A Study of TY-2699a in Patients With Locally Advanced or Metastatic Solid Tumors

Inclusion Criteria: 1. Be able to provide written informed consent approved by institutional review board (IRB) or independent ethics committee (IEC). 2. Age ≥18 years. 3. At the escalation stage, patients should fulfill the following criteria at Screening: 1\) Participants with locally advanced or metastatic solid tumors including TNBC, ER+HER2-BC, ovarian cancer, small cell lung cancer, castrate-resistant prostate cancer (CRPC), or PDAC with KRAS mutant; Or any other locally advanced or metastatic solid tumor with evidence of deregulated RB-pathway based on available molecular test results and after sponsor review to confirm eligibility as determined with prior molecular assays performed in a CLIA-certified or equivalent laboratory. (Note: ① 0% - 1% of tumor cells expressing ER or PR as negative while ≥ 1% of tumor cells expressing ER or PR as positive on IHC staining, recommended by ASCO/CAP guideline Update 2020; negative HER2 is defined as IHC 0 or 1+, or IHC 2+ but confirmed by the negative ISH, recommended by ASCO/CAP Guideline 2018; ② Genes of KRAS and other biomarkers will be detected by the Polymerase Chain Reaction (PCR) or Next-Generation Sequencing (NGS)); 2) Patients who have progressed on established standard medical anti-cancer therapies for a given tumor type or have been intolerant to such therapy, or in the opinion of the investigator have been considered ineligible for a particular form of standard therapy on medical grounds. 4\. At the expansion stage, patients should fulfill the following criteria at Screening : 1)Cohort : TNBC patients progressed on ≥ 2 previous lines of therapy and/or other solid tumors will receive TY-2699a. ① Previous therapy can be of any nature (chemotherapy, immunotherapy, antiangiogenics, experimental therapy, etc.); ② Histologically-confirmed breast carcinoma not expressing ER, PR, and HER2 (negative ER and PR is defined as \< 1% tumor cells expressing ER and PR on IHC staining, recommended by ASCO/CAP Guideline Update 2020; negative HER2 is defined as IHC staining 0 or 1+ , or IHC 2+ but confirmed by the negative ISH, recommended by ASCO/CAP Guideline 2018; negative HER2 is defined as IHC 0 or 1+, or IHC 2+ but confirmed by the negative ISH, recommended by ASCO/CAP Guideline 2018); ③ With or without BRCA mutation. 5\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and life expectancy \> 3 months. 6\. Capability to swallow intact capsule (without chewing, crushing or opening). 7. At least 1 measurable target lesion according to Response Evaluation Criteria in Solid Tumor Version 1.1 (RECIST v1.1, Appendices 15.2 RECIST v1.1 ) determined by the investigator. 8\. All acute toxic effects (excluding alopecia and neuropathy associated with prior platinum-based drug therapy) of any prior therapy recovered to grade ≤1 based on NCI CTCAE v5.0. 9\. Baseline laboratory results fulfilling the following requirements: Absolute neutrophils count (ANC) ≥1500/mm3 (1.5×109/L) \* Platelets ≥100,000/mm3 (100×109/L) \* Hemoglobin \> 90 g/L\* Estimated creatinine clearance ≥55 mL/min+ Total serum bilirubin \<1.5 × ULN \<3.0 × ULN if known Gilbert's disease Liver transaminases (AST/ALT) \<2.5 × ULN; \<5 × ULN if liver metastases are present ULN: upper limit normal. * No blood transfusion, blood products, or hematopoietic factors such as G-CSF, erythropoietin or albumin within 14 days prior to first dose. * Cockcroft-Gault Equation. 10. For female patients of childbearing potential, the serum or urine pregnancy test within 7 days prior to the start of TY-2699a treatment should be negative. 11\. Male and female patients of childbearing potential must agree to use at least two method of highly effective contraception from signing ICF, throughout the study and continued for 90 days after the last dose of TY-2699a treatment at the escalation stage or for the labeled duration of contraception of the combined approved drug fulvestrant (e.g., FASLODEX requires one-year contraception after the last dose) or PD-L1 antibody (will decide a brand approved in US before starting expansion stage) after the last dose at the expansion stage. 12\. Willing and able to comply with all aspects of the protocol. Exclusion Criteria: 1. Concurrent participation in another interventional clinical trial, unless the patient at long-term follow-up period. 2. Patients with the following treatment: 1. Received undergone major surgery (except minor surgery such as appendicitis, tumor biopsy, etc.) within 4 weeks prior to the first dose. 2. Received bone marrow (equal to area of pelvis) or extensive radiation therapy within 28 days prior to the first dose; received local radiation therapy (e.g., thoracic spine and rib radiation therapy) within 7 days prior to the first dose of the study drug. 3. Received CYP3A and CYP2C8 strong inducers/strong inhibitors or p-gp glycoprotein inhibitors within 14 days prior to the first dose (see Appendices 15.3 Examples of CYP450-related Drugs/food). 4. History of proton pump inhibitors (PPIs) within 4 days prior to the first dose of TY-2699a; OR history of histamine H2 blockers within 2 days prior to the first dose of TY-2699a. Patients who are receiving and require continuation of drug therapy during the study with drugs known to prolong the QTc interval or that may cause torsades de pointes. 5. Prior exposure to transcriptional kinase family CDK inhibitors, such as the CDK7 and CDK9 inhibitors SY-5609，CT-7001，Alvocidib，Dinaciclib，Seliciclib and SY-1365. Exception: Previous exposure to cell cycle CDK inhibitors such as inhibitors of CDK4 and CDK6 (ie, palbociclib) is allowed. 3. History of other previous cancer (except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected), requiring therapy within the previous 5 years 4. Patients with unstable brain metastases: Patients with CNS complications requiring urgent neurosurgical treatment (e.