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

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.