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

Efficacy and safety of pralsetinib in RET fusion-positive solid tumors: Data from the TAPISTRY trial. (ASCO-GI 2026) - P2 | "Funded by Hoffmann-La Roche, Rigel Pharmaceuticals, Inc. Clinical Trial Registration Number: NCT04589845 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Gastrointestinal Cancer • Oncology • 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

Launch Price Dynamics of Targeted Therapies in NSCLC: Dissecting the Cost and Value Across Biomarker Segments (ISPOR-EU 2025) - "The variation was evident even within mutation types highlighting potential discrepancies in value (e.g., ROS1: $7,760 [taletrectinib] to $9,693 [repotrectinib] to $13,019 [entrectinib]; RET: $11,393 [selpercatinib] to $15,859[pralsetinib]). Despite relatively consistent monthly costs, cost per mPFS month varies significantly within mutation groups. First-line therapies demonstrate superior value, supporting early biomarker testing. Emerging targeted therapies show potential for further improving value propositions through enhanced clinical outcomes."

Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • KRAS • ROS1

Identification of a Novel RET::FOXJ3 Fusion in Lung Adenocarcinoma Associated with Lack of Response to Pralsetinib. (PubMed, Cancer Lett) - "This case expands the current understanding of RET fusion partners and raises important questions regarding the functional and therapeutic implications of non-canonical fusions. It underscores the necessity of corroborating DNA-level findings with RNA and/or protein expression data and highlights the limitations of existing RET-targeted therapies for atypical RET fusions that may lack an intact kinase domain."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Palliative care • Solid Tumor • RET

GAVRETO net product sales were $11.1 million, growth of 56% compared to $7.1 million in the same period of 2024 (Rigel Press Release) - "For the third quarter ended September 30, 2025, total revenues were $69.5 million, consisting of $64.1 million in net product sales and $5.4 million in contract revenues from collaborations."

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

Design and Synthesis of 2-Aminopyrazolpyrimidopyridone Derivatives as RETV 804M and RETG 810C Kinase Inhibitors. (PubMed, Chem Biol Drug Des) - "The clinical therapeutic benefits of the second-generation RET inhibitor pralsetinib are greatly compromised by acquired resistance mediated by solvent-front mutations (e.g., RETG810R/S/C)...However, the relatively poor pharmacokinetic properties of these compounds will limit their further development. Therefore, compound 7qe might be a promising lead compound for the development of novel RETV804M and RETG810C inhibitors overcoming the clinical acquired resistance."

Journal • Oncology • CCDC6 • RET

FUNCTIONAL PRECISION MEDICINE REVEALS DRUG VULNERABILITIES IN PEDIATRIC SARCOMA (SIOP 2025) - "All tested RMS cell lines, including PAX3::FOXO1 fusion-positive RH30, were sensitive to PLK1 inhibitor volasertib (sDSSf ≥10). Filanesib, a mitotic inhibitor under clinical investigation, showed broad activity in RMS cell lines...Here, the primary tumor PDCs were responsive to carboplatin, decitabine, selumetinib, and RET inhibitor pralsetinib, while metastatic PDCs showed sensitivity to selumetinib, bortezomib, and vinorelbine. Conclusions As a conclusion, this study demonstrates that DSRT of patient-derived sarcoma cells, supported by well-defined control models, enables the identification of actionable drug sensitivities. Integrating FPM with next-generation sequencing may enhance personalized treatment strategies in pediatric sarcoma."

Clinical • Tumor mutational burden • Pediatrics • Rhabdomyosarcoma • Sarcoma • Solid Tumor • FOXO1 • PAX3 • PAX7 • TMB

NAUTIKA1: A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=99 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Mar 2029 ➔ May 2030 | Trial primary completion date: Dec 2025 ➔ Nov 2026

Biomarker • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • KRAS • NTRK1 • NTRK2 • NTRK3 • PD-L1 • RET • ROS1

Real-world evidence of resistance mechanisms, subsequent genome-guided treatments and late presenting adverse events in patients with RET-altered tumours on selective RET inhibitors (ESMO 2025) - "Results 53 pts (48 selpercatinib, 1 BOS172738, 1 selpercatinib & pralsetinib, 3 BOS172738 & pralsetinib) started RET TKI in Mar 2018 - Sep 2023 were included: 47 NSCLC (98% fusion; 2% exon 11 intron), 6 thyroid cancer (50% M918T, 33% fusion, 17% G634R/G533C). Optimal strategy for LPAE will be discussed. Legal entity responsible for the study The authors."

Adverse events • Clinical • HEOR • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • MET • NTRK

Real-world FAERS safety analysis of Pralsetinib. (PubMed, Sci Rep) - "New and unexpected signals of AEs with pralsetinib were also identified. For pralsetinib to be used as effectively as possible, prospective trials are required, and the drug's long-term safety should be regularly checked."

Journal • Real-world evidence • Cardiovascular • CNS Disorders • Cognitive Disorders • Developmental Disorders • Lung Cancer • Myocardial Infarction • Non Small Cell Lung Cancer • Oncology • Otorhinolaryngology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

NEXT-GENERATION SEQUENCING IN IDH-WILDTYPE GLIOBLASTOMA: A PATHWAY TO PRECISION THERAPEUTICS (EANO 2025) - "Two patients had PIK3CA mutation (targeted therapy Alpesilib), one patient has RET mutation (targeted therapy Selpercatinib & Pralsetinib), one patient had GOPC-ROS1 fusion (targeted therapy Crizotinib, Entrectinib & Repoctrectinib), one patient had PTPRZ1-MET fusion (targeted therapy Capmatinib & Tepotinib) and one patient had FGFR3-TACC3 fusion (targeted therapy Erdafitinib, Anlotinib, etc). However ongoing research is going on to overcome BBB like using nanocarriers, combination with immunotherapy or chemotherapy, etc. Although we have limitation of cases, 50% of our cases have shown mutation or fusion, against which targeted therapy is available. This holds future promise for targeted therapy for IDH-wild type glioblastoma."

Biomarker • IO biomarker • Next-generation sequencing • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • FGFR3 • PIK3CA • PTPRZ1 • RET • ROS1 • TACC3

Corneal edema and epithelial defect during pralsetinib treatment. (PubMed, J Oncol Pharm Pract) - "2 weeks later, the corneal findings improved and visual acuity increased. The patient was much better 1 months later.DiscussionThis case report describes corneal edema with epithelial defect as a rare side effect of pralsetinib and highlights the importance of collaboration between oncologists and ophthalmologists."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ophthalmology • Solid Tumor • RET

YAP-Driven Modulation of HER3-Mediated Adaptive Resistance to RET Inhibitors in RET-Altered Cancer (IASLC-WCLC 2025) - "Methods : Four RET-aberrant cancer cell lines were tested for sensitivity to selpercatinib and pralsetinib...In vivo, co-administration of selpercatinib and afatinib significantly suppressed tumor growth compared to selpercatinib alone...This novel therapeutic strategy has the potential to advance personalized medicine by refining patient selection and optimizing treatment regimens, ultimately leading to improved clinical outcomes for patients with RET-aberrant cancers. Further studies are warranted to validate these findings and explore the clinical applicability of YAP and HER3 inhibition in combination with RET-TKIs."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • ERBB3 • FGFR1 • MET • RET

Mechanisms of Resistance to Tyrosine Kinase Inhibitors in Lung Cancer Cells Harbouring RET Fusions (IASLC-WCLC 2025) - "In recent years, two selective RET tyrosine kinase inhibitors (TKIs) have been approved by the Food and Drug Administration (FDA), selpercatinib and pralsetinib. In addition, the activation of AKT and the clonal expansion of a new gene fusion suggest the existence of multiple simultaneous resistance mechanisms to RET-TKIs. Altogether, these observations can help us to better understand the resistance processes in order to design future strategies for the treatment of these patients"

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCDC6 • KIF5B • KRAS • NRAS • RET

Retrospective Multicenter Study Within the German Network Genomic Medicine Lung Cancer on RET Fusions as Resistance in EGFR-Mutant Lung Cancer (IASLC-WCLC 2025) - "For three patients, a combination of RET (Pralsetinib) and EGFR-TKIs (Osimertinib) was chosen, yielding a PFS of 3.9 months, 6.0 months (ongoing) and 10.5 months (ongoing)...However, following treatment with Osimertinib and Selpercatinib, neither alteration was detectable...Early detection via individualized EGFR and RET-specific cDNA-assay may enhance therapeutic decision-making. While combinatorial EGFR- and RET-TKI therapy holds promise, further research is essential to refine treatment strategies and evaluate long-term efficacy."

Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCDC6 • EGFR • KIF5B • NCOA4 • RET

RET Inhibitor Pralsetinib Suppresses TMZ-resistant Glioma Growth via Regulating of Spermine Production (Front Immunol) - "Further investigation revealed that pralsetinib, a selective RET inhibitor, exhibited significant antitumor activity against TMZ-resistant glioma cells both in vitro and in vivo. Mechanistically, pralsetinib inhibited the spermine-induced activation of the PI3K/AKT pathway and downregulated SMS expression, leading to reduced spermine production."

Preclinical • Glioma

Pralsetinib (Phase 1/2 ARROW Trial) Compared With Best Available Therapy (External Control) in Pretreated RET Fusion+ NSCLC (IASLC-WCLC 2025) - P1/2 | "Most frequently received BAT were tyrosine kinase inhibitors (66.7%; 29.6% investigational agents, 25.9% cabozantinib, 7.4% vandetanib, 3.7% alectinib) and chemotherapy (25.9%)...Conclusions : This RW, multi-center study found that 2L+ treatment with pralsetinib in advanced RET fusion-positive NSCLC was associated with higher ORR and significantly improved OS and PFS compared to BAT, even after adjusting for population differences. Limitations of RW data include missing data and potential unmeasured confounding, which this study aimed to mitigate through rigorous analytical methods."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • RET

Efficacy and Safety of Pralsetinib in Patients With Advanced Ret Fusion-Positive NSCLC: Phase 1/2 ARROW Study Final Data (IASLC-WCLC 2025) - P1/2 | "No new safety signals were identified with this update. Conclusions : 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."

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

A Retrospective and Prospective Real-world Study of Molecular Typing in the Treatment of Advanced Thyroid Cancer (clinicaltrials.gov) - P4 | N=800 | Recruiting | Sponsor: Fudan University | N=200 ➔ 800 | Trial completion date: Apr 2027 ➔ Dec 2028 | Trial primary completion date: Apr 2026 ➔ Dec 2026

Enrollment change • Real-world evidence • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma