Gavreto (pralsetinib) / CStone Pharma, Allist, Rigel Pharmaceuticals, Sanofi - LARVOL DELTA

Safety evaluation of selective RET inhibitors in patients with lung cancer: a real-world pharmacovigilance study. (PubMed, Tumori) - "This study provides critical insights into the established and potential adverse events associated with selpercatinib and pralsetinib. The findings offer valuable evidence to guide the clinical use of RET inhibitors."

Adverse events • Journal • Real-world evidence • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROR1

Efficacy and safety of pralsetinib in patients with advanced RET-fusion-positive NSCLC: Final data from the phase 1/2 ARROW study. (ASCO 2025) - P1/2 | "Pralsetinib produced clinically meaningful and durable responses in patients with RET-fusion-positive NSCLC (regardless of prior therapies) with a manageable safety profile, confirming with this longer follow up previously published results. aPer FDA censoring rule."

Clinical • Metastases • P1/2 data • Anemia • Hypertension • Infectious Disease • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • RET

Efficacy and safety of pralsetinib in multiple endocrine neoplasia type 2-associated pheochromocytoma: a case report. (PubMed, Ther Adv Endocrinol Metab) - "Over 16 months of pralsetinib therapy, we found that the patient achieved sustained therapeutic benefits, specifically characterized by symptomatic relief, significant reduction in hormone levels, and shrinkage of the left adrenal masses. These findings indicate that pralsetinib is effective and safe for treating pheochromocytomas associated with RET missense mutation, but further clinical practices are warranted to confirm its efficacy and safety profile."

Journal • Oncology • Solid Tumor • RET

A Prospective, Single-Arm Clinical Study to Evaluate the Efficacy and Safety of Pralsetinib in Conversion Surgery for Locally Advanced RET Fusion-Positive NSCLC (ChiCTR) - P=N/A | N=15 | Not yet recruiting | Sponsor: West China Hospital of Sichuan Universit; West China Hospital of Sichuan Universit

New trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Addressing challenges with real-world synthetic control arms to demonstrate the comparative effectiveness of Pralsetinib in non-small cell lung cancer. (PubMed, Nat Commun) - P1/2 | "Using the example of pralsetinib from a RET fusion-positive aNSCLC single-arm trial (NCT03037385), we demonstrate a relative survival benefit when compared to pembrolizumab monotherapy and pembrolizumab with chemotherapy RWD cohorts. Overall, the study provides evidence in favour of pralsetinib as a first-line treatment for RET fusion-positive aNSCLC. The quantification of potential bias performed in this study can be used as a template for future studies of this nature."

HEOR • Journal • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Efficacy and safety of pralsetinib in RET fusion-positive solid tumors: Final data from the ARROW trial. (ASCO 2025) - P1/2 | "In the phase 2 portion of this trial, responses were observed in many tumor types (Table). Pralsetinib demonstrated robust and durable anti-tumor activity with an ORR of 46.4%. These data validate RET fusions as a tissue-agnostic target with sensitivity to RET inhibition and activity beyond NSCLC and thyroid cancer, further supporting the promising potential of pralsetinib to address the unmet medical need in these patients."

Clinical • Anemia • Endocrine Cancer • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thyroid Gland Carcinoma • RET

Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. (PubMed, Nat Med) - P1/2 | "The most common grade ≥3 treatment-related adverse events were neutropenia (31%) and anemia (14%). These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition, indicating pralsetinib's potential as a well-tolerated treatment option with rapid, robust and durable anti-tumor activity in patients with diverse RET fusion-positive solid tumors."

Journal • P1/2 data • Pan tumor • Endocrine Cancer • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • CCDC6 • KIF5B • NCOA4 • RET

Safety and efficacy of pralsetinib in RET fusion-positive non-small cell lung cancer including as first-line therapy: update from the ARROW trial. (PubMed, Ann Oncol) - P3 | "Pralsetinib treatment produced robust efficacy and was generally well tolerated in treatment-naïve patients with advanced RET fusion-positive NSCLC. Results from the confirmatory phase III AcceleRET Lung study (NCT04222972) of pralsetinib versus standard of care in the first-line setting are pending."

Journal • Cardiovascular • Hematological Disorders • Hypertension • Immunology • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Landscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium. (PubMed, Clin Cancer Res) - "Prevalence of secondary RET mutations after SRIs was low, underscoring greater role for off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream regulators of MAPK and PI3K pathways were identified, most commonly MET amplification. Continued efforts to characterize SRI resistance biology are critical to guide development of novel therapeutic strategies."

Journal • Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • CDKN2A • CDKN2B • KEAP1 • KRAS • MET • RET • TP53

Real-World Outcomes of RET Inhibitor Switching in RET Fusion–Positive NSCLC Patients (IASLC-TTLC 2026) - "BACKGROUND The receptor tyrosine kinase RET (REarranged during Transfection) inhibitors (RETi) pralsetinib and selpercatinib are approved for metastatic RET fusion positive NSCLC. CONCLUSION Among patients who switched RETi's due to an AE, response rates exceeded 60%, aligning with the 50% response rate observed in the RET MAP registry. Collectively, these results underscore that switching from one RET inhibitor to another can be efficacious, particularly for patients who must discontinue initial therapy because of adverse events."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • RET

Landscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium (IASLC-TTLC 2026) - "Selective RET inhibitors (SRIs) selpercatinib and pralsetinib have transformed outcomes for patients with RET-altered malignancies. In RETgistry, secondary RET mutations after SRIs were uncommon, underscoring predominance of off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream MAPK and PI3K regulators were identified, with MET amplification being the most common. Continued efforts to characterize SRI resistance biology are critical to guide development of novel therapeutic strategies."

Clinical • Lung Cancer • Oncology • Solid Tumor • KEAP1 • KRAS • MET • PI3K • RET • TP53

Intestinal Lymphangiectasia with RET Tyrosine Kinase Inhibitor Therapy (IASLC-TTLC 2026) - "– As selpercatinib and pralsetinib use has gradually increased as first-line therapy for RET-altered non–small cell lung cancer (NSCLC), a growing number of adverse effects are being observed. Conclusion. - IL is a relatively frequent complication of RET TKI therapy, commonly associated with gastrointestinal symptoms and protein loss, highlighting the importance of early detection and individualized management."

Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor

Intracranial Efficacy of Pralsetinib in Patients With RET Fusion-Positive NSCLC: ARROW Study Subanalysis (IASLC-TTLC 2026) - P1/2 | "Pralsetinib demonstrated a CNS ORR of 55%, including 5 CRs, and a median response duration of 14.8 months, supporting its clinical utility in the treatment of RET fusion-positive NSCLC with CNS involvement."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • RET

Patterns of Tyrosine Kinase Inhibitor–Associated Pneumonitis in EGFR-Mutated and Other Driver-Positive NSCLC (IASLC-TTLC 2026) - "Pneumonitis was also diagnosed in patients with MET Exon 14 skipping mutation (capmatinib four patients of 40, 10%), RET (selpercatinib two patients and pralsetinib one patient of 12, 25%), and ROS1 (entrectinib one patient of 12, 8.3%). We reviewed electronic medical records of 476 patients with AGA metastatic NSCLC. Among them, 27 patients (5.67%) developed pneumonitis of varying grades (1-3). The majority of patients, 348, had EGFR mutations."

Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • MET • ROS1

Activity of Bevacizumab Combined With Chemotherapy in Advanced RET-Rearranged Non-Small Cell Lung Cancer (IASLC-TTLC 2026) - "Functional studies used selpercatinib- and pralsetinib-resistant Lc2/AD-derived cell lines (BluR, LoxoR) exposed to bevacizumab ± platinum-based chemotherapy, assessing vasculogenic mimicry, 3D spheroid viability, apoptosis and migration...SRI-resistant cells exhibited VEGF-axis hyperactivation (↑VEGFA/VEGFC; ↑p-VEGFR1/2) and intrinsic vasculogenic mimicry; bevacizumab impaired mimicry dose-dependently and, combined with carboplatin/pemetrexed or carboplatin/paclitaxel, reduced viability, increased apoptosis, limited migration, and shrank viable spheroid cores (Figure C)... These findings reveal angiogenesis as a therapeutic vulnerability in RET-rearranged NSCLC and support bevacizumab plus chemotherapy as a clinically meaningful strategy where selective RET inhibitors are unavailable or after resistance, providing a compelling rationale for clinical trials testing angiogenesis inhibition in this underserved population."

IO biomarker • Metastases • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FLT1 • KDR • VEGFC

Rigel expects to report fourth quarter of 2025 gross product sales of $84.5 million. Net product sales are expected to be $65.4 million, compared to $46.5 million for the same period of 2024, including (Rigel Press Release) - "TAVALISSE (fostamatinib disodium hexahydrate) net product sales of $45.6 million...GAVRETO (pralsetinib) net product sales of $10.2 million....REZLIDHIA (olutasidenib) net product sales of $9.6 million compared to $7.4 million for the same period of 2024."

Sales projection • Acute Myelogenous Leukemia • Immune Thrombocytopenic Purpura • Non Small Cell Lung Cancer

Pralsetinib-Induced Lymphocytic Colitis. (PubMed, ACG Case Rep J) - "We report a case of pralsetinib-induced LC in a patient with stage 3c nonsmall cell lung cancer. This case highlights pralsetinib-induced LC as a cause of persistent diarrhea that is refractory to standard antidiarrheal treatments and prompts gastrointestinal evaluation and histopathological examination to facilitate early diagnosis and management."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Onco360, the nation’s leading independent specialty pharmacy, has been chosen by Rigel Pharmaceuticals as limited distribution specialty pharmacy partner for TAVALISSE (fostamatinib disodium hexahydrate), GAVRETO (pralsetinib), and REZLIDHIA (olutasidenib) (GlobeNewswire)

Licensing / partnership • Acute Myelogenous Leukemia • Immune Thrombocytopenic Purpura • Non Small Cell Lung Cancer • Thyroid Gland Medullary Carcinoma

Efficacy and safety of pralsetinib in RET fusion-positive solid tumors: Data from the TAPISTRY trial. (ASCO-GI 2026) - P2 | "Pralsetinib demonstrated robust and durable activity against RET fusion-positive solid tumors, including GI tumors, with an ORR of 67%. These data validate RET fusions as a tissue-agnostic target with sensitivity to RET inhibition, suggesting the potential therapeutic utility of pralsetinib in these patients. Efficacy summary."

Clinical • Biliary Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • RET

CStone today announced that GAVRETO (pralsetinib, 100 mg) has been included in the latest National Reimbursement Drug List (NRDL), released by China’s National Healthcare Security Administration (HKEXnews) - "The most recent NRDL will become effective on January 1, 2026."

Reimbursement • Non Small Cell Lung Cancer • Thyroid Gland Medullary Carcinoma

Review and analysis of clinical trials of selective RET inhibitors for the treatment of thyroid cancer. (PubMed, Front Oncol) - "Selpercatinib and pralsetinib are the most frequently studied RET inhibitors. Notably, research on next-generation RET inhibitors as monotherapy approaches (e.g., LOXO-260, enbezotinib, SY-5007 and TY-1091) is currently underway...While selective RET inhibitors have demonstrated therapeutic potential, concerns regarding drug resistance and toxicity persist. Therefore, future strategies should prioritize the development of next-generation inhibitors and the optimization of combination regimens to improve outcomes for RET-altered thyroid cancer patients."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • RET

RET Receptor Tyrosine Kinase Promotes Breast Cancer Metastasis to the Brain and RET Inhibitors Pralsetinib and Selpercatinib Suppress Breast Cancer Brain Metastases. (PubMed, bioRxiv) - "Using two mouse studies that model multi-organ metastases and breast tumor formation in the brain, we observed that RET inhibition significantly prevented the circulating tumor cells from forming brain metastases and suppressed the growth of intracranially implanted tumor cells, but did not significantly inhibit the progression of well-established brain metastases. Together, our findings demonstrated that RET is highly activated in BCBM and functioning as a novel mediator of BCBM, and that RET plays a new role as a viable therapeutic target for BCBM."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • CTCs • HER-2 • RET

Discovery of Piperazine-Amide Derivatives as Highly Potent and Selective RET Inhibitors. (PubMed, ACS Med Chem Lett) - "Herein, we report a series of compounds featuring a novel piperazine-amide scaffold, designed and synthesized from BLU-667 via sequential bioisosteric replacement, linkage truncation, and subsequent structure-activity relationship (SAR) optimization...Furthermore, it exhibited favorable oral pharmacokinetic properties in mice, demonstrating superior in vivo efficacy compared to the multikinase inhibitor cabozantinib. In conclusion, compound 13 is a promising preclinical candidate."

Journal • Oncology • KDR • RET

The RET inhibitor pralsetinib suppresses TMZ-resistant glioma growth by regulating spermine production. (PubMed, Front Pharmacol) - "Although temozolomide (TMZ)-based adjuvant treatment has improved overall patient survival, clinical outcomes remain unsatisfactory. Mechanistically, pralsetinib inhibited the spermine-induced activation of the PI3K/AKT pathway and downregulated SMS expression, leading to reduced spermine production. Our findings reveal the role of spermine in TMZ-resistant glioma and suggest a potential new pharmacological application for pralsetinib in the glioma treatment."

Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Pathological complete response in RET-positive non-small cell lung cancer: a case report of pralsetinib-based "sandwich" therapy. (PubMed, Transl Lung Cancer Res) - "Incorporating targeted therapy with surgery and tailored adjuvant treatment may lead to durable remission in selected patients with locally advanced disease. Prospective studies need to be conducted to further define the treatment sequencing and validate this multi-modal approach."

Journal • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • RET