The 2025 European Society for Medical Oncology (ESMO) Congress will be held in Berlin, Germany from October 17 to 21, 2025 (local time). As one of the most influential global academic conferences in the field of oncology, the ESMO Congress attracts numerous leading experts and scholars, providing a stage to discuss clinical challenges and share cutting-edge advancements. Early clinical research results for three key drugs in TYK Medicines’ (Stock Code: 02410.HK) CDK inhibitor pipeline—TYK-00540 (CDK2/4i), TY-2699a (CDK7i), and TY-302 (CDK4/6i)—were presented in poster sessions at ESMO Congress 2025.

 

 

 Clinical Study of TYK-00540

Title: Safety and Preliminary Efficacy of a Novel CDK2/4 Inhibitor TYK-00540 in Patients with Advanced Solid Tumors. Results from a Phase I Dose-Escalation Study (FPN 505P)

Principal Investigator: Prof. Jian Zhang, Fudan University Shanghai Cancer Center

Background:
CDK4/6 inhibitors (CDK4/6i) have become the cornerstone of first-line treatment for HR+/HER2- advanced breast cancer (BC), but resistance is inevitable. Preclinical studies have shown that resistance to CDK4/6i can be overcome by concomitant inhibition of CDK2. Therefore, simultaneous inhibition of CDK2/4 may represent a promising strategy to improve clinical outcomes. TYK-00540 is a novel CDK2/4 inhibitor developed for the treatment of HR+/HER2- BC resistant to CDK4/6i. This first-in-human, dose-escalation Phase I study (NCT06950086) aimed to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of TYK-00540 in patients with advanced solid tumors.

Methods:
This Phase I study consisted of a monotherapy dose-escalation phase (Part 1), a combination dose-selection phase (with fulvestrant, Part 2), and a dose-expansion phase (Part 3). Part 1 enrolled patients with HR+/HER2- mBC, triple-negative breast cancer (TNBC), ovarian cancer (OC), and non-small cell lung cancer (NSCLC), who were then treated with TYK-00540 monotherapy. Part 2 enrolled patients with HR+/HER2- mBC and treated with TYK-00540 combined with fulvestrant. Part 3 assigned patients with HR+/HER2- BC and OC to four cohorts based on cancer type, prior endocrine therapy, and previous exposure to CDK4/6i, providing either TYK-00540 monotherapy or in combination with fulvestrant.

Results:

Baseline Characteristics: As of July 15, 2025, 24 patients were enrolled in the monotherapy dose-escalation phase, of whom 16 had received prior CDK4/6i therapy. This cohort included 15 patients with HR+/HER2- breast cancer, all of whom had received prior endocrine therapy and at least one prior CDK4/6i.

Safety: Among the 24 patients, Grade 3 or higher (≥G3) treatment-related adverse events (TRAEs) occurred in 11 (45.8%), and ≥G3 treatment-related serious adverse events (TRSAEs) occurred in 2 (8.3%) patients. The most common TRAE were primarily hematologic toxicities, as well as nausea and vomiting, which were manageable with treatment interruption. No treatment discontinuations or deaths due to TRAE.

Efficacy: Among the 13 evaluable patients with HR+/HER2- BC, 2 achieved a confirmed partial response (PR) and 5 achieved stable disease (SD). This resulted in an objective response rate (ORR) of 15.4% (2/13) and a disease control rate (DCR) of 53.8% (7/13).

PK Profile: TYK-00540 exhibited a dose-proportional increase in exposure, rapid absorption (T_max=1~4h), a suitable terminal half-life (t_1/2=3.98~5.67h), and minimal accumulation observed at different doses.

Conclusions:

• TYK-00540 monotherapy showed hematological toxicity as the main adverse reaction, which resolved effectively after treatment interruption or intervention, demonstrating an overall manageable safety profile. Encouraging efficacy was observed in heavily pretreated patients with HR+/HER2- mBC who were resistant to CDK4/6i. Based on the safety and efficacy data, 30mg Bid was determined as the recommended dose for expansion (RDE).
• The study of TYK-00540 in combination with fezolinetant (NCT06950086) is ongoing, with the expectation of further addressing the unmet clinical needs of these patients.

 

The latest clinical data show that among 6 evaluable patients with platinum-resistant OC treated with TYK-00540 monotherapy, the ORR and DCR were were 20% (1/5）and 60% (3/5). Among 3 evaluable patients with HR+/HER2- BC treated with TYK-00540 in combination with Fulvestrant, the ORR and DCR were 33.3% (1/3) and 100% (3/3).

 

Clinical Study of TY-2699a

Title: A Phase I Dose-Escalation Study of TY-2699a, a non-Covalent Inhibitor of CDK7, in Patients with Advanced Solid Tumors (FPN 975P)

Principal Investigator: Acad. Binghe Xu, Chinese Academy of Medical Sciences and Peking Union Medical College National Cancer Center, Cancer Hospital

Background: CDK7 plays a critical role in regulating cell cycle progression, transcription, and nuclear receptor activity, positioning CDK7i as a promising novel anti-tumor strategy. TY-2699a is a selective, non-covalent, oral CDK7i. Here, we report preliminary results from a Phase I study (NCT05866692), focusing on the safety, tolerability, and PK profile of a twice-daily (BID) dosing schedule within a 28-day treatment cycle.

Key Findings: This Phase I study utilized a Bayesian Optimal Interval (BOIN) design. 20 patients with advanced solid tumors were enrolled across five dose-escalation cohorts. Results demonstrated that continuous BID dosing of TY-2699a achieved high exposure levels with a manageable safety profile and showed preliminary anti-tumor activity. SD was observed in 3 patients: one with TNBC in the 5 mg cohort, and one each with HR+/HER2- mBC in the 20mg and 30mg cohorts; these patients remain on treatment. Further study in intermittent regimens and combinations is warranted.

 

 

 

Clinical Study of TY-302 Combined with Toremifene

Title: TY-302, a CDK4/6 inhibitor, combined with toremifene in patients with advanced solid tumors. Results from a phase Ia/Ib study (FPN 513P)

Principal Investigators: Acad. Binghe Xu/Prof. Fei Ma, Chinese Academy of Medical Sciences and Peking Union Medical College National Cancer Center, Cancer Hospital

Background: TY-302 is a potent, selective CDK4/6i in development for advanced solid tumors, including breast and prostate cancer. TY-302 targets the key cell cycle regulators CDK4/6, inhibiting retinoblastoma (Rb) protein phosphorylation and consequently suppressing cancer cell proliferation. TY-302 is currently the only CDK4/6i among numerous CDK candidates that is suitable for prostate cancer. Here, we report the safety, PK profile, and preliminary efficacy results of TY-302 combined with toremifene in patients with advanced BC from this first-in-human phase Ia/Ib study (NCT04433494).

Key Findings: Results of the phase I study showed that TY-302 (100 mg QD) combined with toremifene exhibited promising anti-tumor activity and manageable toxicity in patients with HR+/HER2- mBC. Grade ≥ 3 AEs were primarily hematologic toxicities. Among 31 evaluable HR+/HER2- mBC patients treated with TY-302 (100 mg) plus toremifene, the ORR and DCR were 19.4% and 77.4%, respectively, with a median progression-free survival (mPFS) of 8.2 months. These results support further exploration of this regimen in this patient population.