NCT07514065

TSL2109 Capsules in Advanced Solid Tumor Patients: Safety, Tolerability, PK and Preliminary Efficacy

Multicenter, Dose-Escalation & Dose-Expansion, Single-Arm, Open-Label Phase I Trial: Safety, Tolerability, PK and Preliminary Antitumor Efficacy of TSL2109 Capsules in Advanced Solid Tumor Patients

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 78 (estimated)
• Sponsor: Tasly Pharmaceutical Group Co., Ltd · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

TSL2109 is a novel CDK4/6-DYRK2 dual-target inhibitor developed by Jiangsu Tasly Diyee Pharmaceutical Co., Ltd. for solid tumor treatment. Preclinical studies confirm its selective targeting of CDK4/6 and DYRK2, a eukaryotic CMGC family kinase. In palbociclib-resistant cell lines, TSL2109 downregulates cell cycle-related proteins and DYRK2 pathway ribosomal synthesis regulators (RRS1, CDK2), and upregulates p53, thus exerting synergistic antitumor effects and overcoming resistance to enzalutamide and palbociclib. As a small-molecule inhibitor with novel targets, structure and mechanism, TSL2109 blocks tumor cell cycle progression independently of hormonal signaling. Preclinical studies show it overcomes AR inhibitor resistance, meeting unmet needs for prostate cancer patients progressing after AR inhibitor therapy. It also reduces CDK2 activity and blocks CDK4/6 compensatory mechanisms, reversing resistance to CDK4/6 inhibitors, providing a new option for HR+/HER2- advanced breast cancer patients. Participants Dose-Escalation Phase: Advanced solid tumor patients, prioritizing metastatic castration-resistant prostate cancer (mCRPC) and HR+/HER2- advanced breast cancer. Dose-Expansion Phase: Cohort A/C: mCRPC; Cohort B/D: HR+/HER2- advanced breast cancer. Treatment Regimens C0 Cycle (3 days): Single oral dose on Day 1 morning under fasting, followed by 72-hour observation. C1 Cycle (28 days): Daily fasting oral dosing (QD) for 3 weeks, then 1-week rest. Participants may continue treatment if no DLT and potential clinical benefit. Dose escalation to a pre-established tolerable level is allowed per investigator-sponsor agreement if well-tolerated and likely beneficial. Treatment continues until disease progression, intolerable toxicity or new antitumor therapy. The Dose-Expansion Phase uses the same regimen as C1. Missed Dose: Make-up within 8 hours; skip if delayed over 8 hours. Notes: Once MTD is determined, participants dosed above MTD will be adjusted to MTD. All doses are administered orally under fasting conditions.

Detailed description

TSL2109 is a novel dual-target inhibitor of Cyclin-Dependent Kinase 4/6-Dualspecificity tyrosine-(Y)-phosphorylation Regulated Kinase 2 (CDK4/6-DYRK2) developed by Jiangsu Tasly Diyee Pharmaceutical Co., Ltd., intended for the treatment of solid tumors. Preclinical studies have demonstrated that TSL2109 selectively targets CDK4/6 and DYRK2, where DYRK2 (Dual-specificity tyrosine-phosphorylation regulated kinase 2) belongs to the CMGC family of the eukaryotic kinome. In vitro treatment of palbociclib-resistant cell lines with TSL2109 induced downregulation of cell cycle-related proteins and downstream ribosomal synthesis regulatory proteins of the DYRK2 signaling pathway, including Regulator of Ribosome Synthesis 1 (RRS1) and Recombinant Cyclin-Dependent Kinase 2 (CDK2), while simultaneously upregulating Recombinant Tumor Protein P53 (p53), thereby exerting synergistic antitumor effects and overcoming resistance to enzalutamide and palbociclib.This product is a selective small-molecule inhibitor of DYRK2 and CDK4/6 based on novel anticancer targets, novel chemical structure, and novel mechanism of action. Selective inhibition of DYRK2 and CDK4/6 can block tumor cell cycle progression independent of hormonal signaling pathways. In vitro and in vivo animal experiments have demonstrated promising efficacy in overcoming resistance to androgen receptor (AR) inhibitors, addressing the unmet clinical need for prostate cancer patients who have progressed following AR inhibitor therapy. Secondly, selective inhibition of DYRK2 can reduce CDK2 activity and block CDK4/6 compensatory mechanisms, with in vitro and in vivo animal experiments showing efficacy in overcoming resistance to CDK4/6 inhibitors. This addresses the treatment challenge for patients with HR+/HER2- advanced breast cancer who have progressed following CDK4/6 inhibitor therapy, providing a novel therapeutic option for HR+/HER2- breast cancer patients. Participants: Dose-Escalation Phase: Patients with advanced solid tumors, with priority given to those with metastatic castration-resistant prostate cancer (mCRPC) and HR+/HER2- advanced breast cancer. Dose-Expansion Phase: Cohort A and/or Cohort C: Metastatic castration-resistant prostate cancer (mCRPC) Cohort B and/or Cohort D: HR+/HER2- advanced breast cancer C0 Treatment Cycle (3 days): Oral administration on the morning of Day 1 under fasting conditions, followed by 72-hour observation. C1 Treatment Cycle (28 days): Multiple doses administered under fasting conditions, with daily dosing (QD) for 3 weeks followed by a 1-week treatment-free interval. If no dose-limiting toxicity (DLT) occurs during the DLT observation period and the investigator determines that continued treatment may provide benefit, the participant may continue receiving study treatment. During subsequent treatment, if the investigator determines based on available safety and efficacy data that increasing the dose may enhance potential benefit for the participant, and the participant has demonstrated good tolerability, the dose level may be escalated to a previously established tolerable dose following discussion between the investigator and sponsor. Treatment may continue until disease progression, intolerable toxicity, or initiation of new antitumor therapy. Dose-Expansion Phase: The same dosing regimen as C1. Missed Dose: Make-up dosing is permitted within 8 hours; if more than 8 hours have elapsed, the missed dose should be skipped. Notes: Participants previously enrolled at dose levels above the maximum tolerated dose (MTD) will have their subsequent doses adjusted to the MTD dose level once the MTD is established. Administered orally under fasting conditions.

Conditions

• Metastatic Castration-Resistant Prostate Cancer Patients

Interventions

Type	Name	Description
DRUG	Treatment arm: TSL2109 capsules。Oral administration。	Dosage and Administration: Oral administration on an empty stomach, once daily. Applicable to 50mg (2 capsules of 25mg), 100mg (1 capsule of 100mg), 200mg (2 capsules of 100mg), 300mg (3 capsules of 100mg), 400mg (4 capsules of 100mg), and 500mg (5 capsules of 100mg) dose groups. Duration of Treatment: Multiple dosing, with each treatment cycle consisting of 28 days.

Timeline

• Start date: 2026-02-20
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2026-04-07
• Last updated: 2026-04-07

Locations

1 site across 1 country: China