放射治疗durvalumab和tremelimumab治疗复发性妇科癌症的I期临床试验

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2025-04-23 DOI:10.1016/j.ygyno.2025.04.006

Kelly J. Fitzgerald, Panagiotis Konstantinopoulos, Ursula Matulonis, Joyce Liu, Neil Horowitz, Elizabeth Lee, David L. Kolin, Larissa Lee, Martin King

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引用次数: 0

摘要

目的探讨双免疫检查点阻断（ICB）与姑息放疗（RT）协同治疗对妇科复发/转移癌患者的疗效。我们进行了一项开放标签前瞻性I期试验，以评估ICB + rt的安全性和耐受性。方法复发/转移性子宫内膜癌、卵巢癌、子宫癌、阴道癌或外阴癌的患者符合条件。安全性先导队列A接受程序性死亡配体（PD-L1）抑制剂durvalumab 1500mg IV / q4周和25 Gy的姑息性放疗，分5个部分治疗单个腹腔病变。队列B还接受了4个周期的细胞毒性t淋巴细胞相关蛋白4 （CTLA-4）抑制剂tremelimumab 75mg IV。主要终点是在放疗后8周接受治疗的患者的剂量限制性毒性（dlt）率。次要终点包括未放疗病变的总缓解率（ORR）。结果16例患者入组，其中12例能够评估主要终点。队列A中零例DLTs发生，队列B中1例铂耐药卵巢癌患者有两个转移部位（在试验入组前照射的盆腔肿块和在方案中照射的腹膜结节），其疾病负担显著减轻，3年未接受任何治疗。未照射病变的ORR为0%。结论在未选择的复发性妇科恶性肿瘤患者中，联合durvalumab、tremelimumab和RT治疗单个病变的dlt有限，但对未放疗的病变无反应。1例少转移性疾病患者获得了长期持久的益处。临床试验信息：NCT03277482

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A phase I clinical trial of radiation therapy, durvalumab and tremelimumab in recurrent gynecologic cancer

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A phase I clinical trial of radiation therapy, durvalumab and tremelimumab in recurrent gynecologic cancer

Objective

Dual immune checkpoint blockade (ICB) may synergize with palliative radiotherapy (RT) to improve responses in patients with recurrent/metastatic gynecologic cancer. We conducted an open label prospective phase I trial to assess the safety and tolerability of ICB plus RT.

Methods

Patients with recurrent/metastatic endometrial, ovarian, cervical, vaginal or vulvar cancer were eligible. The safety lead-in cohort A was treated with programmed death ligand (PD-L1) inhibitor durvalumab 1500 mg IV q4 weeks and palliative RT of 25 Gy in 5 fractions to a single abdominopelvic lesion. Cohort B also received 4 cycles of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor tremelimumab 75 mg IV. The primary endpoint was the rate of dose-limiting toxicities (DLTs) in patients on protocol 8 weeks after RT. Secondary endpoints included the overall response rate (ORR) in non-irradiated lesions.

Results

16 patients were enrolled, with 12 able to be assessed for the primary endpoint. Zero DLTs occurred in cohort A and 1 in cohort B. One patient in cohort B with platinum resistant ovarian cancer with two metastatic sites (a pelvic mass irradiated prior to trial enrollment and a peritoneal nodule irradiated on protocol) had a dramatic reduction in disease burden and remains off all therapy >3 years. The ORR of non-irradiated lesions was 0 %.

Conclusions

Combining durvalumab, tremelimumab and RT to a single lesion had limited DLTs but no response in non-irradiated lesions in unselected patients with recurrent gynecologic malignancies. One patient with oligometastatic disease experienced prolonged durable benefit. Clinical trial information: NCT03277482

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来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy