SY-5007 / Shouyao Holdings - LARVOL DELTA

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