(P 411) PROPANE AN OPEN LABEL PHASE 2 STUDY ON PROPRANOLOL AND PEMBROLIZUMAB IN ADVANCED ANGIOSARCOMA AND UNDIFFERENTIATED PLEOMORPHIC SARCOMA A SCANDINAVIAN SARCOMA GROUP COLLABORATION

Objective: Emerging results on immune therapy based on PD-1 antagonists are promising especially in undifferentiated pleomorphic sarcoma (UPS) and angiosarcoma (AS). Targeting the neuro-tumor-immune axis by blocking beta-adrenergic receptors (BAR) with a non-selective beta-blocker has shown increased immunotherapy efficacy and survival in preclinical and retrospective clinical studies. By targeting both PD-1 and BAR, we hypothesize an additive clinical benefit in both AS and UPS patients with a tolerable adverse event profile and quality of life (QoL).
The primary objective is to determine the progression-free survival rate (PFSR) at 3 months. Secondary endpoints are objective response rate (ORR), duration of response (DOR), PFS, OS, safety, and QoL. Exploratory endpoints include characterizing the immune cells and tumor microenvironment in situ and systemically.

Methods: A single arm, Simon’s 2-stage, phase 2 study of pembrolizumab and propranolol in two separate cohorts (NCT05961761). Patients will receive pembrolizumab 2 mg/kg every 3 weeks and propranolol 40 mg b.i.d. until progression, unacceptable toxicity, or patient withdrawal for a maximum of two years. Subjects will be followed with PFS, ORR, OS, and QoL for up to 1 year after treatment.
The primary endpoint will be tested with the aim of excluding a PFS rate in 3 months of 20% (P0) or less under the alternative assumption that 40% (P1) of patients could be progression-free at 3 months, considering a type I error rate of 0.1 (one-sided) and a power of 0.9. With an estimated up to 10% inclusion error/drop out a total of up to 40 patients in each cohort is planned.

Highlighted inclusion criteria are:
• Histologically confirmed diagnosis of unresectable locally advanced or metastatic angiosarcoma or undifferentiated pleomorphic sarcoma, in patients who have progressed/failed to provide clinical benefit on first line standard chemotherapy.
• Age ≥18 years
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≤2 at the time of enrollment

Results: N/A This is a Trial In Progress

Conclusion: N/A This is a Trial In Progress