Phase I/II study to evaluate penpulimab combined with anlotinib and epirubicin in the first-line treatment of soft tissue sarcoma: Updated.
Authors: Zhou Yuhong , Li Wei , Fang Meiyu , Zhuang Rongyuan , Feng Yi , Guo Xi , You Yang , Zhang Chenlu , Song Zhengqing , Ding Yuqin , Wang Zhiming , Luo Rongkui , Fan Zhengfu , Tong Hanxing , Zhang Yong , Lu Weiqi 
Published: June 2023

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Background: Anthracycline-based chemotherapy regimens are the cornerstone of first-line treatment of recurrent/metastatic unresectable soft tissue sarcoma(STS)，while the efficacy was not satisfactory (the median PFS: 4-8 months). Anti -angiogenesis TKI hypothetically can improve the efficacy of chemotherapy by remodeling the immunosuppressive TME. We conducted this trial to explore the safety and efficacy of PD-1 antibody Penpulimab(P) plus anlotinib(A) and epirubicin(E) in the first-line treatment of STS. The results of the phase I study were reported (2022 ESMO), We updated the latest efficacy and safety data. Methods: This ongoing phase I/II, open-lable trial (ChiCTR2100048014) enrolled patients (pts) aged 16-75 years old with pathologically confirmed metastatic or unresectable locally advanced STS. Pathologic types are moderately sensitive or above to anthracycline chemotherapy. Pts who met the inclusion criteria were treated with phase I dose results (E 60 mg/m2 + A 10 mg and P 200 mg；E: IV, D1-3, Q3W, A: PO, QD, D1-14, Q3W, P: IV, Q3W ) for a total of 6 treatment cycles (3 weeks each). A+P was maintained for 2 years until progressive disease or unacceptable toxicity. The primary endpoint was PFS(progression-free survival ) and secondary endpoints were ORR(objective response rate), DCR(disease control), OS(overall survival), 2-year OS and PFSR at 3 and 6 months. The response to treatment was evaluated according to RECIST vesion 1.1. In addition,adverse events were evaluated by CTCAE v5.0. Results: From September 2021 to December 2022, 32 pts (14 males and 18 females) were enrolled with the median age is 53.5 (range 29-73) years old. Pathological types included liposarcoma (DDLPS 14, PLS 1, n = 15), undifferentiated sarcoma (n = 4), leiomyosarcoma (n = 5), angiosarcoma (n = 3), fibrosarcoma (n = 2), and others (n = 3). At the data cut off date on December 20, 2022, Median follow-up time was 3.5 months （range 0.03-15.38）, Median PFS was 10.55 months [95%CI 4.60, 14.59]. Median OS was not reached. The PFS at 3 months and 6 months was 86.76%, 68.16%, respectively. and the OS at 12 months was 92.64%. 24 pts were eligible for the evaluation of tumor response, the objective response rate (ORR) was 12.50% (4/24) and the disease control rate (DCR) was 68.75% (14/24). The incidence of treatment-related adverse events of grade 3 was 31.25%, with a higher incidence of hypertriglyceridemia (9.38%), Neutrophil count decreased (6.25%) , palmar-plantar erythrodysesthesia syndrome (6.25%), febrile neutropenia (6.25%), respectively. The incidence of Severity Adverse Event was 12.5%. 50 pts are expected to be enrolled in the study, and the data will be mature after the follow-up is completed. Conclusions: Penpulimab(P) plus anlotinib(A) and epirubicin(E) has shown encouraging activity as firsy-line treatment for STS, which significantly prolong the PFS with well tolerance. Clinical trial information: ChiCTR2100048014 .