Date: December 2024

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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.

Contacts and Locations

Contacts

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

Locations

United States, Texas

Millennium Oncology; Recruiting

Houston, Texas, United States, 77090

Sponsors and Collaborators

Blueprint Medicines Corporation

More Information

• Responsible Party: Blueprint Medicines Corporation
• ClinicalTrials.gov Identifier: NCT04222972
• Other Study ID Numbers: BLU-667-2303
• First Posted: January 10, 2020
• Last Update Posted: February 18, 2020
• Last Verified: February 2020

• 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:

Carcinoma; Lung 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; Bronchial Diseases; Neoplasms; Respiratory Tract Diseases; Neoplasms, Glandular and Epithelial; Bronchial Neoplasms; Gemcitabine; Cisplatin; Carboplatin; Pembrolizumab; Pemetrexed; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents