TSL2109 capsules for advanced solid tumors, including treatment‑resistant prostate cancer

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

This trial tests whether the oral drug TSL2109 is safe, tolerable, and shows early signs of benefit for people with advanced solid tumors, especially those with metastatic castration‑resistant prostate cancer who have progressed after standard therapies.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tasly Pharmaceutical Group Co., Ltd (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07514065 on ClinicalTrials.gov

What this trial studies

TSL2109 is a novel oral small‑molecule that simultaneously inhibits CDK4/6 and DYRK2, designed to block tumor cell cycle progression independent of hormonal signaling. This Phase 1 interventional trial uses dose‑escalation followed by dose‑expansion cohorts to characterize safety, tolerability, pharmacokinetics, and preliminary antitumor activity. Priority enrollment is given to patients with metastatic castration‑resistant prostate cancer and HR+/HER2‑ advanced breast cancer who have exhausted standard therapies. The trial is conducted at Shanghai Gaobo Cancer Hospital and enrolls adults with ECOG 0–1 and measurable disease per RECIST 1.1.

Who should consider this trial

Good fit: Adults (≥18) with advanced solid tumors who have failed or are unsuitable for standard therapy, have life expectancy ≥3 months, and ECOG performance status 0–1—especially patients with metastatic castration‑resistant prostate cancer or HR+/HER2‑ breast cancer—are the intended candidates.

Not a fit: Patients with poor performance status (ECOG >1), life expectancy under three months, or who still have effective standard treatment options are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, TSL2109 could provide a new oral treatment option that overcomes resistance to androgen‑receptor and CDK4/6 inhibitors for patients with progressive metastatic castration‑resistant prostate cancer and some HR+/HER2‑ breast cancers.

How similar studies have performed: Selective CDK4/6 inhibitors have shown clinical benefit in HR+ breast cancer, but a dual CDK4/6‑DYRK2 inhibitor like TSL2109 is a novel approach supported so far mainly by preclinical data suggesting it may overcome resistance.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years.
2. Histologically or cytologically confirmed advanced solid tumors, with failure of prior standard therapy, or no available standard therapy, or currently unsuitable for standard therapy, and not amenable to surgery or radiotherapy with curative intent. Priority will be given to patients with metastatic castration-resistant prostate cancer (mCRPC) and HR+/HER2- advanced breast cancer.
3. (Dose-Escalation Phase) At least one evaluable or measurable tumor lesion per RECIST Version 1.1; (Dose-Expansion Phase) At least one measurable tumor lesion per RECIST Version 1.1 (tumor lesions located in prior radiation fields or other locally treated sites generally do not qualify as measurable lesions unless there is clear progression or persistence three months after radiotherapy).
4. Life expectancy ≥3 months.
5. ECOG performance status score of 0 to 1.

Metastatic Castration-Resistant Prostate Cancer (mCRPC):

Castration status at screening: (1) Currently receiving androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist or history of bilateral orchiectomy. (2) Serum total testosterone ≤1.7 nmol/L (50 ng/dL) at screening. Additionally, progression documented by one or more of the following three criteria: ① PSA progression defined as PSA \>1 ng/mL with two consecutive increases \>50% from baseline at least 1 week apart; ② Soft tissue disease progression per RECIST 1.1; ③ Bone disease progression per PCWG3, defined as two or more new bone lesions on bone scan. Priority will be given to end-line patients who have received prior androgen receptor inhibitors and have received chemotherapy or are chemotherapy-intolerant or chemotherapy-refusing.

HR+/HER2- Breast Cancer:

① Histologically or cytologically confirmed HR-positive, HER2-negative breast cancer (determined from the most recent tumor sample \[primary or metastatic\] with histological confirmation of HR+/HER2- status. To meet HR+ disease requirements, breast cancer must express estrogen receptor \[ER\], with or without progesterone receptor co-expression), locally advanced or recurrent/metastatic breast cancer in female patients. ② Prior exposure to CDK4/6 inhibitors (e.g., abemaciclib, palbociclib, etc.).

Exclusion Criteria:

1. Clinically symptomatic central nervous system (CNS) metastases or leptomeningeal metastases, or other evidence indicating uncontrolled CNS or leptomeningeal metastases, judged by the investigator as unsuitable for enrollment.
2. Diagnosis of another invasive malignancy within the past 2 years, except for radically treated non-melanomatous skin cancer or superficial urothelial carcinoma, cutaneous basal cell or squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, papillary thyroid carcinoma, cervical carcinoma in situ, or breast carcinoma in situ.
3. Clinically significant gastrointestinal dysfunction that may affect drug intake, transport, or absorption, such as inability to take oral medications, uncontrolled nausea or vomiting, history of extensive gastrointestinal resection, unresolved recurrent diarrhea, untreated gastric conditions requiring long-term proton pump inhibitor therapy, Crohn's disease, ulcerative colitis, intestinal obstruction, etc.
4. Imaging (CT or MRI) showing tumor invasion of major blood vessels (e.g., aorta, pulmonary arteries/veins, vena cava, etc.) with assessed bleeding risk.
5. Interstitial lung disease, pneumonitis, or pulmonary fibrosis, assessed by the investigator as unsuitable for enrollment.
6. History of deep vein thromboembolism.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Gaobo Cancer Hospital (China Pharmaceutical University) — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Jin Li, Doctor — Shanghai Gobroad Cancer Hospital (China Pharmaceutical University)
• Study coordinator: Rui Liu

Conditions Metastatic Castration-Resistant Prostate Cancer Patients