Pralsetinib induced robust and durable responses with a manageable safety profile, reinforcing the benefits of selective RET inhibitors in treating RET fusion-positive NSCLC
On March 31, 2026, Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial-stage biotechnology company focused on hematologic disorders and cancer, announced publication of the final data from the Phase 1/2 ARROW study evaluating pralsetinib for the treatment of metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) in the Journal of Clinical Oncology. The final data includes an additional 42 months of follow-up from previously published data. Pralsetinib is the only once daily, oral RET-inhibitor therapy that is designed to selectively target RET in metastatic NSCLC and advanced or metastatic thyroid carcinoma.
“The final data from the ARROW study shows robust and durable responses with a manageable safety profile in patients with RET fusion-positive NSCLC, emphasizing the importance of early biomarker testing and suggesting that pralsetinib may be a valuable tool in the treatment armamentarium,” said Justin F. Gainor, MD, Phase 1/2 trial investigator and Director of the Center for Thoracic Cancers at Mass General Brigham Cancer Institute. “In addition, the responses observed in the subset of patients with measurable CNS metastases at baseline further expand the potential clinical value of pralsetinib in everyday practice.”
“The results published in the Journal of Clinical Oncology demonstrate the positive impact pralsetinib can have for patients with RET fusion-positive NSCLC,” said Lisa Rojkjaer, MD, Rigel’s chief medical. “These longer-term data further support pralsetinib’s role as a first-line treatment option for RET fusion-positive NSCLC patients.”
Additional key points from the paper include:
- Consistent with previous reports from the ARROW study NSCLC cohort, pralsetinib was generally well tolerated with a manageable toxicity profile. Three treatment-related deaths occurred in treatment-naive patients in Asia (pneumonia, n=2; interstitial lung disease and rhabdomyolysis, n=1 each), no new safety signals were observed and no hypersensitivity reactions were reported in patients receiving prior immunotherapies.
- Among patients with measurable disease (n=259), the overall response rate (ORR) was 70%, including 7% complete responses and 63% partial responses.
- ORR was 78% among treatment-naïve patients and 63% among patients receiving prior platinum-based chemotherapy.
- At final data lock, median treatment duration was 15.0 months.
- Median overall survival (OS) was 44.3 months in the overall measurable disease patient population, 50.1 months in treatment-naïve patients, and 39.7 months in prior-platinum patients, with median follow-ups of 47.6, 43.7, and 49.7 months, respectively. Longer median OS in the overall measurable disease patient population was seen in patients treated in the United States (62.4 months) vs. Asia (44.5 months) or Europe (29.6 months).
- Median overall progression-free survival (PFS) was 13.1 months in the overall measurable disease patient population, but was longer in patients in the United States (25.9 months) vs. Asia (12.6 months) or Europe (12.8 months).
- ORR remained high in subgroups bearing the RET fusion partners KI5FB and CCDC6 among both treatment-naive and prior platinum-based chemotherapy patients. Among all patients, median duration of response (DOR) was longer in patients with CCDC6 (47.9 months) vs. KIF5B (13.1 months).
- Fifteen patients had measurable central nervous system (CNS) metastases at baseline. The intracranial response rate (CNS ORR) among these patients was 53%. In the 11 response-evaluable patients with CNS metastases, CNS ORR was 73%.
The open-access publication, titled “Final Efficacy and Safety Data from the Phase 1/2 ARROW Study of Pralsetinib in Patients with Advanced RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC),” was published March 26, 2026 online and can be found here.
About NSCLC
It is estimated that over 229,000 adults in the U.S. will be diagnosed with lung cancer in 2026. Lung cancer is the leading cause of cancer death in the U.S., with non-small cell lung cancer (NSCLC) being the most common type accounting for 77% of all lung cancer diagnoses.1 RET fusions are implicated in approximately 1-2% of patients with NSCLC.2
About GAVRETO® (pralsetinib)
INDICATIONS
GAVRETO (pralsetinib) is indicated for the treatment of:
- Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test
- Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)*
*This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
About Rigel
Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing, and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company’s marketed products and pipeline of potential products, visit www.rigel.com.
- The American Cancer Society. Key Statistics for Lung Cancer. Revised January 13, 2026. Accessed March 27, 2026: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
- Kato, S. et al. RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients. Clin Cancer Res. 2017;23(8):1988-1997 doi: 10.1158/1078-0432.CCR-16-1679