ESTRO meets Asia 2024 - Abstract Book

S262

Interdisciplinary – SBRT

ESTRO meets Asia 2024

96

Proffered Paper

A novel therapy based on SBRT targeting HER-2 expression advanced solid tumors (PRaG 3.0 Regimen)

Meiling Xu, Yuehong Kong, Pengfei Xing, Junjun Zhang, Xiangrong Zhao, Liyuan Zhang

Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China

Purpose/Objective:

The effectiveness of radiotherapy, particularly stereotactic radiotherapy (SBRT), in modulating tumor phenotypes, enhancing antigen presentation, and provoking a systemic immune response has gained wide acceptance. This creates a solid foundation for combining radiotherapy with immunotherapy (iRT). The PRaG therapy, a novel iRT approach, utilizes SBRT, PD-1/L1 inhibitors, and GM-CSF to activate the immune response and alter the tumor microenvironment, aiming for an abscopal effect. Previous research has shown the PRaG regimen to be effective in treating advanced refractory tumors. RC48-ADC, an anti-HER2 antibody-drug conjugate, induces immunogenic cell death and a broad release of cancer cell antigens, thereby enhancing the effect of immunotherapy through the activation of effector T-cells. This study aims to evaluate the efficacy and safety of combining RC48-ADC with radiotherapy, PD-1/L1 inhibitors, GM-CSF, and IL-2 (PRaG3.0 regimen) in treating HER2-expressing advanced solid tumors.

Material/Methods:

This study enrolled participants with advanced, confirmed HER2-expressing (IHC3+, 2+, or 1+) solid tumors that had progressed following standard treatments or due to intolerance. During a PRaG3.0 regimen cycle, participants received RC48-ADC (2.0 mg/kg on day 1, every 3 weeks), followed by HFRT (2-3 doses of 5-8 Gy) targeting one metastatic lesion every other day. This was followed by GM-CSF (200 μg on days 3-7), sequential IL-2 (2 million IU on days 8-12), and a PD-1/L1 inhibitor administered within one week after completing HFRT. After at least 6 cycles of RC48-ADC combined with PD-1/L1 inhibitor, GM-CSF, and IL-2, maintenance therapy with a PD-1/L1 inhibitor continued until disease progression or unacceptable toxicity was observed. The primary endpoint of the study was the objective response rate (ORR). The trial's registration number is: NCT0511550.

Results:

As of January 31, 2024, 29 patients had been enrolled at this center, including 6 with gynecological tumors, 5 with pancreatic cancer, and 18 with various other types of tumors (such as breast, gastric, lung, renal, and colorectal cancers). According to RECIST 1.1 criteria, the overall objective response rate (ORR) was 41.4%, with two patients achieving complete response (CR) for nearly two years and maintaining minimal residual disease (MRD) negative status. The disease control rate (DCR) stood at 72.4%, with ORRs of 66.7% for gynecological tumors, 25.0% for pancreatic cancer, and 36.8% for other tumor types. Notably, the ORR for patients with low HER-2 expression (1+) was 47.4%, compared to 30% for those with high HER-2 expression (2+ to 3+). The median progression-free survival (PFS) for all patients was 6.3 months (95% CI: 4.5, 8.1). Treatment-related adverse events were predominantly mild (grade 2 or below), including fatigue, hair loss, nausea, fever, and rash. Only 2 patients (6.8%) experienced grade 3 side effects, which were abnormal liver function and skin itching.

Conclusion: