1498P - Phase I/II study to evaluate penpulimab combined with anlotinib and epirubicin in the first-line treatment of soft tissue sarcoma: Phase I dose escalation results

Background

Anthracycline-based chemotherapy regimens are the cornerstone of first-line treatment of recurrent/metastatic unresectable soft tissue sarcoma(STS). Anlotinib is a multi-targeted tyrosine kinase inhibitor with confirmed efficacy in STS. Penpulimab is a new type of anti-PD-1 monoclonal antibody. We conducted this trial to explore the safety and efficacy of Penpulimab(P) plus anlotinib(A) and epirubicin(E) in the first-line treatment of STS. Here we reported the results of the phase I study.

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. There were three combination cohorts(Cohort 1: E 60 mg/m² + A 10mg + P 200mg, Cohort 2: E 90 mg/m² + A 10mg + P 200mg, Cohort 3: E 90 mg/m² + A 12mg + P 200mg, E: IV, D1-3, Q3W, A: PO, QD, D1-14, Q3W, P: IV, Q3W), based on a 3+3 trail. The primary objective of the Phase I study was to determine the safety and tolerability of the treatment combination, with dose-limiting toxicity (DLT) in 21 days defining the maximum tolerated dose (MTD).

Results

Enrollment opened in Sep 2021 and data cutoff in Apr 2022. 8 pts were treated in Phase I study.(Cohort 1: n=3; Cohort 2: n=5). All pts were not given prophylactic granulocyte colony-stimulating factor(G-CSF). The median follow-up was 4.7 months (1-7 months). No DLTs were reported in Cohort 1. 2/5 pts had DLTs in Cohort 2(Grade[G] 4 febrile neutropenia). Cohort 1 was defined as the MTD and the recommended phase 2 dose(RP2D). G3 and G4 adverse events were neutrophil count decreased(3/8; 37.5%), febrile neutropenia(2/8, 25%), white blood cell decreased(2/8, 25%), hypertriglyceridemia(1/8, 12.5%), anemia(1/8, 12.5%) and hyperthyroidism (1/8; 25%). Of 7 pts evaluable for tumor response, 3 pts achieved PR, 4 pts achieved SD, the ORR was 42.9% (3/7) and the DCR was 100%(7/7).

Conclusions

RP2D was E 60 mg/m² plus A 10mg and P 200mg. High-dose epirubicin(90 mg/m²) requires prophylactic G-CSF to reduce foreseeable hematologic toxicity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.