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Soft Tissue Sarcoma

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Fluzoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Fluzoparib in combination with Dalpiciclib

Drug Fluzoparib 100mg bid PO qd, administered continuously until disease progression, unacceptable toxicity or death. 28 days as a treatment cycle.

Other names: SHR-3162

Drug Dalpiciclib 100mg/125mg/150mg PO qd, administered only from day1 to day 21 every cycle until disease progression, unacceptable toxicity or death. 28 days as a treatment cycle.

Other names: SHR-6390

Fluzoparib+ Dalpiciclib

Jin Wang, MD

wangjinr@sysucc.org.cn Wang, MD

This is a single-center, single-arm phase Ib / II clinical trial, which was included with two phase. The main purpose of the phase Ib part was to determine the dose-limiting toxicity ( DLT ), maximum tolerated dose ( MTD ), and recommended dose ( RP2D ) of Fluzoparib combined with Dalpiciclib in patients with locally advanced or metastatic sarcoma. The phase II part is mainly to observe the efficacy and safety of Fluzoparib combined with Dalpiciclib.

The overall prognosis for patients with soft tissue sarcoma is not ideal, with a median survival rate of only about 20 months for patients diagnosed with metastasis. Soft tissue sarcomas (more than 50%) are deficient in HRR due to the presence of BRCA mutations in the tumor. When patients with BRCA1/2 gene mutation are treated with PARP inhibitors, a damage to DNA single strand breaks can be observed, and cannot be repaired promptly, resulting in tumor cell death. In addition, selective inhibition of CDK4/6 was found to inhibit the growth of sarcoma cells and induce their apoptosis. For example, inhibition of CDK4 decrease the proliferation of osteosarcoma cells and promote their apoptosis in vitro, and targeted CDK6 inhibition can inhibit the proliferation, invasion and migration of Ewing's sarcoma cells. Therefore, in this study, Dalpicicli, a CDK4/6 inhibitor, and Fluzoparib, a PARP inhibitor, were used in the treatment of advanced and metastatic soft tissue sarcoma, so as to explore the efficacy and safety of the combined regimen.

Phase Ib/II Study of Fluzoparib in Combination With Dalpiciclib in Patients With Locally Advanced or Metastatic Sarcoma

A Single-center, Prospective, Single-arm Phase Ib/II Clinical Study on the Efficacy and Safety of Fluzoparib Combined With Dalpiciclib in the Treatment of Locally Advanced or Metastatic Sarcoma r

Determination of Recommended Phase II dose (RP2D) of Escalating Dose of Fluzoparib with Dalpiciclib.

Observe the incidence of dose limiting toxicity (DLT).

Determination of maximize toxicity dose(MTD)

Objective Response Rate(CR+PR), defined as best overall response (complete or partial response) across all assessment time points, determined using RECIST v1.1 criteria.

Disease control rate(DCR) is defined DCR=CR+PR+SD/CR+PR+SD+PD, which reflects the ratio of patients whose tumors shrank or remained stable for a certain period of time.

Duration of remisson(DoR) is defined as the time interval from the beginning of the response ( when CR or PR is first determined ) to progression or death ( whichever occurs first ).

Progression Free Survival is defined as from the date of first administration to the date of disease progression or death, no matter which is earlier.

Overall survial(OS) is defined as from the date of first administration to the date of death.

Adverse events defined according to Common Terminology for Adverse Events (CTCAE) v5.0

Spots Global Cancer Trial Database for fluzoparib+ dalpiciclib