AcceleRET Lung: A phase 3 study of first-line pralsetinib in patients with RET fusion–positive advanced/metastatic NSCLC.

Abstract

TPS9159 Background: RET gene fusions have been identified as oncogenic drivers in multiple tumor types, including 1–2% of non-small cell lung cancer (NSCLC). Pralsetinib is a potent, selective RET inhibitor, approved in the US and EU for the treatment of metastatic RET fusion–positive NSCLC based on the phase 1/2 ARROW study (NCT03037385). In the ARROW study (data cutoff: Nov 6, 2020), patients who initiated 400 mg once daily (QD) of pralsetinib after platinum-based chemotherapy achieved an overall response rate (ORR) of 62%, per independent central review. In the treatment-naïve group, the ORR was 79%. Most treatment-related adverse events were grade 1–2 across the entire safety population treated at 400 mg QD (n=471). AcceleRET Lung, an international, open-label, randomized, phase 3 study (NCT04222972), will evaluate the efficacy and safety of pralsetinib versus standard of care (SOC) for first-line treatment of advanced/metastatic RET fusion–positive NSCLC. Abstracts for this study were previously submitted to the European Lung Cancer Congress 2020, the American Society of Clinical Oncology 2020 annual meeting, and 2020 World Conference on Lung Cancer. Methods: Approximately 226 patients with metastatic RET fusion–positive NSCLC will be randomized 1:1 to oral pralsetinib (400 mg QD) or SOC (non-squamous histology: platinum/pemetrexed ± pembrolizumab followed by maintenance pemetrexed ± pembrolizumab [at investigator’s discretion]; squamous histology: platinum/gemcitabine or platinum + pembrolizumab + paclitaxel/nab-paclitaxel followed by maintenance pembrolizumab). Stratification factors include intended use of pembrolizumab, history of brain metastases, and Eastern Cooperative Oncology Group Performance Status. Key eligibility criteria include no prior systemic treatment for advanced/metastatic NSCLC; RET fusion–positive tumor by local or central assessment; no additional actionable oncogenic drivers; no prior selective RET inhibitor; measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients with central nervous system metastases were permitted if asymptomatic and on a stable dose of corticosteroids. Cross-over to receive pralsetinib upon disease progression will be permitted for patients randomized to SOC. The primary endpoint is progression-free survival (blinded independent central review; RECIST v1.1). Secondary endpoints include ORR, overall survival, duration of response, disease control rate, clinical benefit rate, time to intracranial progression, intracranial ORR, safety/tolerability and quality of life evaluations. Identification of potential biomarkers of antineoplastic activity and resistance was an exploratory endpoint. Recruitment has begun with sites (active or planned) in North America, Central America, Europe and Asia. Clinical trial information: NCT04222972.

Pralsetinib (Gavreto)

“…Patients will be enrolled in approximately 97 sites in across the Americas (including Canada), Asia, Europe, and Oceania. [32][33][34] • Aged 18 years and older • Pathologically confirmed, definitively diagnosed, locally advanced (not able to be treated with surgery or radiotherapy) or metastatic NSCLC that has not been treated with systemic anticancer therapy for metastatic disease RET gene fusion in tumour and/or blood from laboratory…”

“…AcceleRET-Lung, 32 Besse et al� (2021), 33 The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date� For clinical studies with more than a primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures� b The date on which the last participant in a clinical study was examined or received an intervention or treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit)� Source: AcceleRET-Lung, 32 Besse et al� (2021), 33 and Popat et al� (2022)� 34 This study is currently recruiting participants, with a planned enrolment of approximately 226 patients. The estimated primary completion date (on which the last participant in a clinical study will be examined or receive an intervention to collect final data for the primary outcome measure) and study completion date (on which the last participant in a clinical study will be examined or receive an intervention or treatment to collect final data for the primary outcome measures, secondary outcome measures, and AEs) are September 30, 2023, and December 31, 2024, respectively.…”

“…For nonsquamous histology, the treatment regimen will be carboplatin or cisplatin plus pemetrexed (with vitamin supplementation) with or without pembrolizumab followed by optional pemetrexed (with vitamin supplementation) maintenance with or without pembrolizumab; for squamous histology, the treatment regimen will be either carboplatin or cisplatin plus gemcitabine, or carboplatin with paclitaxel plus nab-paclitaxel and pembrolizumab followed by maintenance pembrolizumab. [32][33][34] Stratification factors include intended use of pembrolizumab, history of brain metastases, and ECOG PS. Key eligibility criteria include no prior systemic treatment for advanced and/ or metastatic NSCLC; RET fusion-positive tumour by local or central assessment; no additional actionable oncogenic drivers; no prior selective RET inhibitor; and measurable disease as defined by RECIST 1.1.…”

“…Crossing over to receive pralsetinib upon disease progression will be permitted for patients randomized to the SOC arm. [32][33][34] The primary end point is PFS (defined by RECIST 1.1) assessed by a BICR, whereas the secondary end points include ORR, OS, DOR, disease control rate, clinical benefit rate, time to intracranial progression, intracranial ORR, safety and tolerability, and quality of life evaluations. Identification of potential biomarkers of antineoplastic activity and resistance is an exploratory end point.…”

“…Identification of potential biomarkers of antineoplastic activity and resistance is an exploratory end point. [32][33][34]…”