KEY TAKEAWAYS
- AcceleRET Lung is a Phase 3 trial evaluated the efficacy and safety of pralsetinib versus SOC for first-line treatment of advanced/metastatic RET fusion–positive NSCLC.
- Patients will be randomized 1:1 to 400 mg once daily of pralsetinib or SOC and stratified by the intended use of pembrolizumab, brain metastasis history, and Eastern Cooperative Oncology Group Performance Status.
- The trial’s primary endpoint was PFS.
- Secondary endpoints included ORR, OS, DOR, disease control rate, clinical benefit rate, time to intracranial progression, intracranial ORR, safety/tolerability, and quality of life evaluations.
- Recruitment has begun with sites (active or planned) in North America, Central America, Europe, and Asia.
This first-line treatment of advanced/metastatic RET fusion-positive NSCLC is being evaluated in this worldwide, open-label, randomized, phase 3 research AcceleRET Lung (NCT04222972) study. An estimated 1-2% of all non-small cell lung cancer cases are caused by fusions in the RET gene (NSCLC). Based on the phase 1/2 ARROW study results, the FDA and EMA have approved pralsetinib for treating patients with metastatic RET fusion-positive NSCLC (NCT03037385). Patients who started pralsetinib at 400 mg QD after platinum-based chemotherapy in the ARROW study (data cutoff: November 6, 2020) had an ORR of 62%, as determined by a central review of the data. The overall response rate was 79% in the untreated population. Most treatment-related side effects were mild to moderate across the 400 mg QD (n=471) safety population.
Around 226 individuals diagnosed with metastatic RETfusion-positive non-small cell lung cancer (NSCLC) will be randomly assigned in a 1:1 ratio to either receive oral pralsetinib at a dosage of 400 mg once daily or standard of care treatment. For patients with non-squamous histology, the standard of care treatment will consist of platinum/pemetrexed ± pembrolizumab, followed by maintenance pemetrexed ± pembrolizumab at the discretion of the investigator. For patients with squamous histology, the standard of care treatment will consist of platinum/gemcitabine or platinum plus pembrolizumab plus paclitaxel/nab-paclitaxel, followed by maintenance pembrolizumab. Stratification criteria include Pembrolizumab intent, brain metastasis history, and Eastern Cooperative Oncology Group performance status. Patients must have had no prior systemic treatment for advanced/metastatic NSCLC, had a tumor assessed as RET fusion-positive either locally or centrally, had no other actionable oncogenic drivers, and had not received a selective RET inhibitor before the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Individuals with brain metastases were allowed, provided they were asymptomatic and taking a steady dose of corticosteroids. Patients assigned to SOC can switch to pralsetinib treatment if and when their condition worsens. Progression-free survival is the key measure of efficacy (blinded independent central review; RECIST v1.1). The overall response rate (ORR), overall survival (OS), duration of response (Duration), disease control rate (DCR), clinical benefit rate (CBR), time to intracranial progression (Time), intracranial ORR (Oral Response Rate), safety/tolerability, and quality of life assessments are secondary endpoints. Exploratory endpoints included the identification of possible biomarkers of antineoplastic action and resistance. North America, Central America, Europe, and Asia are open (or soon-to-be) recruitment hotspots.
Source: https://meetings.asco.org/abstracts-presentations/213249
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04222972
J Clin Oncol 40, 2022 (suppl 16; abstr TPS9159)
