soxataltinib (SY-5007) / Shouyao Holdings - LARVOL DELTA

Clinical efficacy and tolerability of the selective RET inhibitor soxataltinib (SY-5007) in advanced RET fusion–positive non–small cell lung cancer (NSCLC): Primary findings from a confirmatory phase III trial. (ASCO 2026) - P3 | "The primary analysis of this Phase III trial confirmed Soxataltinib as a highly effective and well-tolerated therapeutic agent for patients with RET fusion–positive NSCLC in the first-line setting. This observed high response rates and durable disease control benefit underscored its potential as a best-in-class RET inhibitor. The adverse event profile was predictable and manageable, supporting its feasibility for long-term administration."

Clinical • Metastases • P3 data • Cardiovascular • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Targeted Therapies in the Management of Advanced Medullary Thyroid Cancer. (PubMed, Oncologist) - "Targeted therapies have reshaped the management of advanced MTC, with selective RET inhibitors offering improved efficacy and tolerability. Continued research is essential to overcome resistance, expand therapeutic options, and improve patient outcomes."

IO biomarker • Journal • Neuroendocrine Tumor • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

Phase III Study of SY-5007, a RET Inhibitor, in Patients With Locally Advanced or Metastatic RET Fusion-positive NSCLC (clinicaltrials.gov) - P3 | N=120 | Active, not recruiting | Sponsor: Shouyao Holdings (Beijing) Co. LTD | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

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

Efficacy and safety of SY-5007, a highly selective RET inhibitor in RET fusion-positive NSCLC patients: Primary analysis from phase II study (ESMO 2025) - P1/2 | "A phase III study in untreated RET fusion-positive NSCLC is ongoing. Conclusions Treatment with SY-5007 demonstrated encouraging efficacy and durability, with mainly low-grade toxic effects in patients with RET fusion–positive NSCLC who were previously untreated or treated with systemic therapy for advanced disease."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

Overcoming resistance in RET-altered cancers through rational inhibitor design and combination therapies. (PubMed, Bioorg Chem) - "Traditional multi-kinase inhibitors (MKIs, such as cabozantinib and vandetanib) exhibit significant side effects due to non-selective inhibition of targets like VEGFR, and also suffer from resistance associated with RET mutations (e.g., V804L/M, G810C/S/R), both of which limit their clinical application...To overcome drug resistance, the design strategies of novel inhibitors focus on multi-target inhibition (such as PLM-101 targeting RET/YES1/FLT3, TPX-0046 targeting RET/SRC), structural optimization (such as helical ring derivatives enhancing binding stability), and natural compound screening (such as ZINC series molecules)...For instance, selpercatinib combined with crizotinib can inhibit MET amplification-driven resistance, while arsenic trioxide combined with pralsetinib restores sensitivity by inhibiting the HH-Gli pathway. Current clinical trials show that novel RET inhibitors such as SY-5007 have a significant objective response rate in advanced RET..."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGFR • FLT3 • MET • RET • STAT1

First-in-human, phase 1 dose-escalation and dose-expansion study of a RET inhibitor SY-5007 in patients with advanced RET-altered solid tumors. (PubMed, Signal Transduct Target Ther) - P1/2 | "In conclusion, SY-5007 was well-tolerated and showed promising efficacy in patients with RET-altered solid tumors. Serial ctDNA monitoring may unveil treatment response and potential resistance mechanisms (NCT05278364)."

Journal • Metastases • P1 data • Cardiovascular • Dyslipidemia • Endocrine Cancer • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Hypertension • Hypertriglyceridemia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma

Efficacy and safety of SY-5007, a highly potent and selective RET inhibitor, in Chinese patients with advanced RET-fusion positive non-small cell lung cancer (NSCLC): Results from a multicenter, single-arm, phase II study. (ASCO 2024) - P1/2 | "SY-5007 demonstrated promising efficacy and safety for advanced NSCLC with positive RET."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

A Study to Evaluate the Mass Balance of [14C] SY-5007 in Healthy Adult Male Subjects in China (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Shouyao Holdings (Beijing) Co. LTD

New P1 trial

A Study to Evaluate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of SY-5007 in Healthy Subjects (clinicaltrials.gov) - P1 | N=28 | Not yet recruiting | Sponsor: Shouyao Holdings (Beijing) Co. LTD

New P1 trial

A Study to Evaluate the Food Effects on Pharmacokinetics of SY-5007 Tablets in Healthy Subjects (clinicaltrials.gov) - P1 | N=28 | Not yet recruiting | Sponsor: Shouyao Holdings (Beijing) Co. LTD

New P1 trial

Phase III Study of SY-5007, a RET Inhibitor, in Patients With Locally Advanced or Metastatic RET Fusion-positive NSCLC (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Shouyao Holdings (Beijing) Co. LTD

Metastases • New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • RET

A first-in-human phase I, dose-escalation and dose-expansion study of SY-5007, a highly potent and selective RET inhibitor, in Chinese patients with advanced RET positive solid tumors. (ASCO 2023) - P1/2 | "Recently, selective RET TKIs, selpercatinib and pralsetinib, were approved for RET positive solid tumors by FDA. SY-5007 was well tolerated in patients. Preliminary antitumor activity was also observed in patients with advanced RET-fusion positive NSCLS and RET mutant MTC. The pivotal Phase II clinical study of SY-5007 in NSCLC patients is ongoing."

Clinical • Metastases • P1 data • Cardiovascular • Endocrine Cancer • Hypertension • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma • RET

Phase I/II Study of SY-5007, a RET Inhibitor, in Patients With RET-altered Advanced Solid Tumor (clinicaltrials.gov) - P1/2 | N=184 | Recruiting | Sponsor: Shouyao Holdings (Beijing) Co. LTD | Trial primary completion date: Mar 2023 ➔ Jan 2025

Metastases • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • PD-L1 • RET

Phase I/II Study of SY-5007, a RET Inhibitor, in Patients With RET-altered Advanced Solid Tumor. (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Shouyao Holdings (Beijing) Co. LTD | Phase classification: P1 ➔ P1/2 | N=80 ➔ 200 | Trial completion date: Jun 2023 ➔ Feb 2025

Enrollment change • Metastases • Phase classification • Trial completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • PD-L1 • RET

Shouyao Holdings (688197.SH): Selective RET Inhibitor SY-5007 Launches Pivotal Clinical Trial [Google translation] (Zhitong Finance) - "Zhitong Finance APP News, Shouyao Holdings...issued an announcement. Recently, the company received a communication application from the Center for Drug Evaluation (CDE) of the State Drug Administration regarding its selective RET inhibitor SY-5007. Qualification feedback, based on the safety and effectiveness data of SY-5007 at the current phase I, CDE agrees that SY-5007 will use phase II single-arm clinical trials in the future to apply for conditional approval for marketing. Accordingly, the company will quickly initiate a pivotal phase II clinical trial of SY-5007 for patients with RET-positive non-small cell lung cancer (NSCLC) after standard treatment."

New trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology

A Phase I Study to Evaluate the Safety, Pharmacokinetics and Efficacy of SY-5007 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Shouyao Holdings (Beijing) Co. LTD | Trial primary completion date: Mar 2022 ➔ Mar 2023

Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

A Phase I Study to Evaluate the Safety, Pharmacokinetics and Efficacy of SY-5007 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Shouyao Holdings (Beijing) Co. LTD

New P1 trial • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET