Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced <i>RET</i> Fusion–Positive Non–Small Cell Lung Cancer

<i>RET</i> fusions appear in 1%-2% of non-small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic <i>RET</i>-altered NSCLC and <i>RET</i> fusion-positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in <i>RET</i> fusion-positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with <i>RET</i> fusion-positive NSCLCs, confirming previous findings with longer follow-up.

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Journal
Journal of Clinical Oncology
Published
2026-03-26
DOI
https://doi.org/10.1200/jco-25-01489
Primary Topic
Lung Cancer Treatments and Mutations
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article
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article

Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced RET Fusion–Positive Non–Small Cell Lung Cancer

Sophia Ying Wang, Anthonie J. van der Wekken, Mohit Narang, Amber Thomassen et al.
Journal of Clinical Oncology
Lung Cancer Treatments and Mutations
article

Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced RET Fusion–Positive Non–Small Cell Lung Cancer

Sophia Ying Wang, Anthonie J. van der Wekken, Mohit Narang, Amber Thomassen, Matthew H. Taylor, Robert C. Doebele, Jason M. Melear, Stephen V. Liu, G. Curigliano, Christina S. Baik, Gregory P. Kalemkerian, Gilberto Lopes, G. Alonso, Yanyan Lou, Makenzi Colleen Evangelist, Daniel W. Bowles, S.-H.I. Ou, Justin F. Gainor, Luis Paz-Ares, Shirish M. Gadgeel, Dong-Wan Kim, Ashish Saxena, Julien Mazières, Benjamin Besse, Michael Thomas, Carlos R. Becerra, Daniel S.W. Tan, Vivek Subbiah, Dae Ho Lee, Aaron S. Mansfield, Frank Griesinger
article en

Abstract

<i>RET</i> fusions appear in 1%-2% of non-small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic <i>RET</i>-altered NSCLC and <i>RET</i> fusion-positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in <i>RET</i> fusion-positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with <i>RET</i> fusion-positive NSCLCs, confirming previous findings with longer follow-up.

Journal of Clinical Oncology
Ulsan College (KR), Hebron University (PS), Hoag Memorial Hospital Presbyterian (US), University Medical Center Groningen (NL), The University of Texas MD Anderson Cancer Center (US), Université Toulouse III - Paul Sabatier (FR), University of Miami (US), Henry Ford Health System (US), University of Groningen (NL), Georgetown University (US), University of Milan (IT), University of California, Irvine (US), Cornell University (US), Heidelberg University (DE), Université Paris-Saclay (FR), University of Michigan (US), Providence Portland Medical Center (US), Asan Medical Center (KR), Institut Gustave Roussy (FR), University of Washington Medical Center (US), University Hospital Heidelberg (DE), Seoul National University Hospital (KR), Henry Ford Hospital (US), Centre Hospitalier Universitaire de Toulouse (FR), University of Ulsan (KR), Massachusetts General Hospital (US), Maryland Oncology Hematology (US), Sarah Cannon (US), Hospital Universitario 12 De Octubre (ES), National Center for Tumor Diseases (DE), Michigan Medicine (US), New York Oncology Hematology (US), Mayo Clinic in Arizona (US), Pius Hospital Oldenburg (DE), Vall d'Hebron Hospital Universitari (ES), German Center for Lung Research (DE), University of Colorado Cancer Center (US), National Cancer Centre Singapore (SG), Mayo Clinic in Florida (US), The US Oncology Network (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Sylvester Comprehensive Cancer Center (US), European Institute of Oncology (IT), Sunesis (United States) (US), University of Colorado Denver (US)
Good health and well-being
Openalex Percentile: Top 7%
Lung Cancer Treatments and Mutations
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