Background/Objectives:Little is known about the synergy between intratumoral immunotherapy and cancer ablation. We conducted a Phase II Trial (Abscopal 5001 trial; NCT04713371) in patients with metastatic solid cancer to assess the safety and efficacy of cryoablation with concurrent injection of RPT-01-5001 (combination of low-dose checkpoint inhibitors and cyclophosphamide), a treatment process referred to as Multiplex Intratumoral Immunotherapy (MITITM).Methods:Twelve patients with metastatic cancer who had failed standard therapy and one with sacral chordoma received at least one intratumoral treatment of MITI preceded by 3–5 days of oral low-dose cyclophosphamide. MITI consisted of CT-guided cryoablation followed by intratumoral injection of RPT-01-5001. GM-CSF was subcutaneously administered daily for four weeks. Treatment was repeated every four weeks if the tumor burden remained stable or reduced, as noted by the iRECIST criteria. These criteria were modified when follow-up biopsies revealed pathology with minimal or no cancer, despite persistent suspicious masses on imaging.Results:Cancers included prostate (four patients), sarcoma (two), and one each of breast, colon, bladder, uterine cervix, tongue, kidney, and sacral chordoma. Eight patients received three cycles of treatment, two received two, and three received one. All patients tolerated the procedure well and were discharged within 2 h. The adverse event rate was 69%, all of which were grade 1 or 2, except for two grade 3 cases with delayed cryosurgical complications (15%). At completion of up to three cycles of treatment, a complete response (iCR) was observed in one patient (7.7%), partial response (iPR) in four patients (30.8%), and stable disease (iSD) in five (38.5%), with a disease control rate (iDCR) of 77%. Disparity between post-treatment imaging and pathologic findings was observed in four patients (positive vs. negative, respectively), requiring modification of the iRECIST criteria in favor of pathology. The best response ranged from 0 to 91%, with a mean for responding patients of 38%. Median progression-free survival (PFS) and 95% confidence intervals (95% CI) were 5.4 months (1.8 to 23.1 months); and median overall survival (OS) was 20.9 months (9.1 to 22.8 months). The injection site cancer response was observed in nine (69%) patients, and the distal abscopal effect was seen in four (31%), including one sarcoma patient with a complete abscopal response of lung metastases and one bladder cancer patient with biopsy-confirmed complete resolution of lung and liver metastases.Conclusions:MITI with RPT-01-5001 is safe and highly feasible, providing 77% disease control and 31% of the abscopal effect in patients with metastatic cancer who have failed standard therapies.
背景/目的：目前关于瘤内免疫疗法与肿瘤消融术协同作用的研究尚不充分。我们针对转移性实体癌患者开展了一项II期临床试验（Abscopal 5001试验；注册号NCT04713371），旨在评估冷冻消融联合注射RPT-01-5001（低剂量检查点抑制剂与环磷酰胺的复合制剂）——该治疗方案称为多重瘤内免疫疗法（MITITM）——的安全性与有效性。 方法：12例标准治疗失败的转移性癌症患者及1例骶骨脊索瘤患者在接受为期3-5天的口服低剂量环磷酰胺预处理后，接受了至少一次MITI瘤内治疗。MITI治疗方案包括CT引导下冷冻消融术及后续的RPT-01-5001瘤内注射。所有患者每日皮下注射粒细胞-巨噬细胞集落刺激因子（GM-CSF），持续四周。根据iRECIST标准评估，若肿瘤负荷保持稳定或减轻，则每四周重复治疗周期。当随访活检显示影像学持续可疑肿块中癌组织极少或无癌组织时，我们对评估标准进行了调整。 结果：纳入的癌症类型包括前列腺癌（4例）、肉瘤（2例），以及乳腺癌、结肠癌、膀胱癌、宫颈癌、舌癌、肾癌和骶骨脊索瘤各1例。8例患者完成三个治疗周期，2例完成两个周期，3例完成一个周期。所有患者对治疗过程耐受良好，均在2小时内出院。不良事件发生率为69%，除2例（15%）出现3级延迟性冷冻手术并发症外，其余均为1-2级。在完成最多三个治疗周期后，1例患者（7.7%）达到完全缓解（iCR），4例（30.8%）达到部分缓解（iPR），5例（38.5%）疾病稳定（iSD），疾病控制率（iDCR）达77%。4例患者出现治疗后影像学与病理学结果不一致（分别为阳性与阴性），需根据病理结果调整iRECIST标准。最佳缓解率范围为0-91%，应答患者的平均缓解率为38%。中位无进展生存期（PFS）及95%置信区间（95% CI）为5.4个月（1.8-23.1个月）；中位总生存期（OS）为20.9个月（9.1-22.8个月）。9例患者（69%）出现注射部位肿瘤应答，4例（31%）观察到远端旁观者效应，其中1例肉瘤患者肺转移灶完全消退，1例膀胱癌患者经活检证实肺及肝转移灶完全消失。 结论：RPT-01-5001联合MITI治疗方案安全可行，为标准治疗失败的转移性癌症患者提供了77%的疾病控制率及31%的旁观者效应。
肿瘤(癌症)患者之家