1731P - Phase II study of the CDK2/4/6 inhibitor TQB3616 capsules in patients with dedifferentiated liposarcomas (DDLPS)

Background

DDLPS is one of the most common types of soft tissue sarcoma (STS) arising in retroperitoneum. First line treatment is mainly systematic chemotherapy for metastatic or surgically unresectable patients. However, the role of systemic therapy is limited because DDLPS is not sensitive to chemotherapy. CDK4 is amplified in 90% of DDLPS, TQB3616 is a new CDK2/4/6 kinase inhibitor, which can selectively inhibit the activity of CDK2/4/6 protein kinase and has potential efficacy in the treatment of dedifferentiated liposarcoma.

Methods

This multicenter study include two phases of single-arm and randomized, double-blind, placebo-controlled trial. In single-arm phase, patients with metastatic or surgically unresectable DDLPS were included. The primary endpoint was 12-week PFS rate, secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Patients received dose of TQB3616 180mg/QD, every 4 weeks in a treatment cycle. Efficacy was evaluated according to RECIST 1.1 evaluation criteria.

Results

As of Apr. 5th, 2024, 26 patients have been enrolled, 23 patients can be evaluated for efficacy. The number of prior systemic therapy range from 0 to 2.Preliminary efficacy results showed 12-weeks PFS rate was 63.6% (90% CI, 40.0% ∼79.9%), ORR was 8.7% (2/23), DCR was 78.3% (18/23), the median PFS was 4.7 months (95% CI, 2.07∼15.57), the median OS was not obtained (95% CI, 7.82 ∼), but 12 month OS rate was 66.5%(90% CI, 39.0% ∼ 83.7%). There are seven patients still continue to receive treatment, and six of them have been treated for more than 12 months. Regarding safety, grade ≥3 treatment related adverse events (TRAEs) occurred in 30.8% (8/26) of patients, the most common events involved neutropenia (19.2%, 5/26), leukopenia (11.5%, 3/26), thrombocytopenia (7.7%, 2/26), alanine aminotransferase increased (3.8%, 1/26) and vomiting (3.8%, 1/26). 7.7% (2/26) of patients occurred dose reduction because of TRAEs.

Conclusions

CDK2/4/6 inhibitor TQB3616 has shown therapeutic potential in DDLPS. Based on the good efficacy and safety of single-arm part, the randomized, double-blind part has been approved by National Medical Products Administration (NMPA).

Clinical trial identification

NCT05496569.

Editorial acknowledgement

Funding

Chia Tai Tianqing Pharmaceutical Group Co., LTD.

Disclosure

All authors have declared no conflicts of interest.